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Paw
Kinds of Paw Terms modified by Paw Selected AbstractsAntinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2005Vinícius M. Gadotti This study examined the antinociceptive effect of Bauhinia microstachya (Leguminosae), a native plant widely distributed in the South of Brazil, in several chemical and mechanical models of pain. The methanolic extract (ME) from B. microstachya (3,30 mg kg,1, i.p.) and the isolated compound quercitrin (1,10 mg kg,1, i.p.), given 30 min earlier, produced a dose-dependent inhibition of acetic-acid-induced visceral pain in mice, with a mean ID50 value (dose necessary to reduce the nociceptive response by 50% relative to the control value) of 7.9 and 2.4 mg kg,1, respectively. The ME of B. microstachya (3,100 mg kg,1, i.p., 30 min earlier) also caused a dose-dependent inhibition of capsaicin-induced pain, with a mean ID50 value of 18.8 mg kg,1. Moreover, the ME (3,100 mg kg,1, i.p., 30 min earlier) produced marked inhibition of both phases of formalin-induced pain, with mean ID50 values for the neurogenic and the inflammatory phases of 30.3 and 17.2 mg kg,1, respectively. In addition, the ME of B. microstachya (3,300 mg kg ,1, i.p., 30 min earlier) inhibited, in a graded manner, the hyperalgesia induced by bradykinin (3.2 ,g/paw), substance P (13.5 ,g/paw), carrageenan (300 ,g/paw), capsaicin (100 ,g/paw) and adrenaline (100ng/paw) in the rat paw, with mean ID50 values of 20.5, 17.9, 101.8, 54.2 and 99.7 mg kg,1, respectively. Taken together, these data demonstrate that ME of B. microstachya elicited a pronounced antinociceptive action against several chemical and mechanical models of pain in mice and rats. The precise mechanism responsible for the antinociceptive effect of the extract still remains unclear, but seems to be partly related to modulation of the release or action of pro-inflammatory mediators involved in the models of pain used. Finally, the flavonoid quercitrin isolated from this plant appears to contribute for the antinociceptive property of the methanolic extract. [source] Amazon drought and its implications for forest flammability and tree growth: a basin-wide analysisGLOBAL CHANGE BIOLOGY, Issue 5 2004Daniel Nepstad Abstract Severe drought in moist tropical forests provokes large carbon emissions by increasing forest flammability and tree mortality, and by suppressing tree growth. The frequency and severity of drought in the tropics may increase through stronger El Nińo Southern Oscillation (ENSO) episodes, global warming, and rainfall inhibition by land use change. However, little is known about the spatial and temporal patterns of drought in moist tropical forests, and the complex relationships between patterns of drought and forest fire regimes, tree mortality, and productivity. We present a simple geographic information system soil water balance model, called RisQue (Risco de Queimada , Fire Risk) for the Amazon basin that we use to conduct an analysis of these patterns for 1996,2001. RisQue features a map of maximum plant-available soil water (PAWmax) developed using 1565 soil texture profiles and empirical relationships between soil texture and critical soil water parameters. PAW is depleted by monthly evapotranspiration (ET) fields estimated using the Penman,Monteith equation and satellite-derived radiation inputs and recharged by monthly rain fields estimated from 266 meteorological stations. Modeled PAW to 10 m depth (PAW10 m) was similar to field measurements made in two Amazon forests. During the severe drought of 2001, PAW10 m fell to below 25% of PAWmax in 31% of the region's forests and fell below 50% PAWmax in half of the forests. Field measurements and experimental forest fires indicate that soil moisture depletion below 25% PAWmax corresponds to a reduction in leaf area index of approximately 25%, increasing forest flammability. Hence, approximately one-third of Amazon forests became susceptible to fire during the 2001 ENSO period. Field measurements also suggest that the ENSO drought of 2001 reduced carbon storage by approximately 0.2 Pg relative to years without severe soil moisture deficits. RisQue is sensitive to spin-up time, rooting depth, and errors in ET estimates. Improvements in our ability to accurately model soil moisture content of Amazon forests will depend upon better understanding of forest rooting depths, which can extend to beyond 15 m. RisQue provides a tool for early detection of forest fire risk. [source] Atomistic characterization of structural and elastic properties of auxetic crystalline SiO2PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2007Hajime Kimizuka Abstract The structural and elastic changes with volume expansion in , -quartz and , -cristobalite, the typical polymorphs of silicon dioxide (SiO2), have been studied through first-principles calculations using the projector-augmented-wave (PAW) method, with particular emphasis on their negative Poisson's ratio behavior under negative pressure. The dominant mechanism of expansion is the increase of the Si,O,Si angles within their crystalline structures, whereas the SiO4 tetrahedron undergoes only a slight distortion. We provide theoretical ab initio results for a complete set of independent elastic constants of quartz and cristobalite with volume expansion. The present simulations confirm that the negative Poisson's ratio behavior is enhanced in the expansive phases of both polymorphs under negative pressures, with retaining strong elastic anisotropy. