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Glutamate and MDMA Neurobehavioral ToxicityAnneken, John H. January 2012 (has links)
No description available.
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The Role of Cyclooxygenase-2 in Newborn Hyperoxic Lung InjuryBritt, Rodney Deon, Jr. 17 December 2012 (has links)
No description available.
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The Effects of Epidural Deracoxib on the Ground Reaction Forces in an Acute Stifle Synovitis ModelKarnik, Priti S. 13 June 2005 (has links)
Objective: To evaluate epidurally administered deracoxib and its ability to mediate clinical signs and effects of a sodium urate crystal-induced stifle synovitis in dogs, and to compare the effects of epidural versus subcutaneously injected deracoxib.
Study Design: Experimental, randomized, double-blinded, placebo controlled modified cross over design.
Animals or Study Population: 24 random source adult mixed breed dogs, 14 males and 10 females.
Methods: Sodium urate crystals were used to create a stifle synovitis model to evaluate the effectiveness of administered deracoxib. Dogs were divided into four treatment groups; 3 mg/kg epidural deracoxib, 1.5 mg/kg epidural deracoxib, 3 mg/kg subcutaneous deracoxib and a placebo group (the vehicle for deracoxib was used). Force plate and subjective evaluations were performed at Time 0, 2, 4, 8, 12, and 24 hours post treatment. A repeated measures ANOVA with Bonferroni-corrected post-hoc comparisons was used to determine treatment effects.
Results: Overall, peak vertical force (PVF) and vertical impulse (VI) were both significantly higher in all deracoxib treated dogs compared to placebo. Both 3 mg/kg epidural and subcutaneous deracoxib had significantly higher PVF and VI than 1.5 mg/kg epidural deracoxib. The overall pain score for all deracoxib treated dogs was significantly lower than the placebo treated dogs.
Conclusions: Epidural deracoxib is effective at providing analgesia in an acute pain model, but it does not appear to be more effective than systemic administration.
Clinical Relevance: The use of injectable deracoxib is effective in providing analgesia in acute inflammatory conditions of the stifle joint in dogs. / Master of Science
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Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy : effects of nimesulideGu, Baoying. January 2007 (has links)
Wernicke's encephalopathy is a neuropsychiatric disorder resulting from thiamine deficiency (TD) and is characterized by neuronal loss, astrocytic proliferation and microglial activation. Cyclooxygenases (COX) are enzymes which catalyze the first step in the synthesis of prostanoids. COX-1 is expressed constitutively and COX-2 is the inducible isoform. Groups of TD rats and pair-fed controls were killed at presymptomatic and symptomatic stages of encephalopathy. Cresyl violet and NeuN staining showed decreased numbers of neuronal cells in vulnerable regions (medial thalamus and inferior colliculus) but not in a spared region (frontal cortex). Numbers of GFAP-positive and OX-42-positive cells were increased at symptomatic stage of encephalopathy. Expression of COX-2 mRNA and neuronal COX-2 immunoreactivity were selectively increased in vulnerable regions of TD rats at symptomatic stages of encephalopathy. Nimesulide, a highly selective COX-2 inhibitor, lowered PGE2 levels and precipitated the progression of encephalopathy suggesting that COX-2 in this model is conferring neuroprotection.
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Lipid mediators in the development and resolution of experimental lyme arthritisBlaho, Victoria Alison. January 2007 (has links)
Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2007" Includes bibliographical references.
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Selektive COX-2 Inhibitoren und Nierenschädigung bei salzsensitiver Hypertonie /Bühler, Nico Martin. January 2009 (has links)
Diss. med. dent. Zürich. / Literaturverz.
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Selektive COX-2 Inhibitoren und Nierenschädigung bei salzsensitiver Hypertonie /Bühler, Nico Martin. January 2009 (has links)
Diss. med. dent. Zürich. / Literaturverz.
