1,721,018 research outputs found
Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a novel approach for reducing gastrointestinal toxicity.
No full textThe use of non-steroidal anti-inflammatory drugs (NSAID) for treatment of inflammatory conditions is significantly limited by the untoward effects of these compounds on the gastrointestinal tract. While the pathogenesis of 'NSAID-gastropathy' is not completely understood, there is good evidence that the process is directly linked to suppression of prostaglandin synthesis and possibly to neutrophil adherence to the vascular endothelium. Pretreatment of rats with a nitric oxide (NO) donor (sodium nitroprusside) was found to significantly reduce the extent of gastric injury induced by flurbiprofen. We therefore tested the effects of a novel derivative of flurbiprofen. This compound contains a moiety similar to the NO-releasing moieties found in many organic nitrates. This compound suppressed gastric prostaglandin synthesis as effectively as flurbiprofen, but caused significantly less haemorrhagic damage. The compound was also found not to induce small intestinal injury. Since the compound was found to exert anti-inflammatory effects comparable with flurbiprofen, NO-releasing NSAID may represent a novel class of drugs with markedly reduced gastrointestinal toxicity
Enhanced anti-inflammatory potency of a nitric oxide-releasing derivative of flunisolide: role of nuclear factor-kappaB.
No full textGastrointestinal safety and anti-inflammatory effects of a hydrogensulfide-releasing diclofenac derivative in the rat.
No full textBACKGROUND & AIMS: Gastrointestinal damage caused by nonsteroidal
anti-inflammatory drugs (NSAIDs) remains a significant clinical problem. Hydrogen
makes an important contribution to mucosal defense, and NSAIDs can suppress its
synthesis. In this study, we evaluated the gastrointestinal safety and
anti-inflammatory effects of a novel "HS-NSAID" (ATB-337) that consists of
diclofenac linked to a hydrogen sulfide-releasing moiety.
METHODS: The gastrointestinal injury-inducing effects of single or repeated
administration of diclofenac versus ATB-337 were compared in rats, as were their
effects on prostaglandin synthesis and cyclooxygenase-1 and -2 activities. The
ability of these drugs to reduce carrageenan-induced paw edema and to elicit
leukocyte adherence to the vascular endothelium (intravital microscopy) were also
examined in rats.
RESULTS: Diclofenac (10-50 micromol/kg) dose-dependently damaged the stomach,
while ATB-337 did not. Repeated administration of diclofenac caused extensive
small intestinal damage and reduced hematocrit by 50%. ATB-337 induced >90% less
intestinal damage and had no effect on hematocrit. Diclofenac, but not ATB-337,
elevated gastric granulocyte infiltration and expression of tumor necrosis factor
alpha, lymphocyte function-associated antigen 1, and intercellular adhesion
molecule 1. ATB-337 inhibited cycloxygenase-1 and cyclooxygenase-2 activity as
effectively as diclofenac. ATB-337 did not induce leukocyte adherence, whereas
diclofenac did, and was more potent at reducing paw edema.
CONCLUSIONS: An HS-NSAID spares the gastric mucosa of injury despite markedly
suppressing prostaglandin synthesis. This effect may be related to hydrogen
sulfide-mediated inhibition of tumor necrosis factor-alpha expression and of the
leukocyte adherence to vascular endothelium normally induced by cyclooxygenase
inhibitors
Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat
No full textBACKGROUND & AIMS: Gastrointestinal damage caused by nonsteroidal
anti-inflammatory drugs (NSAIDs) remains a significant clinical problem. Hydrogen
makes an important contribution to mucosal defense, and NSAIDs can suppress its
synthesis. In this study, we evaluated the gastrointestinal safety and
anti-inflammatory effects of a novel "HS-NSAID" (ATB-337) that consists of
diclofenac linked to a hydrogen sulfide-releasing moiety.
METHODS: The gastrointestinal injury-inducing effects of single or repeated
administration of diclofenac versus ATB-337 were compared in rats, as were their
effects on prostaglandin synthesis and cyclooxygenase-1 and -2 activities. The
ability of these drugs to reduce carrageenan-induced paw edema and to elicit
leukocyte adherence to the vascular endothelium (intravital microscopy) were also
examined in rats.
RESULTS: Diclofenac (10-50 micromol/kg) dose-dependently damaged the stomach,
while ATB-337 did not. Repeated administration of diclofenac caused extensive
small intestinal damage and reduced hematocrit by 50%. ATB-337 induced >90% less
intestinal damage and had no effect on hematocrit. Diclofenac, but not ATB-337,
elevated gastric granulocyte infiltration and expression of tumor necrosis factor
alpha, lymphocyte function-associated antigen 1, and intercellular adhesion
molecule 1. ATB-337 inhibited cycloxygenase-1 and cyclooxygenase-2 activity as
effectively as diclofenac. ATB-337 did not induce leukocyte adherence, whereas
diclofenac did, and was more potent at reducing paw edema.
CONCLUSIONS: An HS-NSAID spares the gastric mucosa of injury despite markedly
suppressing prostaglandin synthesis. This effect may be related to hydrogen
sulfide-mediated inhibition of tumor necrosis factor-alpha expression and of the
leukocyte adherence to vascular endothelium normally induced by cyclooxygenase
inhibitors
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
Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils.
No full textThe gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibitingN-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium
Platelets modulate gastric ulcer healing: role of endostatin and vascular endothelial growth factor release
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