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Haemodynamic changes during positive-pressure ventilation in childrenACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2005A. Kardos Background:, Positive-pressure ventilation may alter cardiac function. Our objective was to determine with the use of impedance cardiography (ICG) whether altering airway pressure modifies the central haemodynamics in mechanically ventilated children with no pulmonary pathology. Central venous saturation (ScvO2) was measured as an indicator of tissue perfusion. Methods:, Twelve children between 7 and 65 months of age, requiring mechanical ventilation as a consequence of a non-pulmonary disease, were enrolled in the study. All patients had a central venous line as a part of their routine management. Using pressure controlled ventilation (PCV) the baseline PEEP value of 5 cmH2O (Pb5) was increased to 10 cmH2O (Pi10) and then to 15 cmH2O (Pi15). After Pi15, PEEP was decreased to 10 (Pd10) and then to 5 cmH2O (Pd5). Each time period lasted 5 min heart rate (HR), mean arterial blood pressure (MABP), central venous pressure (CVP), end-tidal carbon dioxide (ETCO2), mean airway pressure (Paw), stroke volume index (SVI), cardiac index (CI) and central venous oxygen saturation (ScvO2) were recorded at the end of the five periods. Results:, The values of CI did not change when 10 and 15 cmH2O of PEEP were applied. Elevation of PEEP and thus Paw caused slight but not significant reductions in SVI and ScvO2 as compared to the baseline (Tb5). After reducing PEEP in Td5 we found statistically significant elevations of SVI and CI, as compared to Ti15 heart rate, ETCO2 and MABP remained unchanged. Conclusion:, We did not find significant haemodynamic changes following PEEP elevation in ventilated children, as measured using impedance cardiography. Reducing the value of PEEP to 5 cmH2O resulted in statistically significant SVI elevations. The values of ScvO2 remained unaffected. [source] Evaluation of pelvic wedge for gynaecological laparoscopyANAESTHESIA, Issue 10 2008P. Kundra Summary Seventy-eight ASA 1 and 2 women scheduled for elective diagnostic laparoscopy under general anaesthesia were randomly allocated into two groups. Patients were either positioned with a 20° Trendelenberg tilt (group T) or with a wedge placed under the pelvis (group W). A standard general anaesthetic technique was used in all patients. The endoscopic view of pelvic organs was graded on a four-point scale by the operating surgeon. Heart rate (HR), mean arterial pressure (MAP), SpO2, and peak airway pressure (Paw) were continuously measured. Significantly more patients (77%) in group W had grade 1 view (clear view of pelvic organs without additional manoeuvres) when compared with group T (46%). Mean Paw increased significantly in group T when compared with group W. The use of a pelvic wedge provides a better view of pelvic viscera than 20° Trendelenberg tilt during gynaecological laparoscopy. [source] Antinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2005Vinícius M. Gadotti This study examined the antinociceptive effect of Bauhinia microstachya (Leguminosae), a native plant widely distributed in the South of Brazil, in several chemical and mechanical models of pain. The methanolic extract (ME) from B. microstachya (3,30 mg kg,1, i.p.) and the isolated compound quercitrin (1,10 mg kg,1, i.p.), given 30 min earlier, produced a dose-dependent inhibition of acetic-acid-induced visceral pain in mice, with a mean ID50 value (dose necessary to reduce the nociceptive response by 50% relative to the control value) of 7.9 and 2.4 mg kg,1, respectively. The ME of B. microstachya (3,100 mg kg,1, i.p., 30 min earlier) also caused a dose-dependent inhibition of capsaicin-induced pain, with a mean ID50 value of 18.8 mg kg,1. Moreover, the ME (3,100 mg kg,1, i.p., 30 min earlier) produced marked inhibition of both phases of formalin-induced pain, with mean ID50 values for the neurogenic and the inflammatory phases of 30.3 and 17.2 mg kg,1, respectively. In addition, the ME of B. microstachya (3,300 mg kg ,1, i.p., 30 min earlier) inhibited, in a graded manner, the hyperalgesia induced by bradykinin (3.2 ,g/paw), substance P (13.5 ,g/paw), carrageenan (300 ,g/paw), capsaicin (100 ,g/paw) and adrenaline (100ng/paw) in the rat paw, with mean ID50 values of 20.5, 17.9, 101.8, 54.2 and 99.7 mg kg,1, respectively. Taken together, these data demonstrate that ME of B. microstachya elicited a pronounced antinociceptive action against several chemical and mechanical models of pain in mice and rats. The precise mechanism responsible for the antinociceptive effect of the extract still remains unclear, but seems to be partly related to modulation of the release or action of pro-inflammatory mediators involved in the models of pain used. Finally, the flavonoid quercitrin isolated from this plant appears to contribute for the antinociceptive property of the methanolic extract. [source] Peripheral antinociceptive effect of pertussis toxin: activation of the arginine/NO/cGMP/PKG/ ATP-sensitive K+ channel pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Gerly A. C. Brito Abstract The aim of the present study was to determine the effect of pertussis toxin (PTX) on inflammatory hypernociception measured by the rat paw pressure test and to elucidate the mechanism involved in this effect. In this