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Arachidonic Acid Metabolites (arachidonic + acid_metabolite)
Selected AbstractsRole of systemic and local administration of selective inhibitors of cyclo-oxygenase 1 and 2 in an experimental model of periodontal disease in ratsJOURNAL OF PERIODONTAL RESEARCH, Issue 2 2009C. M. Queiroz-Junior Background and Objective:, Periodontal disease is an inflammatory condition of tooth-supporting tissues. Arachidonic acid metabolites have been implicated in development of periodontal disease, especially those derived from the cyclo-oxygenase (COX) pathway. This study investigated the role of inhibitors of cyclo-oxygenases (COX-1 and COX-2) in a model of periodontal disease in rats. Material and Methods:, A ligature was placed around the molar of rats. Losses of fiber attachment and of alveolar bone were measured morphometrically in histologically prepared sections. Infiltration of cells into gingival tissue surrounding the ligated tooth was also determined. Results:, Systemic and local administration of non-selective and selective COX-2 inhibitors, preventively, resulted in significant reduction of the losses of fiber attachment and alveolar bone, as well as decreased leukocyte numbers in gingival tissue. Preventive selective inhibition of COX-1 was as effective as COX-2 inhibition in reducing local fiber attachment loss and cell migration, but did not prevent alveolar bone loss. Conclusion:, Our results provide evidence for participation of COX-1 and COX-2 in early stages of periodontal disease in rats. Furthermore, local administration of COX inhibitors reduced the signs of periodontal disease to the same extent as systemic treatment. Therapeutic approaches incorporating locally delivered anti-inflammatory drugs could be of benefit for patients suffering from periodontal disease. [source] Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute maniaBIPOLAR DISORDERS, Issue 7 2007M Elizabeth Sublette Objectives:, Nutritionally essential polyunsaturated fatty acids (PUFAs) have been implicated as potentially important factors in mood disorders. For instance, n-3 PUFA supplementation is reported to improve outcomes in major depressive disorder and bipolar disorder. However, the role of PUFAs in acute mania has been minimally investigated. We performed a pilot study to compare plasma levels of free (non-esterified) and esterified PUFAs between patients in an acute manic episode and healthy volunteers, and to explore associations between symptom severity and levels of fatty acids and of the arachidonic acid metabolite, prostaglandin E2 (PGE2). Methods:, Patients (n = 10) who were medication-free for at least two weeks and seeking inpatient admission for an acute manic episode were compared with healthy volunteers (n = 10). Symptom severity was assessed at admission and after six weeks of naturalistic treatment. Fasting baseline free and esterified plasma levels of docosahexaneoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3), arachidonic acid (AA,20:4n-6) and the AA metabolite PGE2 were determined, and PGE2 levels were tested again at six weeks. Results:, No between-group differences were found in levels of individual or total fatty acids, or of PGE2. Among subjects, manic symptom severity correlated negatively with levels of free AA and free EPA, and positively with the free AA:EPA ratio. PGE2 levels did not differ between groups or in subjects pre- and post-treatment. Conclusions:, Our preliminary results suggest that, in susceptible persons, low plasma levels of free EPA compared with AA are related to the severity of mania. [source] A link between endoplasmic reticulum stress-induced , -cell apoptosis and the group VIA Ca2+ -independent phospholipase A2 (iPLA2,)DIABETES OBESITY & METABOLISM, Issue 2010X. Lei Endoplasmic reticulum (ER) stress is becoming recognized as an important contributing factor in various diseases, including diabetes mellitus. Prolonged ER stress can cause , -cell apoptosis; however, the underlying mechanism(s) that contribute to this process are not well understood. Early reports suggested that arachidonic acid metabolites and a Ca2+ -independent