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Marked Inhibitory Effect (marked + inhibitory_effect)
Selected AbstractsNitrergic,purinergic interactions in rat distal colon motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2004K. Van Crombruggen Abstract, Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5,-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic,purinergic pathways. Exogenous NO (10,6 to 10,4 mol L,1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+ -sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro- l -arginine methyl ester (l -NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10,3 mol L,1) but did not influence the amplitude. ODQ had no effect. TTX + l -NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP- , -S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5,4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l -NAME, ODQ or RB2. APA shortened the relaxations. l -NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l -NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3,,5,-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations. [source] Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering budsPHYTOTHERAPY RESEARCH, Issue 1 2005Domenico Trombetta Abstract The antiallergic properties of two lyophilized extracts obtained from Capparis spinosa L. flowering buds (capers) by methanol extraction, carried out at room temperature (CAP-C) or with heating at 60 °C (CAP-H), were investigated. The protective effects of CAP-H and CAP-C, orally administered (14.28 mg[sol ]kg), were evaluated against Oleaceae antigen challenge-induced and histamine-induced bronchospasm in anaesthetized guinea-pigs. Furthermore, the histamine skin prick test was performed on humans, applying a gel formulation containing 2% CAP-C (the only extract able to protect against histamine-induced bronchospasm) on the skin for 1 h before histamine application and monitoring the erythema by reflectance spectrophotometry. The CAP-H showed a good protective effect against the bronchospasm induced by antigen challenge in sensitized guinea-pigs; conversely, a significant decrease in the responsiveness to histamine was seen only in CAP-C pretreated animals. Finally, the CAP-C gel formulation possessed a marked inhibitory effect (46.07%) against histamine-induced skin erythema. These two caper extracts displayed marked antiallergic effectiveness; however, the protective effect of CAP-H was very likely due to an indirect mechanism (for example, inhibition of mediator release from mast cells or production of arachidonic acid metabolites); conversely, CAP-C is endowed with direct antihistaminic properties. The different mechanisms of action of CAP-H and CAP-C may be related to a difference in the extraction procedure and, thus, in their qualitative[sol ]quantitative chemical profile. Copyright © 2005 John Wiley & Sons, Ltd. [source] Comparative assessment of S. aureus microbial biofilm inhibition by an N-alkyl-polyethyleneimine covalently attached to PMMA or titanium in the Boston KeratoprosthesisACTA OPHTHALMOLOGICA, Issue 2009I BEHLAU Purpose Biofilms are matrix-associated microbial communities adherent to either biological surfaces or abiotic surfaces. They account for the majority of device-associated infections. Our goal herein is to minimize bacterial adherence and biofilm formation by comparative analysis of new polycations bound to bio-prosthetic ocular-associated materials, poly (methyl methacrylate) (PMMA) or titanium, using the Boston KPro as a model system. Methods Using S.aureus ocular-associated clinical isolates, a quantitative assessment of microbial biofilm formation by linear N,N-dodecyl,methyl-polyethyleneimine (DMPEI) (217 kDa) covalently bound to PMMA or titanium compared to the parent PMMA or Ti, respectively, has been performed using confocal laser scanning and electron microscopies. In addition, DMPEI-bound materials have been screened for corneal toxicity in both cell tissue culture and rodent models, and as compared to the original materials. Results A marked inhibitory effect in S. aureus biofilm formation on DMPEI-derivatized materials compared to the parent PMMA (3-4 fold) and Ti (2-fold), without conferring additional epithelial cell cytotoxicity in vitro, has been observed. Furthermore, we have found no additional tissue reactivity, and possibly even a protective effect, with DMPEI-derivatized materials in vivo. Conclusion We found that covalent derivatization with DMPEI of PMMA and Ti greatly reduces S. aureus biofilm formation in vitro compared to the parent materials. There was no additional cytotoxicity seen both in vitro and in vivo. Future studies will evaluate DMPEI-derivatized materials for in vivo antimicrobial efficacy. [source] Constitutive secretion of the granule chymase mouse mast cell protease-1 and the chemokine, CCL2, by mucosal mast cell homologuesCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2003J. K. Brown Summary Background The mucosal mast cell (MMC) granule-specific ,-chymase, mouse mast cell protease-1 (mMCP-1), is released systemically into the bloodstream early in nematode infection before parasite-specific IgE responses develop and TGF-,1 induces constitutive release of mMCP-1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein-1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated. Objective To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP-1, and the chemokine, CCL2. Methods MMC homologues were generated by culturing bone marrow cells in the presence of TGF-,1, IL-3, IL-9 and stem cell factor (SCF). The intracellular distribution of mMCP-1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP-1 and CCL2 was investigated using the Golgi-disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA. Results mMCP-1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP-1 was significantly inhibited (, 40%) by cycloheximide and by the Golgi-disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP-1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2. Conclusion The culture conditions that promote mMCP-1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators. [source] | ||||||||||