1,721,272 research outputs found
Selegiline for Treating Parkinson’s Disease
No full textBiogenic amine turnover employs the enzymes catechol-O-methyltransferase and monoamine oxidase in neuronal and glial cells. Inhibition of these enzymes elevates biogenic amine levels in the synaptic cleft. Selegiline is a selective, irreversible monoamine oxidase-B inhibitor. Its gastrointestinal absorption is fast, the maximum concentration is reached within 1 h. Main metabolites of selegiline are desmethylselegiline, methamphetamine and L-amphetamine. Symptomatic benefits of selegiline on motor symptoms in patients with Parkinson’s disease are weak. Intervals and severity of off-periods reduce after addition of selegiline, in particular during chronic levodopa intake. Selegiline increases life expectancy in levodopa-treated patients. Selegiline is administered once or twice daily, in 5 mg tablets up to 10 mg, mostly 7.5 mg. Selegiline long-term trials demonstrate, in summary, that combination of selegiline and levodopa may provide a greater clinical benefit and less progression than levodopa alone, even when levodopa without selegiline is taken at substantially higher doses
TCM Substances in Neuropsychopharmacotherapy: Basic Aspects with a Focus on Depression
No full textDepression is one of the most common complexes of heterogeneous psychiatric disorders. Etiopathogenic factors of depression are deregulation of serotonin, noradrenaline and dopamine systems, increased activity of type A monoamine oxidase, deficit of brain-derived neurotrophic factor, and impaired neurogenesis in the hippocampus and neuroinflammation. Current antidepressant medicines, such as tricyclic antidepressants, selective serotonin, or noradrenaline reuptake inhibitors and monoamine oxidase inhibitors, are effective, but about one-third of the patients are resistant to the therapy. Traditional Chinese medicine, herb, and plant-derived phytochemicals are proposed as alterative therapeutic agents in depression. This review presents molecular mechanisms underlying antidepressant effects of diet habits, traditional herbs, St John’s wort, saffron, passion flower, lavender, valerian, kava, and Ginkgo biloba, and their phytochemical constituents. Phytochemicals have been proved to modify multiple pathogenic factors of depression and ameliorate the symptoms in preclinical models. The epidemiological and clinical intervention studies have presented some beneficial effects of herb and phytochemicals. However, the intensive rapid metabolism and poor bioavailability in the brain prevent the clinical application of phytochemicals. Synthesis of more effective and stable compounds based on phytochemical scaffold and establishment of effective delivery systems are discussed in order to develop novel therapeutic strategy for depressive disorders by use of phytochemicals.<br/
The N-methyl-D-aspartate receptor channel blocker amantadine does not cause histopathological alterations in human brain tissue
No full textLow doses of N-methyl-d-aspartate (NMDA)-type glutamate receptor antagonists induce morphological alterations in neurons of the cingulate gyrus and retrosplenial cortex of the rat. Neuronal cell death may result at higher doses. These effects are a major concern with regard to the introduction of new NMDA receptor antagonists into clinical trials. Amantadine is an uncompetitive NMDA receptor antagonist, which has been in clinical use for many years. In the present study we have looked for possible morphological alterations like necrosis in postmortem human brain tissue of patients previously treated with amantadine. Formalin-fixed tissue samples were taken from the hippocampus, cingulate gyrus, and retrosplenial cortex of 8 patients on previous amantadine medication and of 11 controls. Histopathological examination of sections was performed blind. All brains except one revealed either nonspecific age-related or cerebrovascular changes or other neurodegenerative disorders including Alzheimer’s, Parkinson’s or Lewy body disease. In conclusion, histopathological examination of the hippocampus, retrosplenial cortex, and cingulate gyrus of human brain did not reveal changes suggested to be specific for previous amantadine treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Altered expression of calcium- and apoptosis-regulating proteins in multiple system atrophy Purkinje cells
No full textThe expression patterns of the calcium binding proteins calbindin and parvalbumin and of the apoptosis modulating proteins Bcl-2, Bax, and Bcl-x were studied in the cerebellum of patients with multiple system atrophy (MSA). Calbindin and parvalbumin immunoreactivity was markedly decreased in MSA Purkinje cells whereas Bax and Bcl-x protein expression was increased. Bcl-2 expression was restricted to a subpopulation of granule neurons, but no decrease of Bcl-2 was evident in MSA. Additional DNA end-labeling (ISEL) studies revealed only one possible apoptotic Purkinje cell nucleus, but nuclei in the cerebellar white matter, probably oligodendrocytes, in the cerebellum of patients with MSA. The present results suggest that a diminished calcium binding capacity of MSA Purkinje cells might lead to a change in the regulation of proteins of the bcl-2 family that could favor the pathologic initiation of apoptosis
Pharmacokinetic characterization of amantadine in human brain tissue
No full textAmantadine concentrations in human brain tissue were assessed in order to estimate population pharmacokinetic parameters using the computer program NONMEM. The elimination constant in brain tissue was determined to be 0.00447 [1/h], resulting in a t(1/2) Of 6.5 days for the mean patient in the population investigated (n = 19). An estimate of 65.5 L was obtained for the apparent volume of distribution. The elimination half-life of amantadine from brain tissue is much longer than from blood and is comparable to the previously investigated neuroleptic drugs haloperidol and levomepromazine
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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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