phospholipase A2 (iPLA2) activity play a role in , -cell apoptosis. The PLA2 family of enzymes catalyse the hydrolysis of the sn -2 substituent (i.e. arachidonic acid) of membrane phospholipids. In light of our findings that the pancreatic islet , -cells are enriched in arachidonate-containing phospholipids and express the group VIA iPLA2,, we considered the possibility that iPLA2, participates in ER stress-induced , -cell apoptosis. Our work revealed a novel mechanism, involving ceramide generation and triggering of mitochondrial abnormalities, by which iPLA2, participates in the , -cell apoptosis process. Here, we review our evidence linking ER stress, , -cell apoptosis and iPLA2,. Continued studies in this area will increase our understanding of the contribution of iPLA2, to the evolution of diabetes mellitus and will further our knowledge of factors that influence , -cell health in diabetes mellitus and identify potential targets for future therapeutic interventions to prevent , -cell death. [source] The 8-epimer of prostaglandin F2,, a marker of lipid peroxidation and oxidative stress, is decreased in the nipple aspirate fluid of women with breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Ferdinando Mannello Abstract Breast cancer (BC), a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. Whether lipid peroxidation in the mammary gland promotes or prevents tumorigenesis is unclear. Malondialdehyde (MDA) and the 8-epimer of Prostaglandin F2, (8-iso-PGF2,), two lipid peroxidation markers, were studied in milk (n = 10), NAF (n = 140) and plasma (n = 35) samples. MDA was detected in all plasma, in 80% of milk samples and in 95% of NAF samples. MDA levels in NAF and plasma were significantly higher than in milk (p = 0.016 and p = 0.029, respectively). We found no significant difference between levels of MDA in NAF samples from BC patients compared to healthy controls. 8-iso-PGF2, was detectable in all samples. 8-iso-PGF2, median levels in NAF were significantly higher than in both milk and plasma (p < 0.0001). The highest 8-iso-PGF2, levels were found in NAF from healthy women, significantly higher than in women with BC (p < 0.0001). No significant differences were found in both markers after the age-adjustment. High levels of lipid peroxidation products in NAF suggest their in situ production in the nonlactating breast. Active lipid peroxidation may have a physiologic role in the normal mammary gland. Lower levels of 8-iso-PGF2, in NAF from BC patients suggest altered production of arachidonic acid metabolites during breast carcinogenesis. © 2006 Wiley-Liss, Inc. [source] Efficient Synthesis of Either Enantiomer of Ethyl 5-Hydroxyhept-6-enoateADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 8-9 2007Thomas Fischer Abstract The application of alcohol dehydrogenases as a key-step for the synthesis of the title compound is reported. 5-Hydroxyhept-6-enoates are versatile intermediates, e.g., for the synthesis of a variety of arachidonic acid metabolites. [source] Local application of n,3 or n,6 polyunsaturated fatty acids in the treatment of human experimental gingivitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002Jörg Eberhard Abstract Background: Polyunsaturated fatty acids have the potential to attenuate inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which show opposite effects to the pro-inflammatory arachidonic acid metabolites such as leukotriene B4 (LTB4). Aims: The aim of this clinical study was to evaluate the effects of topical application of n,6 or n,6 polyunsaturated fatty acids in patients with experimental gingivitis. Methods: In each subject, similar teeth served as experimental and control over a 21-day non-hygiene phase and a 9-day resolving phase. Efficacy assessment was based on the bleeding on probing frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined by inserting a filter paper strip for 30 s and measurements were performed on a Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high-pressure liquid chromatography. Results: After 21 days of plaque growth, the BOP, GCF and LTB4 levels were significantly increased in all groups, with no differences