1,721,169 research outputs found
I farmaci antimuscarinici non selettivi : considerazioni sul loro impiego nella broncopneumopatia cronica ostruttiva (BPCO)
No full textA number of data from animal models and humans supports the theory that alteration of parasympathetic neuronal control of respiratory smooth muscle may increase bronchoconstriction in response to vagal stimulation, leading to airway hyperresponsiveness. Even if the mechanism/s of this phenomenon, particularly evident in chronic obstructive pulmonary disease (COPD), is unknown, impairment of pulmonary parasympathetic control may play an important role. Nowadays the treatment of this condition with anticholinergic drugs has reached a great success. On this ground, the future for inhaled anticholinergic drugs for the treatment of COPD appears to remain in their combination with β2-agonists and phosphodiesterase-4 inhibitors. Non selective antimuscarinic compounds could be a good choice, since M2 muscarinic receptors on airway smooth muscle inhibit the formation of cyclic adenosine monophosphate. Moreover, a sufficient blockade of M3 muscarinic receptors would antagonize the increase of acetylcholine release due to the inhibition of neuronal M2 muscarin
Inattivazione dell’istone-deacetilasi : chiave di volta nella resistenza agli steroidi in pazienti COPD
No full textLe malattie infiammatorie polmonari sono caratterizzate da un’aumentata espressione di numerosi geni infiammatori che sono regolati da vari fattori di trascrizione come il fattore nucleare-kB e AP-1. L’espressione di tali geni è a sua volta dipendente dall’acetilazione degli istoni (core histones) mediante molecole coattivatrici dotate di attività acetiltransferasi intrinseca. Diversamente, la repressione dei geni infiammatori è mediata dalla deacetilazione degli istoni iperacetilati, e da altri elementi di corepressione. I pazienti affetti da broncopneumopatia cronica ostruttiva (COPD), ma non quelli affetti da asma, sono poco sensibili agli steroidi, come d’altra parte si evince dallo scarso beneficio clinico. Gli steroidi debbono la loro attività antinfiammatoria al reclutamento dell’istone deacetilasi-2 (HDAC2) ai geni trascriventi, spegnendo così la trascrizione di geni infiammatori. In pazienti con broncopneumopatia cronica ostruttiva (COPD),
la funzione HDAC2 appare alterata nei fumatori di sigarette ed è ridotta dallo stress ossidativo, un evento che ben si correla a una marcata inibizione della risposta agli steroidi. La conoscenza dei meccanismi molecolari che sono alla base dell’espressione e della repressione di geni infiammatori suggerisce nuovi approcci farmacologici in grado di sbloccare la resistenza agli steroidi al fine di ripristinare un importante trattamento antinfiammatorio non solo nella COPD, ma anche in altre forme infiammatorie ad andamento cronico non polmonari
Pathophysiology of coronary vasomotor tone
No full textThe Authors focus the great importance of the endothelium-dependent relaxation in normal and diseased human coronary arteries. The impairment or loss of this powerful dilator process, that is multifactorial and related to the stage of development of the endothelial damage seems to be, beyond all doubt, implicated with vasospasm and thrombosis. Furthermore the response of coronary smooth muscles to vasoconstrictors, particularly to serotonin, may be augmented. These vasoconstrictors may be present in larger amount at the site of the rupture of atheromatous plaque, following platelet deposition and aggregation that trigger the release of platelet-derived products such as ADP, 5-HT and eicosanoids. The recognition and the increasing knowledge on the relationship between endothelial-relaxing mechanism dysfunction and coronary heart disease is certainly leading to new hope for a more rational therapeutical intervention
Il recettore H4 dell’istamina: possibile target di nuovi farmaci per il trattamento delle allergie croniche
No full textThe selective recruitment and activation of eosinophils and mastocytes into the tissue from peripheral blood, represents a crucial pathogenetic moment which predisposes the chronic trend of allergic diseases. The results reported in this original article are the direct prove that chemotaxis of both eosinophils and mastocytes may be mediated also by histamine via activation of specific histamine H4 receptor subtype which is expressed on the surface of these proinflammatory cells. Therefore, this histamine H4 receptor subtype is considered a new pharmacological target leading to development of potent highly selective antagonists with considerably therapeutical potential in allergic disease
Comparative anti-inflammatory effects of roxithromycin, azithromycin and clarithromycin
No full textThere are many published reports on the anti-inflammatory effects of macrolides, some dating back to the introduction of erythromycin. Macrolides have been shown to affect a number of the processes involved in inflammation, including the migration of neutrophils, the oxidative burst in phagocytes and the production of various cytokines, although the precise mechanisms are not clear. These effects have been linked to the ability of macrolides to accumulate in mammalian cells. Roxithromycin, a macrolide with better plasma concentrations and higher tissue concentrations than erythromycin, has been tested in a standard animal model used for evaluating anti-inflammatory drugs. When rats were given a prophylactic dose (20 mg/kg), roxithromycin suppressed the oedema produced by injecting carrageenin into the paw with effects almost equal to that seen with the non-steroidal anti-inflammatory drug nimesulide. Azithromycin and clarithromycin, macrolides with better pharmacokinetics than erythromycin, only showed slight anti-inflammatory effects. These results confirm that roxithromycin has anti-inflammatory properties in vivo and encourage the investigation of its mode of action
"La Sapienza" a Mozia. Quarant'anni di ricerca archeologica (1964-2004)
No full textSaggio sugli scavi a MoziaEssay on the excavations at Mothy
Alpha-lipoic acid and docosahexaenoic acid: a positive interaction on the carrageenan inflammatory response in rats
No full textPeripheral nerves are subject to the same types of problems as other tissues: inflammation, toxicity, swelling, permeability, leading to neuropathies. Nutrients offer an alternative for people who want to avoid the side effects
of prescription drugs.
These studies were designed to assess the pharmacodynamic interaction between alpha-lipoic acid (ALA) and docosahexaenoic acid (DHA) in controlling the inflammatory
response induced by carrageenan in the rat. Particularly, the activity of ALA (100 mg/kg per os) and DHA (200 mg/kg per os), given alone or in combination, was evaluated by paw oedema method.
The results of the present study clearly indicate that the new formulation containing ALA plus DHA, in a range of 2:1, had significantly greater effect than either DHA
or ALA alone in antagonizing carrageenan-induced inflammatory response.
These results indicate that ALA plus DHA induce a favourable pharmacodynamic interaction which can be considered to be synergistic, at least in these experimental
setting
An amino acids mixture improves the hepatotoxicity induced by acetaminophen in mice
Full text linkAcetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 : 1 : 1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2 mmol/kg) or high dose (8 mmol/kg) of APAP. DDM-GSH (0.4 to 1.6 mmol/kg) was given ip to mice 1 h before the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury
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