test, prostaglandin E2 (PGE2) administered subcutaneously induces hypernociception via a mechanism associated with neuronal cAMP increase. Local intraplantar pre-treatment (30 min before), and post-treatment (5 min after) with PTX (600 ng/paw1, in 100 µL) reduced hypernociception induced by prostaglandin E2 (100 ng/paw, in 100 µL, intraplantar). Furthermore, local intraplantar pre-treatment (30 min before) with PTX (600 ng/paw, in 100 µL) reduced hypernociception induced by DbcAMP, a stable analogue of cAMP (100 µg/paw, in 100 µL, intraplantar), which indicates that PTX may have an effect other than just Gi/G0 inhibition. PTX-induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L-NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP-sensitive K+ channel (Kir6) blockers (glybenclamide and tolbutamide). In addition, PTX was shown to induce nitric oxide (NO) production in cultured neurons of the dorsal root ganglia. In conclusion, this study shows a peripheral antinociceptive effect of pertussis toxin, resulting from the activation of the arginine/NO/cGMP/PKG/ATP-sensitive K+ channel pathway. [source] Hemidesmosome protein dynamics in live epithelial cellsCYTOSKELETON, Issue 2 2003Daisuke Tsuruta Abstract Hemidesmosomes mediate stable anchorage of epithelial cells to laminin-5 in the basement membrane zone and have been likened to spot-welds. Indeed, it has been assumed that hemidesmosomes are not dynamic, at least when compared to other matrix adhesion sites including focal contacts. We tested this notion by monitoring the fate of green fluorescent protein (GFP)-tagged human integrin ,4 subunit (GFP-h,4) and GFP-tagged 180-kD human bullous pemphigoid (BP) autoantigen (GFP-BP180) in live cultures of 804G cells that assemble numerous mature hemidesmosomes. In subconfluent 804G cells, both GFP-h,4 and GFP-BP180 protein clusters are not stable but assemble into and disassemble out of cat paw,like arrays at a relatively rapid rate. In confluent populations of 804G cells, although some cat paw,like clusters of both GFP-h,4 and GFP-BP180 are stable over periods of >60 min, other GFP-h,4 and GFP-BP180 protein arrays form and/or disappear during the same time period. Moreover, individual labeled particles show considerable motility in the plane of the membrane. Fluorescence recovery after photobleaching analyses provide a further indication of the dynamics of hemidesmosome proteins. In particular, bleached GFP-h,4 protein clusters in confluent cells recover signal within about 30 min, indicating that there is a relatively rapid turnover of hemidesmosome components in protein arrays clustered along the substratum attached surface of a cell. The rate of recovery is dependent on an intact microfilament system. In sharp contrast, bleached GFP-BP180 protein clusters in confluent cells fail to recover signal even when observed for longer than 60 min. To evaluate hemidesmosome protein dynamics in motile cells, we monitored GFP-h,4 and GFP-BP180 in 804G cells populating scrape wound sites in vitro. In these migratory cells, which lack mature hemidesmosomes, integrin ,4 subunit and BP180 protein clusters progressively assemble and disassemble into linear and cat-paw arrays. In summary, hemidesmosome protein clusters, like their counterparts in focal contacts, are dynamic. We discuss these results in relation to hemidesmosome functions. Cell Motil. Cytoskeleton 54:122,134, 2003. © 2003 Wiley-Liss, Inc. [source] Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Pascal Barnéoud Abstract We have examined the behavioural consequences of a partial unilateral dopaminergic denervation of the rat striatum. This partial lesion was obtained by an intrastriatal 6-hydroxy-dopamine injection (6-OHDA, 20 or 10 ,g divided between two injection sites) and was compared with a unilateral complete lesion resulting from an injection of 6-OHDA (2 × 6 ,g) into the medial forebrain bundle. Quantification of striatal dopamine (DA) and its metabolites, and the immunohistochemical evaluation of the nigrostriatal DA system confirmed the complete and partial lesions. Animals with complete striatal denervation displayed both apomorphine- and amphetamine-induced rotations whereas the partial denervation elicited amphetamine-induced rotations only. However, the rates of amphetamine-induced rotation were not correlated with the size of the lesion. In contrast, the paw-reaching impairments were significantly correlated with the striatal dopaminergic depletion. When evaluated in the staircase test, animals with partial denervation were impaired exclusively for the paw contralateral to the side of the lesion. This motor deficit (50,75%) included all components of the skilled paw use (i.e. attempt, motor coordination and success) and was observed at least 12 weeks after the lesion. However, these animals were able to perform normal stepping adjustments with the impaired paw, indicating that the partial lesion induced a coordination deficit of the paw rather than a deficit of movement initiation. After a complete lesion, stepping adjustments of the contralateral paw were dramatically impaired (by 80%), an akinesia which almost certainly accounted for the great deficit in skilled paw use. The paw-reaching impairments resulting from the partial striatal denervation are proposed as a model of the early symptoms of Parkinson's disease and may be useful for the development of restorative therapies. [source] Inhibition of scratching behaviour caused