between the control and experimental side. Rinsing of an area with established gingivitis for a 9-day period significantly reduced the GCF in the n,6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile range)). Conclusion: The topical application of n,6 or n,6 fatty acids failed to inhibit the development of experimental gingivitis. Rinsing with n,6 fatty acids could reduce the level of GCF in established experimental gingivitis. Zusammenfassung Hintergrund: Vielfach ungesättigte Fettsäuren haben das Potential, die Entzündung durch die Synthese von Mediatoren des 15-Lipoxygenaseweges zu behindern. Dies zeigt Gegeneffekte zu den pro-inflammatorischen Arachnoidonsäuremetaboliten wie Leukotrien B4 (LTB4). Ziele: Das Ziel dieser klinischen Studie war die Überprüfung des Effektes einer topischen Applikation von n,3 oder n,6 vielfach ungesättigten Fettsäuren bie Patienten mit experimenteller Gingivitis. Methoden: Bei jeder Person dienten ähnliche Zähne als Experiment und Kontrollen über eine 21tägige Nichthygiene-Phase und einer 9tägigen Erholungsphase. Wirksamkeitsmessungen basierten auf der Häufigkeit von Provokationsblutung (BOP) und dem Volumen der gingivalen krevikulären Flüssigkeit (GCF). GCF wurde durch Einbringen von Filterpapierstreifen für 30 Sekunden bestimmt. Die Messungen wurden mit einen Periotron 8000 durchgeführt. Die LTB4 Konzentration wurde mit der Umkehrphasen-Hochdruck-Flüssigkeitschromatographie analysiert. Ergebnisse: Nach 21 Tagen des Plaquewachstums waren die Level für BOP, GCF und LTB4 in allen Gruppen signifikant erhöht, ohne Differenzen zwischen den Kontrollen und den experimentellen Flächen. Die Spülung eines Gebietes mit etablierter Gingivitis für eine 9tägige Periode reduzierte die GCF in der n,6 Gruppe signifikant (71.9 (18.7) versus 47.4 (11.4) Peritron-Einheiten, Median (Zwischenquartilstreuung)). Zusammenfassung: Die topische Applikation von n,3 oder n,6 Fettsäuren verhindert die Entwicklung einer experimentellen Gingivitis nicht. Die Spülung mit n,6 Fettsäure konnte den Level der GCF bei einer bestehenden experimentellen Gingivitis reduzieren. Résumé Origine: Les acides gras poly-insaturés ont le potentiel d'atténuer l'inflammation en synthétisant des médiateurs des voies de la lipoxygénase 15 qui montrent des effets opposés aux métabolites de l'acide arachidonique pro-inflammatoire comme la leucotriène B4 (LTB4). But: Le but de cette étude clinique a été d'évaluer les effets de l'application topique d'acide gras poly-insaturés n,3 ou n,6 chez des patients effectuant d'une gingivite expérimentale. Méthodes: Chez chaque sujet, des dents semblables ont servi de sites tests et contrôles durant une phase sans hygiène buccale de 21 jours et une phase de retour à la normale de 9 jours. L'efficacité a été mesurée sur base de la fréquence du saignement au sondage (BOP) et le volume de fluide gingivale (GCF). Le GCF a été déterminé en insérant des papiers filtres pendant 30 s et les mesures ont été lues à l'aide du Périotron 8000. La concentration de LTB4 a été analysée par chromotographie liquide à haute pression à phrase arrière. Résultats: Après 21 jours d'accumulation de plaque dentaire les niveaux de BOP, GCF et LTB4 ont augmenté significativement dans tous les groupes sans aucune différence entre les sites tests et contrôles. Le rinçage d'une zone avec gingivite établie durant une période de 9 journées diminuait les GCF dans le groupe n,6 (unités du Péritron 72 (médian 19) versus 47 (11)). Conclusion: L'application topique d'acide gras n,3 ou n,6 ne permettait pas d'inhiber le développement de la gingivite expérimentale. Le rinçage avec des acides gras n,6 pouvait réduire le niveau de GCF dans la gingivite expérimentale établie. [source] A phosphatidylinositol transfer protein ,-dependent survival factor protects cultured primary neurons against serum deprivation-induced cell deathJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Hanneke Bunte Abstract Selective neuronal loss is a prominent feature in both acute and chronic neurological disorders. Recently, a link between neurodegeneration and a deficiency in the lipid transport protein phosphatidylinositol transfer protein , (PI-TP,) has