1,721,097 research outputs found
Neutrophils, endothelial cells, and cysteinyl leukotrienes: a new approach to neutrophil-dependent inflammation?
No full textCysteinyl leukotrienes (cys-LT) have been historically involved with the pathogenesis of asthma, and cys-LT receptor antagonists and synthesis inhibitors are currently in use for the therapy of this disease. Nevertheless cys-LT possess very potent proinflammatory activities and may play a significant role in inflammatory processes other than asthma. Recent evidences obtained in our laboratory, as well as in others, show that unexpected, biologically significant amounts of cys-LT are formed upon cell-cell cooperation between neutrophils and endothelial cells, resulting from transfer of the synthesis intermediate leukotriene A4 from neutrophils to endothelial cells. Cys-LT formed upon neutrophil adhesion to endothelial cells may contribute to the alterations of microvasculature associated with the inflammatory response. In particular, nonsteroidal anti-inflammatory drug (NSAIDs)-induced neutrophil adhesion to gastric wall microvessels may contribute to the gastric damage associated to the use of NSAIDs. In agreement with this hypothesis, dual 5-LOX/COX inhibitors are characterized by reduced gastric damage when compared to nonspecific COX-inhibitors. Evidence provide support for the involvement of cys-LT in neutrophil-dependent inflammatory responses and suggest new potential application of 5-LO inhibition in anti-inflammatory pharmacological treatment
Eicosanoid transcellular biosynthesis : from cell-cell interactions to in vivo tissue responses
No full textThe biosynthesis of the biol. active metabolites of arachidonic acid involves a no. of enzymes that are differentially expressed in cells. Prostaglandins and thromboxanes are derived from the chem. unstable prostaglandin (PG) H2 intermediate synthesized by PGH synthases (cyclooxygenase-1/2) and leukotrienes from chem. unstable leukotriene A4 by 5-lipoxygenase. Addnl. enzymes transform these reactive intermediates to a variety of chem. structures known collectively as the lipid mediators. Although some cells have the complete cassette of enzymes required for the prodn. of biol. active prostaglandins and leukotrienes, the actual biosynthetic events often are a result of cell-cell interaction and a transfer of these chem. reactive intermediates, PGH2 and leukotriene A4, between cells. This process has come to be known as transcellular biosynthesis of eicosanoids and requires a donor cell to synthesize and release one component of the biosynthetic cascade and a second, accessory cell to take up that intermediate and process each into the final biol. active product. This review focuses on the evidence for transcellular biosynthetic events for prostaglandins, leukotrienes, and lipoxins occurring during cell-cell interactions. Evidence for arachidonic acid serving as a transcellular biosynthetic intermediate is presented. Expts. for transcellular events taking place in vivo that reveal the true complexity of eicosanoid biosynthesis within tissues are also reviewe
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
Le Basi Farmacologiche della terapia, edizione italinana di Goodman & Gilman The pharmacological bases of therapy X EDIZIONE
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Inhibition by lipoxygenase products of TXA2-like responses of platelets and vascular smooth muscle. 14-Hydroxy from 22:6n-3 is more potent than 12-HETE
No full textLipoxygenase products, which are formed in great amounts in platelets during their activation, have been prepared from arachidonic acid esterified in platelet phospholipids, and from two major PUFAs of fish fat, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. These compounds have been synthesized using platelet suspension as enzymic source, purified by high performance liquid chromatography, and their structure were checked by gas chromatography-mass spectrometry. Their effects were investigated in vitro upon human platelet aggregation induced by 11,9-epoxy-methano-analogue of PGH2 (U-46619) and upon thromboxane A2-induced vasoconstriction of rabbit aorta. All hydroxylated fatty acids inhibited U-46619-induced aggregation in a concentration-dependent fashion. Compounds issued from 22:6n-3 were the most potent inhibitors and their ic50 differed significantly from that of 12-hydroxy-eicosatetraenoic acid (12-HETE). Among them, 14-hydroxy-docosahexaenoic acid (14-OH-22:6) was the most effective anti-aggregating molecule (ic50: 0.45 μM 12-HETE and 14-OH-22:6 inhibited 60% and 75% of smooth muscle contraction induced by TXA2-like material, respectively. At 1 μM, solely 14-OH-22:6 had an inhibitory effect on andrenaline-, angiotensine- or histamine-induced contraction. Since thromboxane receptors in platelets and vascular smooth muscle cells present strong similarities, it is concluded that hydroxylated fatty acids can antagonize prostanoid action probably by interfering with their receptor sites
Transcellular synthesis of cysteinyl leukotrienes and neutrophil-dependent cerebral edema
No full textSimultaneous investigation of the neuronal and vascular compartments in the guinea pig brain isolated in vitro
No full textWe describe a new method for studying the interactions between vascular tone changes and neuronal activity in the arterially perfused isolated brain of the adult guinea pig maintained in vitro. Electrophysiological recordings were performed in the piriform and entorhinal cortices with the entire arterial bed preserved or after vascular restriction to the territories of median and posterior cerebral arteries of one hemisphere. The changes in vascular tone were measured by means of a pressure transducer. The arterial pressure was 53.77+/-12.74 mmHg in control conditions at 30 degreesC. Intraluminal application of vasoactive drugs, such as the tromboxane A2 receptor agonist U46619 (0.1 microM) and 5-HT (3 microM), induced an increase in the resistance to perfusion pressure that was prevented by the selective antagonists. The preservation of the endothelial function was verified by inducing the release of endogenous endothelial relaxant factor after intraluminal application of 1 microM acetylcholine. The study of the reciprocal interactions between neuronal activity and vascular tone modifications demonstrated that evoked responses in the piriform and entorhinal cortices were not modulated by rapid changes of the vascular tone. A sustained and elevated plateau of vasoconstriction maintained for several minutes determined a cortical spreading depression. Epileptiform discharges induced in limbic cortices by GABAa receptor blockade were consistently associated with a vasodilation (8.26+/-2.8 mmHg). The results demonstrate that the in vitro isolated guinea pig brain preparation can be exploited for studying simultaneously neuronal activity and cerebrovascular motility
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