115,293 research outputs found
Erratum to: Proximal humeral fractures in elderly patients (Aging Clinical and Experimental Research, (2013), 25, S1, (85-87), 10.1007/s40520-013-0078-x)
No full textIn the original publication of the article, the name of the third author was incorrectly published as C. Capra. However, the correct name should read as P. Capra
Molecular and functional aspects of human cysteinyl leukotriene receptors
No full textThe cysteinyl leukotrienes (cys-LTs), i.e. LTC(4), LTD(4) and LTE(4), trigger contractile and inflammatory processes through the specific interaction with cell surface receptors belonging to the purine receptor cluster of the rhodopsin family of the G protein-coupled receptor (GPCR) genes. Cys-LTs have a clear role in pathophysiological conditions such as asthma, allergic rhinitis and other nasal allergies, and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Pharmacological studies have identified two classes of cys-LT receptors (CysLT(1) and CysLT(2)) based on their sensitivity to CysLT(1) selective antagonists, albeit there is evidence for additional subtypes. Molecular cloning of the human CysLT(1) and CysLT(2) receptors has confirmed both their structure as putative seven transmembrane domain G protein-coupled receptors and most of the previous pharmacological characterization. The rank order of potency of agonist activation for the CysLT(1) receptor is LTD4 > LTC4 > LTE4 and for the CysLT(2) receptor is LTC4 = LTD4 > LTE4. The CysLT(1) receptor is most highly expressed in spleen, peripheral blood leukocytes, interstitial lung macrophages and in airway smooth muscle. The CysLT(2) receptor is mostly expressed in heart, adrenals, placenta, spleen, peripheral blood leukocytes and less strongly in the brain. Gene cloning of CysLT(1) and CysLT(2) receptors has renewed the attention on the cys-LTs field and will, hopefully, encourage future studies on the regulation of CysLT receptors expression and the dissection of their signalling pathways. Furthermore, the peculiar pattern of expression of the two receptor subtypes will promote the discovery of new functions for cys-LTs in physiological and pathological conditions. Only CysLT(1) selective receptor antagonists have been described to date and are currently available for the treatment of asthma. Molecular cloning of different CysLT receptor subtypes will certainly foster the development of new selective antagonists based on molecular modelling studies
Leukotriene modifiers in asthma management
No full textThe prevalence of asthma is increasing, especially among children. Despite the attention focused on the acute phase of asthma, asthmatic airways demonstrate increased inflammatory cell infiltration and irreversible structural alterations (remodeling). Thus, therapy must transcend the control of symptoms and focus on the prevention of chronic inflammation, which progressively evolves toward airway remodeling. Leukotrienes have been demonstrated to play a causative role both in the early bronchoconstriction noted in asthmatics and in the late chronic inflammatory component, and drugs that can inhibit the actions or synthesis of leukotrienes (leukotriene modifiers) are now available by prescription
Quattro note alla Pitica nona di Pindaro (vv. 5-25; 87-92)
No full textExegetical notes on 13 (Pindar conjures up the beginning of the Hesiodic Catalogue), 5-25 (Pindar turns the Catalogue's linear story into a complex 'récit'), 23-25 (Hypnos is personified and as such is 'murdered' (analisko) by Cyrene) and 87-92 (on the metapoetic meaning of Dirce's waters)
Rosuvastatin inhibits human airway smooth muscle cells mitogenic response to eicosanoid contractile agents
No full textBACKGROUND: The concept of permanent narrowing of the airways resulting from chronic inflammation and fibrosis is called remodeling and is a common feature of asthma and chronic obstructive pulmonary disease (COPD). The eicosanoid contractile agents thromboxane A2 (TxA2) and cysteinyl-leukotriene D4 (LTD4) are among the recognized mitogens for human airway smooth muscle (ASM) cells. Statins are known to possess anti-inflammatory and immunomodulatory properties that are independent on their cholesterol-lowering effects and may result in clinical lung benefits. Rosuvastatin is the last agent of the lipid-lowering drugs to be introduced and experimental evidence indicates that it possess favorable pleiotropic effects in the cardiovascular and nervous systems. Yet, no data is available in the literature regarding its effects on human airway remodeling. The present study was aimed at examining the effect of rosuvastatin and the involvement of prenylated proteins in the response of human ASM cells to serum, epidermal growth factor (EGF) and eicosanoid contractile mitogens that activate TxA2 prostanoid and LTD4 receptors.
METHODS: Cell growth was assessed by nuclear incorporation of [(3)H]thymidine in human ASM cells serum-starved and then stimulated for 48 h in MEM plus 0.1% BSA containing mitogens in the absence and presence of modulators of the mevalonate and prenylation pathways.
RESULTS: We found that rosuvastatin dose-dependently inhibited serum-, EGF-, the TxA2 stable analog U46619-, and LTD4-induced human ASM cells growth. All these effects were prevented by pretreatment with mevalonate. Addition of the prenylation substrates farnesol and geranylgeraniol reversed the effect of rosuvastatin on EGF and U46619, respectively. Interestingly, only mevalonate showed restoration of cell growth following rosuvastatin treatment in LTD4 and LTD4 plus EGF treated cells, suggesting a possible involvement of both farnesylated and geranylgeranylated proteins in the cysteinyl-LT-induced cell growth.
