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Intratracheal Administration (intratracheal + administration)
Selected AbstractsMast cells play a key role in the developmentof late airway hyperresponsiveness through TNF-,in a murine model of asthmaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2007Young-Suk Kim Abstract We have investigated the role of TNF-, in mast cell-mediated late airway hyperresponsiveness (AHR) using mast cell-deficient WBB6F1- W/Wv (W/Wv) mice in a murine model of asthma, which exhibits a biphasic increase in AHR. TNF-, levels in the airway and magnitude of late AHR in response to airway allergen challenge were severely impaired in W/Wv mice compared to their littermates. In addition to TNF-,, cytosolic phospholipase A2 (cPLA2) phosphorylation and enzymatic activity in the lungs were also impaired in W/Wv mice. Either anti-TNF-, antibody or an inhibitor of cPLA2 abolished late AHR in congeneic +/+ mice. Intratracheal administration of TNF-, resulted in increases in late AHR, cPLA2 phosphorylation, cPLA2 activity, and phosphorylation of mitogen-activated protein kinases. Mast cell replacement restored airway TNF-, level, cPLA2 phosphorylation and enzymatic activity in the lungs as well as late AHR in W/Wv mice. These data indicate that mast cells play a key role in the development of late AHR through liberation of TNF-,. [source] Intravenous and intratracheal administration of trimetoquinol, a fast-acting short-lived bronchodilator in horses with ,heaves'EQUINE VETERINARY JOURNAL, Issue 6 2006F. C. CAMARGO Summary Reason for performing study: Trimetoquinol (TMQ) is a potent ,-adrenoceptor agonist bronchodilator used in human medicine but has not been evaluated for potential use as a therapeutic agent for horses with ,heaves'. Objectives: To assess the pharmacodynamics of TMQ in horses with ,heaves' to determine potential therapeutic effects. Methods: Increasing doses of TMQ were administered to horses with ,heaves' by i.v. and intratracheal (i.t.) routes. Doses ranged 0.001,0.2 ,g/kg bwt i.v. and 0.01,2 ,g/kg bwt i.t. Cardiac and airways effects were assessed by measurement of heart rate (HR) and maximal change in pleural pressure (,Pplmax), respectively. Side effects of sweating, agitation and muscle trembling were scored subjectively. Duration of action to i.v. (0.2 ,g/kg bwt) and i.t. (2 ,g/kg bwt) TMQ was evaluated over 6 h. Results: Intravenous TMQ was an exceptionally potent cardiac stimulant. Heart rate increased at 0.01 ,g/kg bwt, and was still increasing after administration of highest dose, 0.2 ,g/kg bwt. Airway bronchodilation, measured as a decrease in ,Pplmax, also commenced at 0.01 ,g/kg bwt. By the i.t. route, TMQ was 50,100-fold less potent than by i.v. Side effects included sweating, agitation and muscle trembling. Overall, the onset of HR and bronchodilator effects was rapid, within about 3 min, but effects were over at 2 h. Conclusion: When administered i.v. and i.t., TMQ is a highly potent cardiac stimulant and a modest bronchodilator. It may not be an appropriate pharmacological agent by i.v. and i.t. routes for the alleviation of signs in horses with ,heaves'. Further studies of TMQ by oral and aerosol routes are necessary. Potential relevance: In horses, TMQ is a fast-acting bronchodilator with a short duration of action. It could be used as a rescue agent during an episode of ,heaves'. The i.v. and i.t. administration of TMQ is associated with side effects, similar to those reported for all other ,-agonists. However, other routes, such as aerosol and oral, may prove useful and safe for the alleviation of bronchoconstriction typical of ,heaves'. [source] Melatonin limits lung injury in bleomycin treated miceJOURNAL OF PINEAL RESEARCH, Issue 2 2005Tiziana Genovese Abstract:, Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. The aim of this study was to investigate the effect of melatonin on the lung injury caused by bleomycin (BLM) administration. Mice subjected to intratracheal administration of BLM developed significant lung injury characterized by a marked neutrophil infiltration [assessed by myeloperoxidase (MPO) activity] and by tissue edema. In addition, an increase of immunoreactivity to nitrotyrosine, poly-ADP-ribose (PAR) was also observed in the lung of BLM-treated mice. Also, lung injury induced by BLM administration was correlated with a significant loss of body weight and with a significant mortality. Administration of melatonin (10 mg/kg i.p.) daily significantly reduced the (i) loss of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation and (v) histological evidence of lung injury. Administration of melatonin also markedly reduced the nitrotyrosine and PAR formation. Taken together, our results demonstrate that treatment with melatonin significantly reduces lung injury induced by BLM in the mice. [source] Activation of the lung S1P1 receptor reduces allergen-induced plasma leakage in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009F-X Blé Background and purpose:, It has been suggested that intratracheal administration of the immunomodulator, FTY720, could have anti-inflammatory effects without causing a decrease in blood lymphocyte counts. However, the receptor responsible for this effect has not been defined. Experimental approach:, We have described, in a mouse model of allergen-induced inflammation, the use of proton magnetic resonance imaging to non-invasively assess lung fluid accumulation and inflammation. Here, we used this model to investigate the sphingosine-1-phosphate (S1P) receptor responsible for the anti-inflammatory effect of FTY720. Key results:, When given intranasally, FTY720 (3 and 10 µg·kg,1) inhibited by approximately 50% the allergen-induced accumulation of fluid in the lung detected by magnetic resonance imaging, but had no effect on the cellular inflammation in the airway space or on circulating blood lymphocytes. Inhibition of the infiltration of inflammatory cells into the airways was only observed at a dose of FTY720 that induced lymphopenia (100 µg·kg,1). Similar results were observed in S1P3 -deficient mice. The effect of FTY720 was mimicked by intranasal treatment of wild-type mice with a S1P1 -specific agonist, AUY954. Conclusions and implications:, Thus, in contrast to previously published work, our results suggest that systemic exposure of FTY720 is necessary to obtain an airway anti-inflammatory effect. On the contrary, inhibition of the allergen-induced accumulation of fluid in the lung, via activation of the S1P1 receptor, is obtainable without systemic effects. [source] Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse modelCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2004C. Sanbongi Summary Background Perilla and its constituent rosmarinic acid have been suggested to have anti-allergic activity. However, few studies have examined the effects on allergic asthma. Objective The purpose of this study was to evaluate the effect of oral administration of perilla leaf extract, which contains high amount of rosmarinic acid, on a murine model of allergic asthma induced by house dust mite allergen. Methods C3H/He mice were sensitized by intratracheal administration of Dermatophagoides farinae (Der f). Mice were orally treated with rosmarinic acid in perilla extract (PE) (1.5 mg/mouse/day). Results Der f challenge of sensitized mice elicited pulmonary eosinophilic inflammation, accompanied by an increase in lung expression of IL-4 and IL-5, and eotaxin. Daily treatment with rosmarinic acid in PE significantly prevented the increases in the numbers of eosinophils in bronchoalveolar lavage fluids and also in those around murine airways. Rosmarinic acid in PE treatment also inhibited the enhanced protein expression of IL-4 and IL-5, and eotaxin in the lungs of sensitized mice. Der f challenge also enhanced allergen-specific IgG1, which were also inhibited by rosmarinic acid in PE. Conclusion These results suggest that oral administration of perilla-derived rosmarinic acid is an effective intervention for allergic asthma, possibly through the amelioration of increases in cytokines, chemokines, and allergen-specific antibody. [source] | ||||||||||