1,721,154 research outputs found
Adenosine A<sub>2A</sub> receptor mRNA expression in Parkinson's disease
No full textThe expression of the human adenosine A2A receptor was examined by reverse transcription polymerase chain reaction in post-mortem human brain tissue that was obtained from normal subjects and patients who died with Parkinson's disease. Adenosine A2A receptor mRNA was detected in both striatal (nucleus accumbens, caudate nucleus and putamen) and extrastriatal (globus pallidus and substantia nigra) brain regions. A significant decrease in the level of adenosine A2A receptor mRNA was found in the anterior and posterior caudate nucleus and anterior dorsal putamen, whereas a significant increase was observed in the substantia nigra pars reticulata of Parkinsonian brain when compared to age-matched controls. No change in adenosine A2A receptor mRNA levels was seen in any other brain region examined. This study demonstrates that A2A receptor mRNA expression is altered in the basal ganglia of patients who died with Parkinson's disease and who were receiving treatment with dopaminergic drugs. The adenosine A2A receptor appears subject to regulation by dopaminergic systems in human brain, though these data do not permit a distinction to be made between the effects of neuronal degeneration or drug treatment. The adenosine A2A receptor may therefore form a target for the treatment of basal ganglia disease.</p
Markers for dopaminergic neurotransmission in the cerebellum in normal individuals and patients with Parkinson's disease examined by RT-PCR
No full textThe presence of neuronal elements that are indicative of dopaminergic neurotransmission in cerebellum suggest that this brain region may contribute to the motor symptoms or dyskinesia seen in Parkinson's disease. Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of markers for dopaminergic neurotransmission in the cerebellum from postmortem brain tissue obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. Dopamine D1-3 receptors, tyrosine hydroxylase and dopamine transporter mRNA was detected in the uvula and nodulus (lobules 9 and 10, respectively) of the vermis of cerebellum from normal individuals. In Parkinson's disease, the level of dopamine D1 and D3 receptor mRNA was significantly reduced in lobule 9 and the level of tyrosine hydroxylase mRNA was significantly reduced in lobule 10. No alteration in the level of dopamine D2 receptor or dopamine transporter mRNA was found in either lobule in patients with Parkinson's disease. These results show that mRNA expression for the functional components of dopaminergic neurotransmission is present in human cerebellum. The discrete changes in the levels of dopamine D1 and D3 receptors and tyrosine hydroxylase mRNA in cerebellum from l-DOPA treated Parkinson's disease patients suggests that this brain area has a role in the symptoms of Parkinson's disease and/or the beneficial/side-effects of treatment.</p
Dopamine D<sub>1</sub> receptor expression in human basal ganglia and changes in Parkinson's disease
No full textThe expression of the human dopamine D1 receptor was examined by reverse transcription polymerase chain reaction (RT-PCR) and radioligand binding using [3H]-SCH23390 in post-mortem brain tissue that was obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. D1 receptor mRNA and specific [3H]-SCH23390 binding sites were found in both striatal (nucleus accumbens, caudate nucleus and putamen) and extrastriatal (globus pallidus and substantia nigra) brain regions. In parkinsonian brain, D1 receptor mRNA was increased in the nucleus accumbens, while a decrease was detected in the substantia nigra pars compacta. No change in D1 mRNA levels was found in the other brain areas examined. An increase in the density of specific [3H]-SCH23390 binding sites was found in the anterior putamen and a decrease in the external segment of the globus pallidus, no changes were detected elsewhere. This study demonstrates that regulation of D1 receptor expression in the brain of patients dying with Parkinson's disease that were treated with L-DOPA is confined to small alterations in restricted brain regions.</p
Noribogaine: An active metabolite of the indole alkaloid ibogaine as an anti-addiction pharmacotherapy
No full textThe consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burden on an already over-burdened health care system. A non-addicting pharmacological agent in combination with psychotherapy may prove a viable alternative to interdiction of supply and incarceration. Anecdotal reports from addict self-help groups suggest that ibogaine may block opiate withdrawal and reduce drug craving for cocaine and heroin for extended time periods. While ibogaine has diverse CNS effects, the pharmacological targets underlying the physiological and psychological actions of ibogaine are not completely understood. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. The purpose of this dissertation was to determine the metabolic disposition of ibogaine, investigate the basis of gender differences in pharmacokinetics, and to determine the mechanism of action of the long-acting metabolite.The results of this dissertation demonstrate that: (1) ibogaine is O-demethylated to noribogaine predominantly by the isozyme CYP2D6; (2) gender differences in behavioral studies following ibogaine administration may be due to the sex hormone-dependent biotransformation of ibogaine to noribogaine; (3) noribogaine acts as a full agonist at the mu opioid receptor likely leading to an alleviation of the symptoms of withdrawal; and (4) preliminary assays using tritiated noribogaine demonstrate multiphasic affinities displaying constants that are in agreement with inhibitory constants from previous studies demonstrating affinities for the 5HT transporter and mu opioid receptor. Taken together, the results of this dissertation indicate that given the long-term presence of noribogaine along with its capacity to reset multiple opioid receptors and block reuptake at the 5HT transporter may explain how only a single dose of ibogaine in humans is able to block withdrawal symptoms and to interrupt psychostimulant and opiate dependence in humans.</p
Recommended from our members
Noribogaine: An active metabolite of the indole alkaloid ibogaine as an anti-addiction pharmacotherapy
No full textThe consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burden on an already over-burdened health care system. A non-addicting pharmacological agent in combination with psychotherapy may prove a viable alternative to interdiction of supply and incarceration. Anecdotal reports from addict self-help groups suggest that ibogaine may block opiate withdrawal and reduce drug craving for cocaine and heroin for extended time periods. While ibogaine has diverse CNS effects, the pharmacological targets underlying the physiological and psychological actions of ibogaine are not completely understood. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. The purpose of this dissertation was to determine the metabolic disposition of ibogaine, investigate the basis of gender differences in pharmacokinetics, and to determine the mechanism of action of the long-acting metabolite.The results of this dissertation demonstrate that: (1) ibogaine is O-demethylated to noribogaine predominantly by the isozyme CYP2D6; (2) gender differences in behavioral studies following ibogaine administration may be due to the sex hormone-dependent biotransformation of ibogaine to noribogaine; (3) noribogaine acts as a full agonist at the mu opioid receptor likely leading to an alleviation of the symptoms of withdrawal; and (4) preliminary assays using tritiated noribogaine demonstrate multiphasic affinities displaying constants that are in agreement with inhibitory constants from previous studies demonstrating affinities for the 5HT transporter and mu opioid receptor. Taken together, the results of this dissertation indicate that given the long-term presence of noribogaine along with its capacity to reset multiple opioid receptors and block reuptake at the 5HT transporter may explain how only a single dose of ibogaine in humans is able to block withdrawal symptoms and to interrupt psychostimulant and opiate dependence in humans.</p
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
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
- …
