Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET and microdialysis

BACKGROUND: [(18) F]fluorodopa (FDOPA) positron emission tomography (PET) allows assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's disease. We examined how [(18) F]FDOPA PET-derived kinetic parameters relate the dopamine (DA) and DA metabolite content of extracellular fluid measured by microdialysis to aid in the interpretation of data from both techniques. METHODS: [(18) F]FDOPA PET imaging and microdialysis measurements were performed in unilaterally 6-hydroxydopamine-lesioned rats (n = 8) and normal control rats (n = 3). Microdialysis testing included baseline measurements and measurements following acute administration of LDOPA. PET imaging was also performed using [(11)C]dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine transporter marker and allowed assessment of denervation severity. RESULTS: The different methods provided highly correlated data. Lesioned rats had reduced DA metabolite concentrations ipsilateral to the lesion (p < 0.05 compared to controls), with the concentration being correlated with FDOPA's effective distribution volume ratio (EDVR; r = 0.86, p < 0.01) and DTBZ's binding potential (BP(ND); r = 0.89, p < 0.01). The DA metabolite concentration in the contralateral striatum of severely (>80%) lesioned rats was lower (p < 0.05) than that of less severely lesioned rats (<80%) and was correlated with the ipsilateral PET measures (r = 0.89, p < 0.01 for BP(ND)) but not with the contralateral PET measures. EDVR and BP(ND) in the contralateral striatum were not different from controls and were not correlated with the denervation severity. CONCLUSIONS: The demonstrated strong correlations between the PET and microdialysis measures can aid in the interpretation of [(18) F]FDOPA-derived kinetic parameters and help compare results from different studies. The contralateral striatum was affected by the lesioning and so cannot always serve as an unaffected control

Liquid Xenon Detectors for Positron Emission Tomography

PET is a functional imaging technique based on detection of annihilation photons following beta decay producing positrons. In this paper, we present the concept of a new PET system for preclinical applications consisting of a ring of twelve time projection chambers filled with liquid xenon viewed by avalanche photodiodes. Simultaneous measurement of ionization charge and scintillation light leads to a significant improvement to spatial resolution, image quality, and sensitivity. Simulated performance shows that an energy resolution of <10% (FWHM) and a sensitivity of 15% are achievable. First tests with a prototype TPC indicate position resolution <1 mm (FWHM).Comment: Paper presented at the International Nuclear Physics Conference, Vancouver, Canada, 201

Is axonal degeneration a key early event in Parkinson’s disease?

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of IOS Press for personal use, not for redistribution. The definitive version was published in Journal of Parkinson's Disease 6 (2016): 703-707, doi:10.3233/JPD-160881.Recent research suggests that in Parkinson’s disease the long, thin and unmyelinated axons of dopaminergic neurons degenerate early in the disease process. We organized a workshop entitled ‘Axonal Pathology in Parkinson’s disease’, on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing the state-of-the-art and defining key gaps in knowledge. A group of eight research leaders discussed new developments in clinical pathology, functional imaging, animal models, and mechanisms of degeneration including neuroinflammation, autophagy and axonal transport deficits. While the workshop focused on PD, comparisons were made to other neurological conditions where axonal degeneration is well recognized

Novel agmatine derivatives in Maerua edulis with bioactivity against Callosobruchus maculatus, a cosmopolitan storage insect pest

Food security in developing countries is threatened by crop pests and ectoparasites in livestock. Strategies for their management still rely on synthetic pesticides which are not always effective and the active ingredients persist in the environment with negative consequences for beneficial arthropods, farmers and consumers, hence necessitating research on sustainable alternatives. Botanical insecticides are increasingly relevant, typically having lower impacts on users, consumers and the environment. One example is the southern African shrub the Blue bush-berry, Maerua edulis. Recent work reported effective pest control using this plant species against cattle ticks, storage beetles and vegetable pests. However, little is known about the chemistry underlying activity and this is essential to optimize its use. Here, we identified two novel plant chemical tructures, the E and Z isomers of cinnamoyl-4-aminobutylguanidine along with the E and Z isomers of 4-hydroxycinnamoyl-4-aminobutylguanidine in the leaves of M. edulis. We isolated these compounds from the leaves and elucidated their chemical structures using various spectroscopic techniques including High Resolution Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. We also identified a further 11 closely related structures of which 6 are tentatively reported here for the first time. Stachydrine and 3-hydroxystachydrine were also identified in the leaf extract, and occurred at very high concentrations; up to 2% w/w of dry leaves. We tested these two compounds, along with the 4 main cinnamoylamides and the crude M. edulis leaf extract against the cowpea bruchid Callosobruchus maculatus at concentrations equivalent to those present in extracts used by smallholder farmers. Mortality of insects exposed to crude plant extracts after 72 h was significantly higher than the untreated control although still lower than for insects exposed to rotenone, the positive control. The two new compounds and stachydrine showed similar activity to the crude extracts suggesting that these compounds explained the activity of the extract. After 6 days, the mortality of insects exposed to crude extracts and isolated compounds was similar to that recorded with the positive control. The stachydrine fraction and the E and Z isomers of cinnamoyl-4-aminobutylguanidine also inhibited oviposition activity in fecund female beetles. Our data show that methanol extracts of M. edulis were toxic to C. maculatus and inhibited oviposition even at 0.1% w/v so these foliar chemicals may explain the activity of the plant material. We also synthesized the amides which facilitated structural elucidation, produced adequate quantities for testing and demonstrated the potential for commercial synthesis

Dystonia and paroxysmal dyskinesias: under-recognized movement disorders in domestic animals? A comparison with human dystonia/paroxysmal dyskinesias.

Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals

Sprecherverteilung, Handlungsverlauf und Aufführung des Kyklops von Euripides

(a) Remarks on the indications of the speaker in the manuscripts of Euripides’ Cyclops. (b) Analysis of action and theatrical performance in this satyr play

Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy

Altres ajuts: We thank Fundació Marató TV3 (110533), Catalunya, Spain, Comisión Sectorial de Investigación Científica (CSIC-UDELAR), Uruguay, Agencia Nacional de Investigación e Innovación (ANII), Uruguay, PEDECIBA, Uruguay, FOCEM (MERCOSUR Structural Convergence Fund), COF 03/1111 (to H.P. and M.L.N.), and Genoma España (Project GENAME, to R.J.Y.-M.) for financial support. A.V. received support from Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina, with assistance from the European Regional Development Fund. A.V. has been distinguished with an ICREA ACADEMIA award.Traumatic brain injury (TBI) remains as one of the leading causes of mortality and morbidity worldwide and there are no effective treatments currently available. Gene therapy applications have emerged as important alternatives for the treatment of diverse nervous system injuries. New strategies are evolving with the notion that each particular pathological condition may require a specific vector. Moreover, the lack of detailed comparative studies between different vectors under similar conditions hampers the selection of an ideal vector for a given pathological condition. The potential use of lentiviral vectors versus several modular protein-based nanovectors was compared using a controlled cortical impact model of TBI under the same gene therapy conditions. We show that variables such as protein/DNA ratio, incubation volume, and presence of serum or chloroquine in the transfection medium impact on both nanovector formation and transfection efficiency in vitro. While lentiviral vectors showed GFP protein 1 day after TBI and increased expression at 14 days, nanovectors showed stable and lower GFP transgene expression from 1 to 14 days. No toxicity after TBI by any of the vectors was observed as determined by resulting levels of IL-1β or using neurological sticky tape test. In fact, both vector types induced functional improvement per se