Effects of Topical Corticosteroids and Nonsteroidal Anti-Inflammatory Drugs on Prostaglandin E2-Induced Aqueous Flare Elevation in Pigmented Rabbits

2003 ◽  
Vol 35 (6) ◽  
pp. 341-344 ◽  
Author(s):  
Yoriko Hayasaka ◽  
Seiji Hayasaka ◽  
Xue-Yun Zhang ◽  
Yasunori Nagaki
2003 ◽  
Vol 35 (5) ◽  
pp. 256-260 ◽  
Author(s):  
Yoriko Hayasaka ◽  
Seiji Hayasaka ◽  
Xue-Yun Zhang ◽  
Yasunori Nagaki

2004 ◽  
Vol 48 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Mohammed A. S. Alem ◽  
L. Julia Douglas

ABSTRACT Prostaglandins are now known to be produced by Candida albicans and may play an important role in fungal colonization. Their synthesis in mammalian cells is decreased by inhibitors of the cyclooxygenase isoenzymes required for prostaglandin formation. In the present study, a catheter disk model system was used to investigate the effects of nonsteroidal anti-inflammatory drugs (all cyclooxygenase inhibitors) on biofilm formation by three strains of C. albicans. Seven of nine drugs tested at a concentration of 1 mM inhibited biofilm formation. Aspirin, etodolac, and diclofenac produced the greatest effects, with aspirin causing up to 95% inhibition. Celecoxib, nimesulide, ibuprofen, and meloxicam also inhibited biofilm formation, but to a lesser extent. Aspirin was active against growing and fully mature (48-h) biofilms; its effect was dose related, and it produced significant inhibition (20 to 80%) at pharmacological concentrations. Simultaneous addition of prostaglandin E2 abolished the inhibitory effect of 25 or 50 μM aspirin. At 1 mM, aspirin reduced the viability of biofilm organisms to 1.9% of that of controls. Surviving cells had a wrinkled appearance, as judged by scanning electron microscopy, and consisted of both yeasts and hyphae. Treatment with other cyclooxygenase inhibitors, such as etodolac, resulted in biofilms that consisted almost entirely of yeast cells. In conventional assays for germ tube formation, these drugs produced significant inhibition, whereas aspirin had little effect. Our findings suggest that cyclooxygenase-dependent synthesis of fungal prostaglandin(s) is important for both biofilm development and morphogenesis in C. albicans and may act as a regulator in these physiological processes. Our results also demonstrate that aspirin possesses potent antibiofilm activity in vitro and could be useful in combined therapy with conventional antifungal agents in the management of some biofilm-associated Candida infections.


2003 ◽  
Vol 31 (05) ◽  
pp. 729-738 ◽  
Author(s):  
Yasunori Nagaki ◽  
Seiji Hayasaka ◽  
Tomohiro Abe ◽  
Xue-Yun Zhang ◽  
Yoriko Hayasaka ◽  
...  

The purpose of this study was to evaluate the effects of extracts of Coptidis rhizoma, Phellodendri cortex and Gardeniae fructus, which are medicinal herbs in Orengedoku-to (Huanglin-Jie-Du-Tang in Chinese), and crocetin (a major component of Gardeniae fructus) on experimental elevation of aqueous flare in pigmented rabbits. To produce aqueous flare elevation, 0.5 μg/kg lipopolysaccharide (LPS) was injected into the ear vein, or prostaglandin E2 (PGE2) 25 μg/ml, was applied to the cornea by means of a glass cylinder. Animals were pretreated by oral administration of 150 g/day of food containing 0.15% (w/w) extract powder of Coptidis rhizoma, 0.10% (w/w) extract powder of Phellodendri cortex or 0.15% (w/w) extract powder of Gardeniae fructus for 4 days, or by intravenous injection of crocetin, 0.3, 3, 30 or 300 μg/kg, 30 minutes before aqueous flare elevation. Aqueous flare was measured with a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. The AUC of LPS- and PGE2-induced aqueous flare elevation was 4685 and 1386 arbitrary units, respectively. Pretreatment by oral administration of 0.15% (w/w) extract of Coptidis rhizoma or 0.10% (w/w) extract of Phellodendri cortex did not inhibit LPS-induced aqueous flare elevation. Pretreatment by oral administration of 0.15% extract of Gardeniae fructus suppressed LPS-induced aqueous flare elevation (AUC: 1411 arbitrary units). Pretreatment by intravenous injection of 3, 30 or 300 μg/kg of crocetin-inhibited LPS-induced aqueous flare elevation in a dose-dependent manner. Pretreatment with 3 or 30 μg/kg of crocetin did not inhibit PGE2-induced aqueous flare elevation, but 300 μg/kg of crocetin inhibited PGE2-induced aqueous flare elevation (AUC: 918 arbitrary units).