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Propriétés anti-inflammatoires des statines, des triterpénoïdes et des dérivés de thiazole : rôle de la hème-oxygénase-1 et de la cyclooxygénase-2 / Anti-inflammatory properties of statins, triterpenoids and thiazole derivatives : role of heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2)Ghewa, El Achkar 05 November 2015 (has links)
Les statines sont des inhibiteurs sélectifs de la 3-hydroxy-3-méthylglutaryl-coenzyme A réductase, utilisées pour diminuer la biosynthèse du cholestérol. Ces molécules possèdent en plus de leur capacité à réduire le cholestérol des effets pléiotropiques comme les propriétés anti-inflammatoires et anti-oxydantes. Les cucurbitacines sont des triterpènes dérivés des plantes, ayant des propriétés biologiques diverses comme les effets anti-inflammatoires et anticancéreux, associées toutefois à une toxicité élevée. Les dérivés de thiazole sont des molécules contenant un noyau hétérocyclique formé de trois atomes de carbones, un atome de sulfure et un atome d'azote, disposant des effets anti-inflammatoires importantes. Les cyclooxygénases et les hème-oxygénases jouent un rôle dans l'inflammation et le stress oxydatif et sont les cibles des statines et des cucurbitacines in vitro. Les dérivés de thiazole peuvent inhiber plutôt l'activité enzymatique des cyclooxygénases. Le but de ma thèse est d'étudier les effets de ces 3 molécules in vivo et d'analyser si possible les mécanismes impliqués, comme par exemple pour les statines. Pour cela, nous avons eu recours chez les souris C57BL/6 au modèle d'inflammation de la poche à air-stérile injecté par le zymosan.Nous avons d'abord montré que le traitement des souris avec l'atorvastatine pendant 10 jours a réduit la migration des cellules dans l'exsudat de la poche à air ainsi que l'expression de gènes des marqueurs pro-inflammatoires tels que les cytokines, les chimiokines, la cyclooxygénase-2 et la nitric oxide synthase -II. Le taux de la prostaglandine E2 et de l'interleukine-6 a été également réduit. L'inhibition de l'hème-oxygénase-1 par son inhibiteur sélectif, tin protoporphyrine, a partiellement réduit l'effet inhibiteur de l'atorvastatine sur la migration des cellules et sur certaines cytokines suggérant un rôle important de la l'hème-oxygénase-1 dans les propriétés anti-inflammatoires in vivo.En parallèle, nous avons utilisé ce modèle animal tester l'effet de la cucurbitacine E sur l'inflammation et évaluer le rôle d'encapsulation in vivo dans des liposomes à base de phosphatidylcholine. Nous avons démontré que la cucurbitacine E libre (12.5 μg/poche ou 25 μg/poche) a tendance à diminuer l'interleukine-6, l'hème oxygénase-1 et la cyclooxygénase-2 alors que la cucurbitacine E encapsulée (12.5 μg/poche) a significativement réduit la prostaglandine E2, l'interleukine-6 et le taux de nitrite sans affecter le niveau d'ARNm de la cyclooxygénase-2 et l'hème oxygénase-1. Nos résultats suggèrent que l'incorporation de la cucurbitacine E dans des liposomes améliore son effet anti-inflammatoire et réduit sa cytotoxicité.Finalement, deux dérivés de thiazole qui diffèrent dans leur structure par la présence d'un groupement butyle- ou benzyle- sur leur chaîne latérale, ont été explorés dans ce modèle. Nous avons montré que le dérivé de thiazole contenant le groupe benzyle est sélectif de la cyclooxygénase-2 dans les macrophages et le modèle in vivo chez la souris.En résumé, mon travail de thèse met en évidence in vivo les effets anti-inflammatoires des statines et le rôle de l'hème oxygénase-1, et permet en plus la caractérisation des effets anti-inflammatoires des cucurbitacines et des dérivés de thiazole. L'ensemble de ces résultats renforcent les effets anti-inflammatoires de ces substances et démontre in vivo leur effet et les suggèrent comme molécules anti-inflammatoires. / Statins are selective competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase used to lower cholesterol biosynthesis and have multiple pleiotropic effects beyond lowering cholesterol such as anti-inflammatory and anti-oxidant properties. Cucurbitacins are triterpenoid derived from plants and exhibit potential anti-inflammatory and anticancer properties though they have a high cytotoxicity. Thiazole derivatives are molecules containing heterocyclic ring with three carbons, one sulfur and one nitrogen atom, with important anti-inflammatory activities. Cyclooxygenases and heme-oxygenases play a role in inflammation and oxidative stress and are targets for statins or cucurbitacins in vitro. Thiazole derivatives are potential inhibitors of cyclooxygenases. The aim of my thesis is to investigate the anti-inflammatory effect of these three compounds in vivo and attempt to analyze the mechanisms involved, mainly for statins. Thus we set up an animal model of inflammation in C57BL/6 corresponding to the zymosan -injected dorsal