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Un agonista PPAR alfa protegge il sistema NANC inibitorio della trachea di cavia dall’effetto dell’inalazione di persolfato d’ammonio [A PPAR alpha agonist protects the NANC inhibitory system of the guinea pig trachea from the effect of inhaled ammonium persulphate]
No full textL'inalazione di persolfato d'ammonio, nell'ambito di un globale effetto flogogeno sulle vie aeree, nel quale possono avere parte meccanismi immunomediati umorali e cellulari e meccanismi di danno diretto di tipo irritativo, ha mostrato di ridurre il rilasciamento NANC (non adrenergico, non colinergico) inibitorio (NANCi) della trache di cavia. La stimolazione dei PPAR (Peroxisome Proliferator-Activated Receptors) appartenenti al tipo gamma ha mostrato di avere alcuni effetti antinfiammatori nelle vie aeree, mentre non sono conosciuti effetti analoghi mediati dalla stimolazione dei PPAR-alfa, sebbene anche la stimolazione di questi ultimi abbia mostrato di esercitare effetti antinfiammatori in altri tessuti. In questo studio la somministrazione in vivo dell'agonista per i PPAR-alfa WY 14643 ha prevenuto la riduzione del rilasciamento NANC indotta dall'inalazione di persolfato d'ammonio nella trachea di cavia. Queste osservazioni suggeriscono che i PPAR-alfa siano un bersaglio farmacologico potenzialmente sfruttabile nell'ambito della terapia antiasmatica e, in particolare, che la loro stimolazione con opportuni agonisti possa contribuire a stabilizzare il tono delle vie aeree, preservando la funzione del principale sistema broncodilatatore intrinseco
Cord blood-derived endothelial progenitor cells: a superior building company in the angiogenesis market: P599
No full textA PPAR-α agonist protects the non-adrenergic, non-cholinergic inhibitory system of guinea pig trachea from the effect of inhaled ammonium persulphate. a pilot study
Get PDFPurpose/Aim of the study. Inhaled ammonium persulphate (AP) reduces non adrenergic, non cholinergic (NANC) relaxation in the guinea pig trachea, as a part of its inflammatory effects. Peroxisome Proliferator-Activated Receptor (PPAR) stimulation has shown anti-inflammatory properties. This study aimed at evaluating whether the PPAR-α agonist WY 14643 can prevent the reduction in NANC relaxation caused by inhaled AP in the guinea pig trachea.
Materials and Methods. Four groups of ten male guinea pigs were treated for three weeks with inhaled AP (10 mg/m3, 30 min per day, group A), saline (group B), AP and WY 14643 (0.36 μM/die, per os, group C), and AP, WY 14643 and the PPAR-α antagonist GW 6471 (0.36 μM/die, per os, group D). NANC relaxations to electrical field stimulation (EFS) at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes.
Results. The tracheal NANC relaxations were reduced by 90.3% in group A, as compared to group B. In group C, they were reduced by only 22.2%. In group D, they were reduced by 92.6 %. PPAR-α receptors were detected in inhibitory nerve fibers within the trachea as shown by immonohistochemical analysis.
Conclusions. The PPAR-α agonist WY 14643 protects the NANC inhibitory system of the guinea pig trachea from the effect of inhaled ammonium persulphate and its protective effect is antagonized by GW 6471. PPAR-α might be exploited as a pharmacological target in asthma therapy
Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.
Get PDFBackground: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. Objectives: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. Methods: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m(3) for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. Results: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 +/- 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 muM. Conversely, the response to the maximal concentration of carbachol (3 muM) was increased (p < 0.01). Conclusion: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma
Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea
No full textBackground: Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A1, A2a, A2b and A3. It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release. Objectives: We assessed the effect of A1 and A3 receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A1 and A3 receptors in tracheal inhibitory neurons. Methods: NANC responses at 3 Hz were evaluat- ed in the presence of 2-chloro-N6-cyclopentyladenosine (CCPA), a selective A1 agonist, and 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), a selective A3 agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 antagonist, or 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino[1,2,4]triazolo[1,5-c])quinazoline (MRS 1220), a selective A3 antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A1 or A3 adenosine receptors and processed by indirect immunofluorescence. Results: CCPA (10 nM-3 μM) inhibited NANC relaxations. DPCPX (10 nM) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1-100 nM). CCPA (10 nM-10 μM) contracted unstimulated tracheal preparations, an effect antagonized by 10 nM DPCPX, with a pKB value of 8.43. Cl-IB-MECA (10 nM-3 μM) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 nM). A1- and A3-positive neurons containing nNOS were detected in tracheal sections. Conclusions: Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A1 and A3 receptors
Intestinal dysmotility and enteric neurochemical changes in a Parkinson's disease rat model
No full textGastrointestinal disorders, constipation in particular, are the most common non-motor dysfunctions affecting Parkinson's disease (PD) patients. We have previously reported that rats bearing unilateral nigrostriatal lesion caused by 6-hydroxydopamine (6-OHDA) stereotaxic injection develop severe constipation together with a region-specific decrease of neuronal nitric oxide synthase (nNOS) in enteric neurons of the lower intestinal tract. Here, we extend these observations on other enteric neuronal subpopulations, investigating also the propulsive activity of isolated colonic specimens. Four weeks post 6-OHDA injection, lesioned rats showed a significant increase of vasoactive intestinal polypeptide (VIP) concomitant with the reduced expression of nNOS in the myenteric plexus of distal ileum and proximal colon; in particular VIP increased in a subpopulation of neurons actively expressing nNOS. On the other hand, choline acetyltransferase (ChAT) was not modified in any of the intestinal segments analyzed. Interestingly, we found a reduced expression of dopamine receptor type 2 (D2R) in proximal (-66.8%) and distal (-54.5%) colon, together with reduced peristalsis efficiency (decrease in intraluminal pressure and frequency of peristaltic events) in the 6-OHDA-lesioned rats. The selective depletion of dopaminergic nigrostriatal neurons is associated with changes in the expression of enteric inhibitory neurotransmitters, as well as of the D2R in intestinal specific regions. Moreover, 6-OHDA-lesioned rats demonstrated altered colon propulsive activity referable to the D2R decrease. Our findings unveil subtle mechanisms underlying the enteric neurochemical plasticity events evoked by disruption of the normal brain-gut cross-talk, giving a peculiar point of view on the pathophysiology of the severe constipation that frequently affects PD patients
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
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