Reproduction ◽  
2001 ◽  
pp. 3-19 ◽  
Author(s):  
RW Kelly ◽  
AE King ◽  
HO Critchley

Cytokines within endometrium participate in both menstruation and implantation but also contribute to the defence mechanisms of the mucosal epithelium. Endometrium is under the control of steroid hormones, particularly progesterone and, thus, control of cytokines by this steroid is important. Although appreciable numbers of progesterone receptors are not found in endometrial leucocytes, progesterone can modulate cytokines by acting on uterine cells expressing the receptor. The NFkappaB pathway is important in the control of cytokine synthesis and can modulate production of chemokines, matrix metalloproteinases and the inducible prostaglandin synthesis enzyme COX-2. NFkappaB activity can be inhibited by progesterone by either stimulating synthesis of IkappaB, the molecule that restrains NFkappaB in the cytosol, or after binding to the nuclear receptor, competing with NFkappaB for recognition sites on the relevant gene. In this way, progesterone can limit pro-inflammatory pathways. The major palliatives for endometrial dysfunctions such as menorrhagia and dysmenorrhoea have been the non-steroidal anti-inflammatory drugs that inhibit prostaglandin synthesis. Prostaglandins have major effects on cytokine production but the direct action of prostaglandin E on leucocytes is not a pro-inflammatory response but is to stimulate interleukin 10 and inhibit interleukin 12 synthesis. The likely effect of the non-steroidal anti-inflammatory drugs is on the cells surrounding the small blood vessels, where a synergistic action between prostaglandin and chemokine will induce leucocyte entry and activation leading to lysis of connective tissue and menstruation. At the time of implantation, tight control of cytokine synthesis is required. Although leukaemia inhibitory factor is essential to implantation, the mouse knockout models show that the prostaglandin system is also essential but that there are mutually supportive pathways that compensate for the knockout of many cytokines.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jaehwi Lee ◽  
Man Hee Rhee ◽  
Eunji Kim ◽  
Jae Youl Cho

BAY 11-7082 (BAY) is an inhibitor ofκB kinase (IKK) that has pharmacological activities that include anticancer, neuroprotective, and anti-inflammatory effects. In this study, BAY-pharmacological target pathways were further characterized to determine how this compound simultaneously suppresses various responses. Primary and cancerous (RAW264.7 cells) macrophages were activated by lipopolysaccharide, a ligand of toll-like receptor 4. As reported previously, BAY strongly suppressed the production of nitric oxide, prostaglandin E2, and tumor necrosis factor-αand reduced the translocation of p65, major subunit of nuclear factor-κB, and its upstream signaling events such as phosphorylation of IκBα, IKK, and Akt. In addition, BAY also suppressed the translocation and activation of activator protein-1, interferon regulatory factor-3, and signal transducer and activator of transcription-1 by inhibiting the phosphorylation or activation of extracellular signal-related kinase, p38, TANK-binding protein, and Janus kinase-2. These data strongly suggest that BAY is an inhibitor with multiple targets and could serve as a lead compound in developing strong anti-inflammatory drugs with multiple targets in inflammatory responses.


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