Home About us Contact
|
Home About us Contact | ||
|
|
||
Inflammatory Model (inflammatory + model)
Selected AbstractsAdenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] NTPDase1 governs P2X7 -dependent functions in murine macrophagesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Sébastien A. Lévesque Abstract P2X7 receptor is an adenosine triphosphate (ATP)-gated ion channel within the multiprotein inflammasome complex. Until now, little is known about regulation of P2X7 effector functions in macrophages. In this study, we show that nucleoside triphosphate diphosphohydrolase 1 (NTPDase1)/CD39 is the dominant ectonucleotidase expressed by murine peritoneal macrophages and that it regulates P2X7 -dependent responses in these cells. Macrophages isolated from NTPDase1-null mice (Entpd1,/,) were devoid of all ADPase and most ATPase activities when compared with WT macrophages (Entpd1+/+). Entpd1,/, macrophages exposed to millimolar concentrations of ATP were more susceptible to cell death, released more IL-1, and IL-18 after TLR2 or TLR4 priming, and incorporated the fluorescent dye Yo-Pro-1 more efficiently (suggestive of increased pore formation) than Entpd1+/+ cells. Consistent with these observations, NTPDase1 regulated P2X7 -associated IL-1, release after synthesis, and this process occurred independently of, and prior to, cytokine maturation by caspase-1. NTPDase1 also inhibited IL-1, release in vivo in the air pouch inflammatory model. Exudates of LPS-injected Entpd1,/, mice had significantly higher IL-1, levels when compared with Entpd1+/+ mice. Altogether, our studies suggest that NTPDase1/CD39 plays a key role in the control of P2X7 -dependent macrophage responses. [source] Expression of receptor activator of nuclear factor kappa B ligand relates to inflammatory bone resorption, with or without occlusal trauma, in ratsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2007Y. Yoshinaga Background and Objective:, Receptor activator of nuclear factor kappa B ligand (RANKL) is an important factor in osteoclast differentiation, activation and survival; however, its involvement in inflammatory bone resorption, with or without occlusal trauma, is unclear. The purpose of the present study was to investigate the distribution of RANKL-expressing cells in rat periodontium during lipopolysaccharide-induced inflammation with or without occlusal trauma. Material and Methods:, Lipopolysaccharide was injected into rat gingiva of the lower left first molar to induce inflammation. In addition, the occlusal surface of the upper left first molar of rat was raised by placing a gold inlay to induce occlusal trauma in the lower left first molars. The distribution of RANKL-expressing cells was immunohistochemically observed. Results:, In the inflammatory model, many osteoclasts were observed at the apical inter-radicular septum on day 5 and they were reduced by day 10. On the other hand, in the inflammatory model with occlusal trauma, many osteoclasts were still observed on day 10. RANKL expression was similar to the changes in osteoclast number. The expression of RANKL increased in endothelial cells, inflammatory cells and periodontal ligament cells. Conclusion:, These findings clearly demonstrated that RANKL expression on endothelial cells, inflammatory cells and periodontal ligament cells is involved in inflammatory bone resorption and the expression is enhanced by traumatic occlusion. These results suggest that RANKL expression on these cells is closely involved in the increase of osteoclasts induced by occlusal trauma. [source] Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral painNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010H. Eutamene Abstract Background, Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). Methods,Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. Key Results,In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. Conclusions & Inferences,These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C. [source] Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2001P.M. Bosio Objective To report plasma concentrations of the adhesion cell molecule P-selectin during pregnancy to determine the effect of subsequent development of hypertension and pre-eclampsia. Design A longitudinal study. Methods A longitudinal study involving 70 women followed up from early pregnancy; 20 who subsequently developed pre-eclampsia were compared with 24 who developed gestational hypertension and 26 normotensive women with normal obstetric outcome. The determination of citrate plasma soluble P-selectin levels throughout pregnancy was performed using a commercial quantitative sandwich immunoassay kit. The temporal course of plasma P-selectin in the three groups of subjects was analysed. Results There was no significant difference in mean plasma P-selectin concentration between normotensive and gestational hypertensive subjects at any stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at 10,14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean plasma P-selectin concentrations were significantly elevated by 10,14 weeks in women who later developed pre-eclampsia (P<0.001). Conclusions Our data support an inflammatory model for pre-eclampsia whereby endothelial cell activation may be secondary to a primary inflammatory response. Plasma P-selectin has significant potential as a first trimester clinical marker of pre-eclampsia. [source] RESEARCH PAPER: The antihyperalgesic effect of levetiracetam in an inflammatory model of pain in rats: mechanism of actionBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2010A Micov BACKGROUND AND PURPOSE Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain. EXPERIMENTAL APPROACH Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABAA receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective ,2 -adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam. RESULTS Levetiracetam (10,200 mg·kg,1; p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5,2 mg·kg,1; i.p.), naloxone (1,3 mg·kg,1; i.p.), methysergide (0.25,1 mg·kg,1; i.p.) and yohimbine (1,3 mg·kg,1; i.p.). CONCLUSIONS AND IMPLICATIONS These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABAA, opioid, 5-HT and ,2 -adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans. [source] | ||||||||||