1,720,963 research outputs found
Varenicline decreases nicotine but not alcohol self-administration in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats
Full text linkBackground: Alcohol and nicotine are largely co-abused. Here, we investigated whether concurrent exposure to both addictive drugs influences each other's consumption and whether varenicline attenuates alcohol consumption in the presence of nicotine. Methods: Marchigian Sardinian alcohol-preferring (msP) rats trained to simultaneously self-administer oral alcohol (10% v/v) and intravenous nicotine (30. μg/kg/inf) were used. Additional groups of rats were trained to self-administer either alcohol or nicotine. Further, msP rats were also trained to self-administer nicotine followed by 22-h/day access to alcohol and water in a two bottle free choice paradigm or water alone. The effects of varenicline (0.0, 0.3, 1.0, 3.0. mg/kg, p.o.) on alcohol and nicotine consumption were tested. Results: In a self-administration paradigm, msP rats showed a significantly high level of alcohol and nicotine intake when the drugs were administered alone. However, when access to both drugs occurred concomitantly, the number of nicotine infusions self-administered was significantly decreased. Nicotine self-administration was markedly reduced by varenicline regardless of whether it was self-administered alone or concurrently with alcohol. In a two bottle choice test, varenicline significantly decreased nicotine self-administration but had no influence on alcohol consumption. Conclusion: Varenicline is highly efficacious in decreasing nicotine self-administration either alone or in combination with alcohol. However, varenicline failed to influence both operant responding for alcohol and home-cage alcohol drinking in msP animals. Taken together, our findings suggest that the effects of varenicline could be specific to nicotine under conditions where excessive alcohol drinking is facilitated by genetic factors as in msP rats
Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents
No full textRationale: Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. Objectives: To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. Methods: We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Results: Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. Conclusions: These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals
Biomarkers Mapping in a Neuropathic Pain Mice Model with Sciatic Nerve Chronic Constriction Injury (CCI).
No full textIntroduction
Neuropathic pain (NP) is an continuous pain caused by injury to the somatosensory system, is persistent and is refractory to analgesics. Common causes of NP include post herpetic neuralgia, diabetic neuropathy, cutting or compression of nerve. In this work a surgical mice model with a sciatic nerve chronic constriction injury (CCI) was used as a NP model. This CCI model involves both inflammatory and neuropathic components (1). The aim of this work was to identify significantly altered proteins in the blood of CCI operated mice in order to find possible predictive biomarkers of NP.
Methodology
To perform the CCI, the right sciatic nerve of the mice was exposed at the level of the mid-thigh. In CCI operated mice, three ligatures were loosely tied around the nerve, whereas in sham-operated controls, the sciatic nerve was exposed but not ligated. One week after surgery, the blood from the two groups was collected and the protein expression patterns was analyzed by a two-dimensional gel electrophoresis (2DE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to sequence protein signals.
Results
Results showed seven differentially expressed protein spots: five isoforms of haptoglobin, expressed only in the CCI operated mice group, transthyretin and apolipoprotein A-IV expressed mainly in the control group (sham-operated mice). Haptoglobin is an acute phase protein strongly associated with inflammation and is overexpressed during neuron damage. The five isoforms of haptoglobin observed in CCI operated mice serum are likely due to post-translational modifications.
Conclusions
This preliminary study provided data for potential biomarkers of neuropathic pain that can result useful for future neuropathic pain drug development
Biomarkers mapping of neuropathic pain in a nerve chronic constriction injury mice model
No full textNeuropathic pain is caused by a lesion or disease of the somatosensory nervous system and has a considerable impact on the quality of life. Neuropathic pain has a dynamic and complex aetiology and gives heterogeneous symptoms across patients; therefore, it represents an important clinical challenge. Current pharmacological treatment includes tricyclic antidepressant serotonin-noradrenaline uptake inhibitors such as duloxetine, pregabalin, and gabapentin. However, these drugs do not show efficacy in all patients suffering from neuropathic pain. In this work we used a nerve chronic constriction injury mice model based on the ligation of sciatic nerve to analyse, by two-dimensional electrophoresis and mass spectrometry, blood proteins significantly altered by neuropathic pain one-week after surgery. A sham-ligated group of mice acting as control and a group of ligated mice treated with gabapentin were also analysed. The results indicated that four haptoglobin isoforms were significantly more expressed, while transthyretin and alpha-2-macroglobulin expression decreased in the serum of the murine neuropathic pain model with respect to the control mice. Interestingly, the treatment with the gabapentin reversed these conditions. The outcomes of this study can provide a further understanding of the pathophysiological meaning of the biomarkers involved in neuropathic pain
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
Analgesic tolerance to morphine is regulated by PPARγ
Full text linkOpioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice
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
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