by contact dermatitis in histidine decarboxylase gene knockout miceEXPERIMENTAL DERMATOLOGY, Issue 3 2005M. Seike Abstract:, A neuronal system dedicated to itch consists of primary afferent and spinothalamic projection neurons. Histamine is thought to be one of the main mediators for the transmission of itch sensation. However, there are little available information on the role of histamine in scratching behaviour and sensory transmission of atopic dermatitis and chronic eczema. In the present study, the role of histamine in scratching behaviour and neural conduction of sensation in the chronic eczema model was investigated by using l-histidine decarboxylase (HDC) gene knockout mice lacking histamine. The chronic contact dermatitis was induced with daily application of diphenylcyclopropenone (DCP) on a hind paw of HDC (+/+) and HDC (,/,) mice for 2 months. The observation of scratching behaviour and the hot-plate test were performed in both mice. Histological studies were performed in the skin and spinal cord tissues. Histological examination revealed that both HDC (+/+) and HDC (,/,) mice displayed the similar extent of inflammatory cell infiltration, hyperplastic epidermis and newly spreading of neuronal processes in the skin tissue. Scratching behaviour was exclusively induced in HDC (+/+) mice, whereas it was barely observed in HDC (,/,) mice. The expression of c-Fos was specifically upregulated in HDC (+/+) mice in lamina I of the spinal dorsal horn following repeated DCP application. Scratching behaviour in chronic contact dermatitis in mice was thought mainly mediated with histamine. The afferent pathway of sensation in chronic contact dermatitis model may connect with the central nervous system through lamina I of the spinal dorsal horn. [source] Proteinase-activated receptor-1 is an anti-inflammatory signal for colitis mediated by a type 2 immune responseINFLAMMATORY BOWEL DISEASES, Issue 9 2005Nicolas Cenac PhD Abstract Background: Activation of colonic proteinase activated receptor-1 (PAR1) provokes colonic inflammation and increases mucosal permeability in mice. The mechanism of inflammation is not neurogenic like in the paw of rats but depends on PAR1 -mediated activation monocytic cells. PAR1 activation in the colon increases the release of lymphocyte T helper-1 (TH1) cytokines. Moreover, PAR1 expression is increased in biopsies from patients with inflammatory bowel disease, and its activation during TH1-mediated colitis in mice increases all of the hallmarks of inflammation. Methods: This study aimed to characterize the effects of PAR1 activation in oxazolone-mediated colitis, involving a TH2 cytokine profile. Results: Intracolonic administration of oxazolone increased myeloperoxidase activity, damage score, and interleukin (IL)-4, IL-10, tumor necrosis factor ,, and IL-1, mRNA expression but lowered interferon-, mRNA expression, indicating colonic inflammation of a TH2 profile. The concurrent intracolonic administration of a PAR1 agonist in oxazolone-treated mice inhibited colitis, resulting in a reduction of myeloperoxidase activity, damage score, and inflammatory cytokine mRNA expression. Using PAR1 -deficient mice, we confirmed that the anti-inflammatory effects of PAR1 agonists were mediated by PAR1. Moreover, in PAR1 -deficient mice or in mice treated with a PAR1 antagonist, oxazolone-induced colitis was exacerbated, showing an endogenous modulatory role for PAR1 in this TH2 cytokine profile of colitis. Conclusions: Thus, as opposed to a previously shown proinflammatory role for PAR1 in a TH1 cytokine-mediated colitis, our new data show anti-inflammatory role for PAR1 activation in the setting of TH2 cytokine colitis model. [source] Reactive oxygen species in rats with chronic post-ischemia painACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009K. H. KWAK Background: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw. Methods: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague,Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester (l -NAME, 10 mg/kg), or SOD (4000 U/kg)+l -NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats. Results: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l -NAME, which were used to investigate the roles of superoxide (O2 ,,) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks. Conclusions: Our findings suggest that O2 ,, and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects. [source] The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] Microinjection of morphine into thalamic nucleus submedius depresses bee venom-induced inflammatory pain in the ratJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Jie Feng Previous studies have provided evidence of the existence of a pain modulatory feedback pathway consisting of thalamic nucleus submedius (Sm),ventrolateral orbital cortex-periaqueductal grey pathway, which is activated during acute pain and leads to depression of transmission of nociceptive information in the spinal dorsal horn. The aim of this study was to test the hypothesis that morphine microinjection into the Sm decreased spontaneous pain and bilateral thermal hyperalgesia, as well as ipsilateral mechanical allodynia, induced by subcutaneous injections of bee venom into the rat hind paw. Morphine (1.0, 2.5 or 5.0 m,g in 0.5 ,L) injected into the Sm, contralateral to the bee venominjected paw, depressed spontaneous nociceptive behaviour in a dose-dependent manner. Furthermore, morphine