1,721,008 research outputs found

    Neuroprotective effects mediated by dopamine receptor agonists against malonate-induced lesion in the rat striatum

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    In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study we used the malonate model to explore the neuroprotective potential of dopamine agonists. Rats were injected intraperitoneally with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to intrastriatal injection of malonate. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher drug concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy

    Dopamine receptor agonists mediate neuroprotection in malonate-induced striatal lesion in the rat

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    Mitochondrial bioenergetic defects are involved in neurological disorders associated with neuronal damage in the striatum, such as Huntington's disease and cerebral ischemia. The striatal release of neurotransmitters, in particular dopamine, may contribute to the development of the neuronal damage. Recent studies have shown that dopamine agonists may exert neuroprotective effects via multiple mechanisms, including modulation of dopamine release from nigrostriatal dopaminergic terminals. In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study, we used the malonate model to explore the neuroprotective potential of dopamine agonists. Sprague-Dawley rats were injected systemically with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to malonate intrastriatal insult. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy. © 2002 Elsevier Science (USA)

    Blockade of subthalamic glutamatergic activity corrects changes in neuronal metabolism and motor behavior in rats with nigrostriatal lesions

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    We infused - for four weeks - a selective antagonist of the NMDA receptor, MK-801, into the subthalamic nucleus of rats bearing an evolving nigrostriatal lesion. The aim was to block the subthalamic overactivity resulting from the dopaminergic striatal denervation. The nigrostriatal lesion caused metabolic activation - increased activity of the mitochondrial enzyme succinate dehydrogenase - of basal ganglia nuclei, ipsilaterally to the lesion, along with contralateral rotational behavior. These phenomena were effectively counteracted by the blockade of glutamatergic transmission at the subthalamic level. Pharmacological manipulation of the STN, through selective drugs capable of modulating glutamatergic transmission, may therefore represent a valuable tool for the treatment of PD

    Cognitive and affective status in mild hypothyroidism and interactions with L-thyroxine treatment

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    Objectives - While clinical hypothyroidism is associated with frank neuropsychological and affective alterations and is considered one of the causes of reversible dementia, the occurrence of these alterations and their treatment in mild hypothyroidism (MH) remains a controversial issue. Our aim was therefore to evaluate cognitive and psychological functions in a selected population of recently-diagnosed MH patients with minor subjective symptoms. Materials and methods - Thirty-six MH women (mean age 51.9 +/- 13.5 years) were observed after a careful assessment had excluded subjects with neurological, psychiatric and/or somatic disorders, or confounding conditions. The subjects were evaluated for thyroid function and tested with an extensive battery of neuropsychological tests and psychological rating scales, in basal conditions and after 6 months of L-thyroxine treatment. Results - Baseline neuropsychological performance was within the normal range, while an age-dependent reduction was found in attentive function. After L-thyroxine treatment, an increase in serum fT4 was detected in parallel with thyroid stimulating hormone (TSH) reduction. Verbal fluency and depression scores showed a slight improvement. A positive correlation was found between TSH reduction and improved mood scores. Conclusion - From the analysis of the results, treatment of asymptomatic MH would seem advisable in order to re-set hormonal levels and, particularly in older subjects, to protect the brain against the potential risk of cognitive and affective dysfunctions.Objectives - While clinical hypothyroidism is associated with frank neuropsychological and affective alterations and is considered one of the causes of reversible dementia, the occurrence of these alterations and their treatment in mild hypothyroidism (MH) remains a controversial issue. Our aim was therefore to evaluate cognitive and psychological functions in a selected population of recently-diagnosed MH patients with minor subjective symptoms. Materials and methods - Thirty-six MH women (mean age 51.9 ± 13.5 years) were observed after a careful assessment had excluded subjects with neurological, psychiatric and/or somatic disorders, or confounding conditions. The subjects were evaluated for thyroid function and tested with an extensive battery of neuropsychological tests and psychological rating scales, in basal conditions and after 6 months of L-thyroxine treatment. Results - Baseline neuropsychological performance was within the normal range, while an age-dependent reduction was found in attentive function. After L-thyroxine treatment, an increase in serum fT4 was detected in parallel with thyroid stimulating hormone (TSH) reduction. Verbal fluency and depression scores showed a slight improvement. A positive correlation was found between TSH reduction and improved mood scores. Conclusion - From the analysis of the results, treatment of asymptomatic MH would seem advisable in order to re-set hormonal levels and, particularly in older subjects, to protect the brain against the potential risk of cognitive and affective dysfunctions. © Blackwell Munksgaard 2004

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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