sterile air pouch.First we have shown that treatment of mice with atorvastatin for 10 days reduced cell migration in the exudate of the air pouch as well as the expression of inflammatory markers such as cytokines, chemokines, cyclooxygenase-2 and nitric oxide synthase -II. The synthesis of prostaglandin E2 and interleukin-6 was also reduced. Inhibition of heme-oxygenase-1 by the selective inhibitor tin protoporphyrin partially diminished the inhibitory effect of statins on cell migration and some cytokines suggesting a significant role of HO-1 in the anti-inflammatory properties for atorvastatin in vivo.For cucurbitacins, we used the same animal model to investigate the effect of this substance in vivo and further assess the beneficial effect of encapsulating cucurbitacin in phosphatidylcholine-liposomes. Free cucurbitacin E (12.5 μg/pouch or 25 μg/pouch) tended to increase interleukin-6, decrease heme oxygenase-1 and cyclooxygenase-2 whereas cucurbitacin E loaded liposomes (12.5 μg/pouch) significantly reduced prostaglandin E2, interleukin-6 and nitrite without affecting cyclooxygenase-2 and heme oxygenase-1 mRNA levels. We demonstrated that the incorporation of Cuc E into liposomes enhances its anti-inflammatory effect and reduces its cytotoxicity.Finally, we used the dorsal air pouch model to investigate the anti-inflammatory effect of two thiazole derivatives that differ in their side chain by the presence of butyl or benzyl group. In addition to analyzing their effect on cyclooxygenase activity in human blood platelets, on recombinant COX-1 and in culture macrophage cell lines, we demonstrated their capacity to block cyclooxygenase-dependent prostaglandin synthesis in the lumen of the air pouch.In summary, my thesis presents in vivo evidence for the anti-inflammatory effects of atorvastatin dependent on HO-1 activity. My studies characterized the anti-inflammatory effects of cucurbitacins and thiazole derivatives. All these results support the anti-inflammatory effects of these substances and suggested them as potential anti-inflammatory substances.
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Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy : effects of nimesulideGu, Baoying. January 2007 (has links)
No description available.
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Regulation of Cyclooxygenase-2 by Environmental and Dietary FactorsDegner, Stephanie C January 2007 (has links)
Each year over 260,000 new cases of breast cancer will be diagnosed in the U.S. and approximately 40,000 women will die of metastatic breast cancer. The etiology of breast cancer is poorly understood and only 5 -10% of cases can be attributed to genetic factors. This suggests that the development of breast cancer may involve environmental factors including diet, lifestyle, and exposure to chemicals. Several lines of experimental and epidemiological evidence have highlighted COX-2 as a potential target for breast cancer prevention. The central hypothesis of this proposal is that activation of COX-2 transcription by epigenetic effectors can be prevented by dietary agents that target the activator protein-1 (AP-1) transcription factor and the aromatic hydrocarbon receptor (AhR). The first specific aim was to determine the mechanism through which conjugated linoleic acid (CLA) and rosmarinic acid (RA) inhibit TPA-induced COX-2 trancription. These studies documented that CLA and RA repressed COX-2 transcription by antagonizing the AP-1 transcription factor. The second specific aim was to investigate whether or not the AhR plays a role in TCDD-induced COX-2 transcription and effects of chemopreventive agents. Results indicated that AhR agonists induced the binding of the AhR to COX-2 and was prevented by CLA and the AhR antagonist, resveratrol (RES) and 3-methoxy-4-nitroflavone (3M4NF). The third specific aim was to examine the effects of AhR agonists and dietary selective AhR modulators on chromatin modifications associated with the COX-2 promoter. Chromatin immunoprecipitation (ChIP) assays revealed that the AhR is recruited to the region of the COX-2 promoter containing a xenobiotic response element and accompanied by recruitment of p300 and acetylation of histone H4. Transcriptional regulation of COX-2 by AhR agonists and dietary antagonists may also involve other post-transcriptional modifications of histones, which along with chromatin remodeling factors modulate the structure of chromatin and recruitment of RNA polymerase II. Overall, the results demonstrated that COX-2 transcription can be targeted by a variety of dietary agents that act through different mechanisms. Therefore, inhibition of transcriptional regulation of COX-2 by selected dietary factors may be a breast cancer preventive strategy that bypasses the side effects of drugs that target COX-2.
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