significantly decreased bilateral thermal hyperalgesia and ipsilateral mechanical allodynia 2 h after bee venom injection. These morphine-induced effects were antagonized by 1.0 ,g naloxone (an opioid antagonist) microinjected into the Sm 5 min before morphine administration. The results provided further support for the important role of the Sm and Sm-opioid receptors in inhibiting nociceptive behaviour and indicated for the first time that Sm opioid receptors were also effective in inhibiting the hypersensitivity provoked by bee venom-induced inflammation. [source] Antinociceptive and anti-inflammatory effects of the essential oil from Eremanthus erythropappus leavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2008Orlando V. Sousa The chemical composition of the essential oil from air-dried leaves of Eremanthus erythropappus was studied. The main compounds were ,-pinene (23.24%), ,-caryophyllene (22.92%), ,-myrcene (10.03%) and germacrene D (9.40%). The essential oil had an LD50 of 2.90 gkg,1 in mice. Doses of 200 and 400 mgkg,1 inhibited 10.69% and 27.06% of acetic-acid-induced writhing in mice, respectively. In the formalin-induced nociception test in mice, the essential oil inhibited the first phase of paw licking by 29.13% (400 mgkg,1) and the second phase by 32.74% (200 mgkg,1) and 37.55% (400 mgkg,1). In the hot-plate test in mice, doses of 200 mgkg,1 and 400 mgkg,1 significantly increased the reaction time after 30, 60 and 90 min of treatment. Doses of 200 and 400 mgkg,1 inhibited carrageenan-induced paw oedema in rats by 15.18% and 36.61%, respectively. Doses of 200 and 400 mgkg,1 administered 4 h before intra-pleural injection of carrageenan significantly reduced exudate volume (by 20.20% and 48.70%, respectively) and leucocyte mobilization (by 5.88% and 17.29%, respectively). These results demonstrate that E. erythropappus has analgesic and anti-inflammatory properties, supporting the use of this plant in folk medicine. [source] The inhibition of paw oedema formation caused by the oil of Copaifera multijuga Hayne and its fractionsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2006Valdir F. Veiga Junior Two oils exuded from a Copaifera multijuga Hayne tree (Leguminosae-Caesalpinoideae), collected from the same plant, but in different periods of the year, and the hexanic, dichloromethanic and methanolic fractions of one of these oils were analysed by high-resolution gas chromatography (HRGC) and HRGC coupled with mass spectrometry (HRGC-MS). In addition, the in-vivo preliminary anti-oedematogenic actions of the oil and some fractions of it were assessed against carrageenan- and bradykinin-induced oedema formation in the rat paw. Twenty-seven sesquiterpenes and six diterpenes were identified, ,-caryophyllene, ,-copaene and copalic acid being the main components. The dichloromethanic and methanolic fractions obtained from C. multijuga oil given by the intraperitoneal route caused a significant inhibition of paw oedema caused by carrageenan with inhibition of 49 ± 13% and 64 ± 9 %, respectively. Likewise, dexamethasone (the positive control drug) also greatly inhibited carrageenan-induced paw oedema formation (60 ± 4% at 2 h). The hexanic fraction also significantly inhibited (50 ± 6%) the paw oedema formation caused by bradykinin. These results suggest the presence of still non-identified active terpene compounds in the oil of C. multijuga that exhibit anti-oedematogenic properties. Of note, the yield of these compounds and the pharmacological actions of the oil, exhibited great seasonal variations, a relevant aspect that should be carefully observed for the correct medicinal use of this plant by the population. [source] Antinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leavesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2005Vinícius M. Gadotti This study examined the antinociceptive effect of Bauhinia microstachya (Leguminosae), a native plant widely distributed in the South of Brazil, in several chemical and mechanical models of pain. The methanolic extract (ME) from B. microstachya (3,30 mg kg,1, i.p.) and the isolated compound quercitrin (1,10 mg kg,1, i.p.), given 30 min earlier, produced a dose-dependent inhibition of acetic-acid-induced visceral pain in mice, with a mean ID50 value (dose necessary to reduce the nociceptive response by 50% relative to the control value) of 7.9 and 2.4 mg kg,1, respectively. The ME of B. microstachya (3,100 mg kg,1, i.p., 30 min earlier) also caused a dose-dependent inhibition of capsaicin-induced pain, with a mean ID50 value of 18.8 mg kg,1. Moreover, the ME (3,100 mg kg,1, i.p., 30 min earlier) produced marked inhibition of both phases of formalin-induced pain, with mean ID50 values for the neurogenic and the inflammatory phases of 30.3 and 17.2 mg kg,1, respectively. In addition, the ME of B. microstachya (3,300 mg kg ,1, i.p., 30 min earlier) inhibited, in a graded manner, the hyperalgesia induced by bradykinin (3.2 ,g/paw), substance P (13.5 ,g/paw), carrageenan (300 ,g/paw), capsaicin (100 ,g/paw) and adrenaline (100ng/paw) in the rat paw, with mean ID50 values of 20.5, 17.9, 101.8, 54.2 and 99.7 mg kg,1, respectively. Taken together, these data demonstrate that ME of B. microstachya elicited a pronounced antinociceptive action against several chemical and mechanical models of pain in mice and rats. The precise mechanism responsible for the antinociceptive effect of the extract still remains unclear, but seems to be