been demonstrated. In this context it may be of importance that fibroblasts overexpressing PI-TP, are known to produce and secrete bioactive survival factors that protect fibroblasts against UV-induced apoptosis. In the present study it was investigated whether the conditioned medium of cells overexpressing PI-TP, (CM,) has neuroprotective effects on primary neurons in culture. We show that CM, is capable of protecting primary, spinal cord-derived motor neurons from serum deprivation-induced cell death. Since the conditioned medium of wild-type cells was much less effective, we infer that the neuroprotective effect of CM, is linked (in part) to the PI-TP,-dependent production of arachidonic acid metabolites. The neuroprotective activity of CM, is partly inhibited by suramin, a broad-spectrum antagonist of G-protein coupled receptors. Western blot analysis shows that brain cortex and spinal cord express relatively high levels of PI-TP,, suggesting that the survival factor may be produced in neuronal tissue. We propose that the bioactive survival factor is implicated in neuronal survival. If so, PI-TP, could be a promising target to be evaluated in studies on the prevention and treatment of neurological disorders. [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] Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channelsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001J Grainger The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. In endothelium-intact rings precontracted to the thromboxane A2 mimetic, U46619, anandamide (0.01 , 30 ,M) induced slowly developing concentration-dependent relaxations (pEC50 [negative log of EC50]=6.1±0.1; Rmax [maximum response]=81±4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying Rmax. Methanandamide was without effect on U46619-induced tone. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 ,M), the vanilloid receptor antagonist, capsazepine (3 and 10 ,M) or the nitric oxide synthase inhibitor, L -NAME (100 ,M). The cyclo-oxygenase inhibitor, indomethacin (3 and 10 ,M) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 ,M), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 ,M), shifted the anandamide concentration-response curve to the right. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (Rmax=7±7%), as did K+ channel blockade with tetraethylammonium (TEA; 3 ,M) or iberiotoxin (100 nM). Blockade of small conductance, Ca2+ -activated K+ channels, delayed rectifier K+ channels, KATP channels or inward rectifier K+ channels was without effect. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels. British Journal of Pharmacology (2001) 134, 1003,1012; doi:10.1038/sj.bjp.0704340 [source] The role of arachidonic acid metabolites in DRACTA OPHTHALMOLOGICA, Issue 2008AM ABU EL ASRAR Purpose The inducible enzyme cyclooxygense-2 (COX-2) and its metabolic products are important mediators for angiogenesis. We investigated the expression of COX-2 and its downstream enzymes microsomal prostaglandin-E synthase (mPGES)-1, cytosolic PGES (cPGES) and thromboxane synthase (TXS) and correlated it with vascular endothelial growth factor (VEGF) expression and level of vascularization in proliferative diabetic retinopathy (PDR) epiretinal membranes. Methods Fourteen membranes were studied by immunohistochemistry. Results Vascular endothelial cells expressed COX-2, mPGES-1 and VEGF in 75.6%, 64.3% and 50% of the membranes, respectively. TXS was expressed in stromal cells in 85.7% of the membranes. There was no immunoreactivity for cPGES. There were significant correlations between number of blood vessels expressing CD34 and the numbers of blood vessels expressing COX-2 (rs = 0.858; p<0.001), mPGES-1 (rs = 0.743; p = 0.002) and VEGF (rs = 0.845; p = 0.001) and the number of cells expressing TXS (rs = 0.74; p = 0.002). Number of blood vessels expressing VEGF correlated significantly with the numbers of blood vessels expressing COX-2 (rs = 0.879; p<0.001) and mPGES-1 (rs = 0.942; p<0.001) and the number of cells expressing TXS (rs = 0.702; p = 0.011). Conclusion COX-2 and its metabolic products might contribute to PDR angiogenesis. [source] | |||||||||||||||||||