CONCLUSIONS: The hydrophilic statin rosuvastatin exerts direct effects on human ASM cells mitogenic response in vitro by inhibiting prenylation of signaling proteins, likely small G proteins. These findings are consistent with previous observed involvement of small GTPase signaling in EGF- and U46619-induced human airway proliferation and corroborate the recent interest in the potential clinical benefits of statins in asthma/COPD
Leukotriene receptor antagonists in the treatment of allergic rhinitis
No full textLeukotriene receptor antagonists (LTRAs) have been long used in the therapy of some forms of asthma. Indeed, cysteinyl-leukotrienes (cysteinyl-LTs), potent lipid mediators derived from the oxidative metabolism of the arachidonic acid, are synthesized in response to different immune and inflammatory stimuli, and are deeply involved in the pathophysiology of asthma. A number of molecular and clinical studies substantiate a role for cysteinyl-LTs and their receptors also in allergic rhinitis,
indicating that they contribute to nasal allergy increasing
blood flow and nasal airway resistance, nasal mucous secretion and congestion. Considering that cysteynil-LTs play a critical role in the pathogenesis of both these diseases, a common therapeutic approach would seem logical. The LTRA therapeutic potential in allergic rhinitis has been, therefore, evaluated in a number of clinical trials that have demonstrated their safety and efficacy. LTRAs, thus, can provide an effective treatment option for patients with allergic rhinitis, and are generally used as an adjunct in the treatment of a patient who does not have an adequate response to antihistamines, a nasal corticosteroid, or both. In addition, LTRAs are beneficial for large proportion of patients suffering also from asthma. However, despite encouraging results, their place in the therapy of allergic rhinitis is not completely defined, and, as today, topical nasal steroid still should be considered the first-line therapy. It is likely that future developments in the pharmacogenetic will allow a more effective use of these drugs as, at present it is largely recognized that different genetic phenotypes reflect different responses to LTRAs. Today, unfortunately, it is not yet possible to identify patients with an LT-“dependent” disease and to predict responders or non-responders other than by use of a trial of therap
Ancistrocerus capra subsp. spenceri Bequaert 1944
No full text<i>Ancistrocerus capra spenceri</i> Bequaert, 1944 <p> <i>Ancistrocerus antilope</i> var. (or subsp.) <i>spenceri</i> Bequaert, 1944: 277 (♀; type locality: “ British Columbia: Kamloops ” [Canada]; holotype, ♀ [Museum of Comparative Zoology, Harvard University, Cambridge, Massachusetts]).</p> <p>DISTRIBUTION: Canada (British Columbia).</p>Published as part of <i>Fateryga, Alexander V., Carpenter, James M. & Fateryga, Valentina V., 2023, Ancistrocerus capra (de Saussure, 1857), a Valid Species, Not a Synonym of A. antilope (Panzer, 1798) (Hymenoptera: Vespidae: Eumeninae), pp. 1-16 in American Museum Novitates 2023 (4002)</i> on page 7, DOI: 10.1206/4002.1, <a href="http://zenodo.org/record/10134000">http://zenodo.org/record/10134000</a>
A role for inflammatory mediators in heterologous desensitization of CysLT(1) receptor in human monocytes
No full textCysteinyl-leukotrienes (cysteinyl-LT) are rapidly generated at sites of inflammation and, in addition to their role in asthma, rhinitis, and other immune disorders, are increasingly regarded as significant inflammatory factors in cancer, gastrointestinal, cardiovascular diseases. We recently demonstrated that in monocyte/macrophage-like U937 cells, extracellular nucleotides heterologously desensitize CysLT(1) receptor (CysLT(1)R)-induced Ca2+ transients. Given that monocytes express a number of other inflammatory and chemoattractant receptors, this study was aimed at characterizing transregulation between these different stimuli. We demonstrate that in U937 cells and in primary human monocytes, a series of inflammatory mediators activating G(i)-coupled receptor (FPR1, BLT1) desensitize CysLT(1)R-induced Ca2+ response unidirectionally through activation of PKC. Conversely, PAF-R, exclusively coupled to G(q), cross-desensitizes CysLT(1)R without the apparent involvement of any kinase. Interestingly, G(s)-coupled receptors (beta(2)AR, H1/2R, EP2/4R) are also able to desensitize CysLT(1)R response through activation of PKA. Heterologous desensitization seems to affect mostly the G(i)-mediated signaling of the CysLT(1)R. The hierarchy of desensitization among agonists may be important for leukocyte signal processing at the site of inflammation. Considering that monocytes/macrophages are likely to be the major source of cysteinyl-LT in many immunological and inflammatory processes, shedding light on how their receptors are regulated will certainly help to better understand the role of these cells in orchestrating this complex network of integrated signals.-Capra, V., M. R. Accomazzo, F. Gardoni, S. Barbieri, and G. E. Rovati. A role for inflammatory mediators in heterologous desensitization of CysLT1 receptor in human monocytes
Cysteinyl-Leukotriene Receptors and Cellular Signals
No full textCysteinyl-leukotrienes (cysteinyl-LTs) exert a range of proinflammatory effects, such as constriction of airways and vascular smooth muscle, increase of endothelial cell permeability leading to plasma exudation and edema, and enhanced mucus secretion. They have proved to be important mediators in asthma, allergic rhinitis, and other inflammatory conditions, including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. The classification into subtypes of the cysteinyl-LT receptors (CysLTRs) was based initially on binding and functional data, obtained using the natural agonists and a wide range of antagonists. CysLTRs have proved remarkably resistant to cloning. However, in 1999 and 2000, the CysLT1R and CysLT2R were successfully cloned and both shown to be members of the G-protein coupled receptors (GPCRs) superfamily. Molecular cloning has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Recombinant CysLTRs couple to the Gq/11 pathway that modulates inositol phospholipids hydrolysis and calcium mobilization, whereas in native systems, they often activate a pertussis toxin-insensitive Gi/o-protein, or are coupled promiscuously to both G-proteins. Interestingly, recent data provide evidence for the existence of an additional receptor subtype that seems to respond to both cysteinyl-LTs and uracil nucleosides, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Finally, a cross-talk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize recent data derived from studies on the molecular and cellular pharmacology of CysLTRs
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