partly related to modulation of the release or action of pro-inflammatory mediators involved in the models of pain used. Finally, the flavonoid quercitrin isolated from this plant appears to contribute for the antinociceptive property of the methanolic extract. [source] Investigations into the antinociceptive activity of Sapindus trifoliatus in various pain modelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2004D. K. Arulmozhi The effect of the aqueous extract of Sapindus trifoliatus (ST) on chemical, thermal-induced pain, nitroglycerin-induced hyperalgesia and pain on inflamed tissue was investigated. The extract (20 and 100 mg kg,1, i.p.) significantly inhibited acetic-acid-induced abdominal constrictions, formalin-induced pain licking and hotplate-induced pain in mice. Furthermore, the extract significantly increased the response latencies of nitroglycerin-induced hyperalgesia by the tail-flick method and mechanical pain on carrageenan-induced inflamed paw in rats. The data suggest that ST has an inhibitory activity on both peripheral and central pain mechanisms and has a modulatory role in NO-mediated nociceptive transmission. [source] Effects of Naturally Occurring Stilbene Glucosides from Medicinal Plants and Wine, on Tumour Growth and Lung Metastasis in Lewis Lung Carcinoma-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000YOSHIYUKI KIMURA Stilbene glucosides are naturally occurring phytoalexins, found in a variety of medicinal plants. Among the stilbene derivatives, resveratrol 3- O -D-glucoside (piceid) is found in grapes and wine. We studied the effects of stilbene glucosides isolated from medicinal plants and grapes on tumour growth and lung metastasis in mice bearing highly metastastic Lewis lung carcinoma (LLC) tumours. We also studied the inhibitory effects of stilbene glucosides on differentiation of human umbilical vein endothelial cells (HUVECs) to form a capillary network. Tumour growth in the right hind paw and lung metastasis were inhibited by oral administration of the stilbene glucosides, piceid and 2,3,5,4,-tetrahydroxystilbene-2- O -D-glucoside for 33 consecutive days, in LLC-bearing mice. As the number of CD8+ and NK1.1+ T cells in the spleen was not affected, the inhibitory effects of these stilbene glucosides on tumour growth and lung metastasis could not be explained by natural killer or cytotoxic T lymphocyte activation. Piceid inhibited the DNA synthesis in LLC cells at a concentration of 1000 ,m, but not at lower concentrations (10,100 ,M). 2,3,5,4,-Tetra-hydroxystilbene-2- O -D-glucoside also inhibited DNA synthesis in LLC cells (IC50 81 ,M). In addition, both stilbene glucosides inhibited the formation of capillary-like tube networks (angiogenesis) of HUVECs at concentrations of 100 to 1000 ,M. We suggest that the antitumour and antimetastatic activity of the stilbene glucosides, piceid and 2,3,5,4,-tetrahydroxystilbene-2- O -D-glucoside, might be due to the inhibition of DNA synthesis in LLC cells and angiogenesis of HUVECs. [source] Inflammatory Pain Reduction In Rats By Local Treatment With oATP, A Selective Inhibitor Of P2X7 ATP ReceptorJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001G Dell'Antonio Peptide neurotransmitters, as substance P or ATP, are released during inflammatiory processes by the nerve endings of sensory fibers. ATP is also released from the cytoplasm of damaged cells at the site of inflammation. It acts at the level of many P2X subtypes of purinoreceptors. The receptor for extracellular ATP named P2Z/P2X7 is selectively blocked by the periodate oxidized ATP (oATP). We have hypothesized that P2X subunits present on peripheral sensory nerve terminals, able to initiate a nociceptive signal, could be blocked by local treatment with oATP, so inducing pain relief. Male inbred Fisher rats weighing about 250 g were used. Unilateral inflammation into rat hind paw was induced by intraplantar injection of Freund's complete adjuvant (FCA). The following signs of inflammation, from 3 to 48 h after FCA injection, were detected: increased paw volume, increased paw temperature and hyperalgesia. The latter was evaluated using an algesiometric test wich measured the paw pressure threshold (PPT, expressed in g). We treated some rats, bearing paw inflammation by 12 h, with local injection of 56 ,M oATP. We showed a significant reduction of hyperalgesia in treated rats (PPT = 190 ± 2.3 in inflamed paw of oATP treated vs. PPT = 60 ± 1.6 in inflamed paw of untreated rats, at 60 min following oATP innoculation). We showed also that treatment with oATP was more efficient than treatment with diclofenac in reducing local inflammatory pain (PPT expressed as percentage of the maximum possible effect = 60 ± 0.5, at 120 min following intraplantar administration of oATP, vs. 25 ± 1.9 at the same time following intraplantar administration of diclofenac). The use of polyclonal antibody anti P2X7 receptor to perform immunohistochemical analysis of inflamed tissue, showed a reduction of receptor expression at the level of nerve endings in sections obtained from rat paw treated with oATP with respect to sections obtained from untreated rats. Such an effect was independent on the recruitment of immunocytes in inflamed tissue. Our results demonstrate that ATP exerts a key role in the pathophysiology of peripheral inflammation and that oATP may be effective in treating inflammatory pain. [source] Effects Of Topically Applied Capsaicin Cream On Neurogenic