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Radiological analysis of gastrointestinal dysmotility in a model of central nervous dopaminergic degeneration: Comparative study with conventional in vivo techniques in the rat
No full textIntroduction: Gastrointestinal (GI) motility disorders includemany clinical manifestations associatedwith various
pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to identify the functional abnormality and to unravel the underlying mechanisms, in order to design adequate therapeutic interventions.
Methods: In the present study, we applied radiological analysis, a common tool in clinical practice, to follow up
in vivo the progression of GI dysmotility over time and along the entire GI tract in an animal model of central nervous dopaminergic degeneration and compared these results to those obtained with standard techniques commonly used to assess GI motor functions in small rodents. Results: Our radiological data, showing delayed gastricemptying and constipation, agree with and expand previous information obtained with other functional assays in the samemodel, suggesting that radiological analysis can be an appropriate method to explore GI dysmotility in animal models of human pathologies. Discussion: In this studywe have applied for the first time the GI radiological analysis to an animal model of central nervous dopaminergic degeneration providing a non-invasive/animal-preserving approach, ethicallymore acceptable and useful to follow up the development of GI dysmotility in pathologies evolving over time
Gastrointestinal symptoms and local oxidative stress in a model of Parkinson's Disease in rats
No full textCaratterizzazione in vivo e in vitro della dismotilità gastrointestinale nel modello di morbo di Parkinson indotto da 6-OHDA nel ratto
No full textThe aetiology of Parkinson's disease (PD), an aging-related disease characterized by progressive degeneration of dopaminergic neurons of the substantia nigra is not fully clarified yet, and moreover, there is an ever-increasing understanding that this disease is more than a motor disorder. Research into the non motor symptoms of PD is the focus of intense investigations, and there is hope of developing treatments that not only arrest the progress of the disease but stop it in its tracks. Among the non motor autonomic disorders, complications in the gastrointestinal (GI) system are the most peculiar, which degrade the quality of life of the patient and may interfere, as in the case of changes in the normal gastrointestinal transit, with the proper absorption of drugs used in the treatment of the disease itself. Moreover they can appear in very early stage of the disease, or even before the onset of motor symptoms, until they have been mentioned as possible pre-clinical signs.
The purpose of the present thesis work was to characterize and study the effects of a central dopaminergic parkinsonian deficit, reproduced in Sprague Dawley rats bearing nigrostriatal 6-hydroxydopamine (6-OHDA) lesion, on the motor functions of the gastrointestinal tract. It has been adopted different in vivo methods to evaluate macroscopically the gastric motility and intestinal transit, and subsequently in vitro studies to verify the presence of any neuronal or receptor changes or any disruption caused by oxidative stress, and also to check the functionality of the pacemaker cells, Interstitial Cells of Cajal (ICC). In addition, it has been evaluated the evolution of gastrointestinal disorders following an oral subchronic four weeks treatment with L-DOPA/Benserazide, still considered a "gold standard" in the treatment of Parkinson's disease.
The in vivo results showed alterations of the gastrointestinal motility which develop in different time points following the whole course of the experiments. It has been demonstrated the presence of a delayed emptying of the stomach and a slowed intestinal transit after 8 weeks from 6-OHDA intracerebral injection, which can reflect the symptoms of gastroparesis and constipation detected in PD patients. The in vitro investigation provides evidence that 6-OHDA rats present a loss of responsiveness to exogenous contractile agents in gastric circular muscles and an impairment of pyloric
nitrergic control. To test the validity of the hypothesis regarding the role and involvement of ICC in gastroparesis, never investigated before in the experimental model adopted here, it has been performed an immunohistochemical study detecting a disruption of ICC plasticity consequently to the dopaminergic central deficit in the gastric regions of fundus, corpus and antrum.
As regards the oral subchronic treatment with L-DOPA/Benserazide, it shows a partial benefit after 8 weeks in terms of gastric and colonic dysmotility, bringing it to normal values. While it decreases the state of oxidative stress, detected by the index of lipoperoxidation MDA, in stomach and terminal colon.
In conclusion, this research has provided significant results and methodological knowledge. Comparing different types of investigations, it has been possible to identify the modalities that, in this specific experimental model endowed with translational validity, with higher reproducibility and limited variability, allow to monitor in vivo the gastrointestinal motor activity
Radiological Analisys of Gastrointestinal Dysmotility Associated with Central Dopaminergic Impairement in an Animal Model Parkinson's Disease (PD)
No full textEnteric dysfunctions in experimental Parkinson's disease: alterations of excitatory cholinergic neurotransmission regulating colonic motility in rats
Get PDFParkinson's disease (PD) is frequently associated with gastrointestinal symptoms, mostly represented by constipation and defecatory dysfunctions. This study examined the impact of central dopaminergic denervation, induced by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, on distal colonic excitatory cholinergic neuromotor activity in rats. Animals were euthanized 4 and 8 weeks after 6-OHDA injection. In vivo colonic transit was evaluated by radiological assay. Electrically and carbachol-induced cholinergic contractions were recorded in vitro from longitudinal and circular muscle colonic preparations, while acetylcholine levels were assayed in their incubation media. Choline acetyltransferase (ChAT), HuC/D (pan-neuronal marker), muscarinic M2 and M3 receptors. As compared with control rats, at week 4 6-OHDA-treated animals displayed the following changes: decreased in vivo colonic transit rate; impaired electrically evoked neurogenic cholinergic contractions; enhanced carbachol-induced contractions; decreased basal and electrically stimulated acetylcholine release from colonic tissues; decreased ChAT immunopositivity in the neuromuscular layer; unchanged density of HuC/D immunoreactive myenteric neurons; increased expression of colonic muscarinic M2 and M3 receptors. The majority of such alterations were detected also at week 8 post-6-OHDA injection. These findings indicate that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory neurotransmission characterized by a loss of myenteric neuronal ChAT positivity and decrease in acetylcholine release, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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