Inflammation And Thermal Sensitivity In RatsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000M. Yoshimura The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism. [source] Cold Exposure Enhances Tactile Allodynia Transiently In Mononeuropathic RatsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000T. Kauppila A laser and erythrosin-B-induced sciatic nerve injury decreases thresholds of a mechanically induced paw withdrawal reflex and enhances cold-induced withdrawal behavior of the affected limb. Exposure of the affected paw to a normally innocuous cold stimulus results in a transient decrease in the threshold of the mechanically evoked paw withdrawal reflex in neuropathic but not in intact rats. The present data suggest that in an experimental neuropathic state a normally innocuous cold stimulus may further sensitize spinally mediated withdrawal reflexes to stimuli of another stimulus modality, in this case, to innocuous tactile stimuli. Therefore, testing mechanical allodynia in neuropathic rats immediately after testing cold allodynia may produce artifactual results. [source] Effect of crocin on the morphine-induced antinociception in the formalin test in ratsPHYTOTHERAPY RESEARCH, Issue 3 2010Esmaeal Tamaddonfard Abstract In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra-plantar (i.pl.) injection of formalin (50,,L, 1%), and the time spent licking and biting of the injected paw was measured for 1,h. Formalin induced a marked biphasic (first phase: 0,5,min and second phase: 15,45,min) pain response. Morphine (1,mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2,mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2,mg/kg) significantly (p < 0.05) prevented morphine (1,mg/kg)-induced antinociception. Crocin at doses of 50, 100 and 200,mg/kg significantly (p < 0.05) attenuated pain. Crocin (100,mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1,mg/kg, s.c.)-induced antinociception. Naloxone (2,mg/kg) did not reverse the suppressive effect of crocin (100,mg/kg) on pain. Crocin at a dose of 400,mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone-sensitive mechanism produced analgesia. Crocin produced a dose-dependent antinociceptive effect. In addition, crocin increased morphine-induced antinociception, but naloxone did not change the antinociceptive effect of crocin. Copyright © 2009 John Wiley & Sons, Ltd. [source] Antipyretic and analgesic activities of Caesalpinia bonducella seed kernel extractPHYTOTHERAPY RESEARCH, Issue 5 2005P. Archana Abstract Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders. Copyright © 2005 John Wiley & Sons, Ltd. [source] Analgesic and antiinflammatory properties of Sideritis lotsyi var. MascaensisPHYTOTHERAPY RESEARCH, Issue 3 2002Margarita Hernández-Pérez Abstract The antiinflammatory, analgesic and antimicrobial activities of crude ethanol extracts of Sideritis lotsyi var. mascaensis (Lamiaceae), and chloroform and aqueous fractions were evaluated in mice using paw and ear oedema induced by carrageenan and 12-o-tetradecanoyl-phorbol-acetate (TPA), respectively, as inflammation models, the writhing test induced by acetic acid for evaluating analgesic activity and the disk-diffusion method for testing antimicrobial actions. The results obtained demonstrated significant topical antiinflammatory and analgesic activities for the ethanol extract and chloroform fraction, but no relevant antimicrobial activity against the microorganisms tested. Copyright © 2002 John Wiley & Sons, Ltd. [source] Neonatal nociceptive somatic stimulation differentially modifies the activity of spinal neurons in rats and results in altered somatic and visceral sensationTHE JOURNAL OF PHYSIOLOGY, Issue 3 2006Adrian Miranda The role of intramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague,Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naďve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10,80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13,L1) were performed in adult pH 4.0 injected and naďve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions , 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 ± 2.2 impulses s,1), but not SL-A neurons (5.3 ± 0.9 impulses s,1) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 ± 0.8 impulses s,1; SL-A, 3.1 ± 0.7 impulses s,1). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures , 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation. [source] Biomechanics of the Fractured Medial Coronoid Process and the Isolated Anconeal Process in the Canine Elbow JointANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005J. Maierl Introduction:, Elbow dysplasia is one of the most important orthopaedic diseases of the canine elbow joint. The medial coronoid process (MCP) and the anconeal process (AP) are involved with a high incidence. Aims:, The aim of this study was to clarify whether these processes are especially loaded resulting in osteoarthrosis. Material and Methods:, Elbow joints were examined from dogs of various breeds, with a body weight over 20 kg and an age ranging from 1 to 12 years. Only joints without damage to the articular cartilage have been included in this investigation. Articular surfaces have been evaluated macroscopically, subchondral bone density (long-term loading) and split-lines (long-term tensile loading) have been determined. Results:, In the humeral fossa olecrani, there was a distinct impression on the inner side of the lateral compared to the medial epicondyle. In the ulna, the MCP was much greater than the lateral coronoid indicating that the medial process has to support the humeral condyle to a higher extent. Subchondral split lines with a transverse orientation in the fossa olecrani gave evidence of long-term transverse tensile loading in this area. Split lines on the MCP were oriented radially as if the lateral edge was bent downwards. Subchondral bone density in the fossa olecrani was higher towards the lateral epicondyle in comparison to the medial. Furthermore, there was a bone density maximum on the medial part of the humeral condyle opposite of the MCP with its very high density. Discussion:, Gait analyses showed that there is a transverse, medially oriented force of up to 4% bodyweight acting on the paw during midstance. As the carpus is stable when slightly hyperextended during midstance loading there is a long lever arm from the ground up to an assumed rotation centre in the depth of the trochlear notch. The medially directed ground reaction force slightly rotates the forearm inwards causing a bending moment about the elbow joint, which leads to an increased pressure of the AP and the MCP. This bending in addition to sagittal loading is the reason for the high susceptibility of the MCP and AP. [source] C-peptide prevents nociceptive sensory neuropathy in type 1 diabetesANNALS OF NEUROLOGY, Issue 6 2004Hideki Kamiya MD We examined the effects of C-peptide replacement on unmyelinated fiber function in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins, and the expression of neurotrophic receptors and content of neuropeptides in dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from onset of diabetes had no effect on hyperglycemia, but it significantly prevented progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and loss. These findings were associated with preventive effects on impaired availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and significant prevention of perturbed expression of insulin, insulin growth factor,1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion cells. These beneficial effects translated into prevention of the decreased content of dorsal root ganglia nociceptive peptides such as substance P and calcitonin gene,related peptide. From these findings we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions. Ann Neurol 2004 [source] Attenuation of pain and inflammation in adjuvant-induced arthritis by the proteasome inhibitor MG132ARTHRITIS & RHEUMATISM, Issue 7 2010Aisha S. Ahmed Objective In rheumatoid arthritis (RA), pain and joint destruction are initiated and propagated by the production of proinflammatory mediators. Synthesis of these mediators is regulated by the transcription factor NF-,B, which is controlled by the ubiquitin proteasome system (UPS). The present study explored the effects of the proteasome inhibitor MG132 on inflammation, pain, joint destruction, and expression of sensory neuropeptides as markers of neuronal response in a rat model of arthritis. Methods Arthritis was induced in rats by injection of heat-killed Mycobacterium butyricum. Arthritis severity was scored, and nociception was evaluated by mechanical pressure applied to the hind paw. Joint destruction was assessed by radiologic and histologic analyses. NF-,B DNA-binding activity was analyzed by electromobility shift assay, and changes in the expression of the p50 NF-,B subunit and the proinflammatory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry. Results Arthritic rats treated with MG132 demonstrated a marked reduction in inflammation, pain, and joint destruction. The elevated DNA-binding activity of the NF-,B/p50 homodimer and p50, as well as the neuronal expression of SP and CGRP, observed in the ankle joints of arthritic rats were normalized after treatment with MG132. Conclusion In arthritic rats, inhibition of proteasome reduced the severity of arthritis and reversed the pain behavior associated with joint inflammation. These effects may be mediated through the inhibition of NF-,B activation and may possibly involve the peripheral nervous system. New generations of nontoxic proteasome inhibitors may represent a novel pharmacotherapy for RA. [source] META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 6 2010Veera Reddy Konda Objective The multikinase inhibitor META060 has been shown to inhibit NF-,B activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. Methods Glycogen synthase kinase 3, (GSK3,),dependent ,-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1, (IL-1,),mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. Results META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and GSK3) associated with RA and inhibited ,-catenin phosphorylation. META060 inhibited osteoclastogenesis, as indicated by decreased transformation of RAW 264.7 cells to osteoclasts and reduced TRAP activity, and inhibited IL-1,,activated prostaglandin E2, matrix metalloproteinase 3, IL-6, IL-8, and monocyte chemotactic protein 1 in RASFs. In mice with acute inflammation, oral administration of META060 reduced paw swelling similar to the effect of aspirin. In mice with CIA, META060 significantly reduced the arthritis index and decreased bone, joint, and cartilage degradation. Serum IL-6 concentrations in these mice were inhibited in a dose-dependent manner. Conclusion Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases. [source] | |||||||||||||||||||||||||||||||||||||