Apoptosis of Biliary Epithelial Cells
Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso in The Pathophysiology of Biliary Epithelia, 2020
Cyclooxygenase-2 (Cox-2) is also induced by many of the proinflammatory cytokines produced by inflammatory and even epithelial cells during chronic inflammation. Overexpression of Cox-2 has been reported in many malignant gastrointestinal tumors, including colon cancer, and inhibition of Cox-2 expression may halt the development of malignancies. Recently, it has demonstrated that cytokines induce expression of Cox-2 in human cholangiocarcinoma cells, and this, in turn, attenuates Fas-induced apoptosis. Cox-2 cytoprotection or disruption of the homeostatic mechanism appears to be mediated by prostaglandin E2; a product of Cox-2 catalytic activity, which increases the expression of the antiapoptotic protein Mcl-1. Mcl-1 bloclcs the mitochondrial pathway of apoptosis.27 Interestingly, Cox-2 did not modulate TNF-α mediated apoptosis and only minimally suppressed TRAIL-induced apoptosis, suggesting intrinsic differences in the death-receptor pathways of apoptosis in malignant cholangiocytes.
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White in Advances in Spinal Fusion, 2003
Recently, the development of drugs that selectively inhibit the cyclooxygenase-2 enzyme has significantly changed the way in which NSAIDS are prescribed. These COX-2 inhibitors have been shown to have significantly fewer side effects than the nonselective NSAIDS, especially in regards to gastrointestinal bleeding. Much interest has also arisen as to the possibility of using these COX-2 inhibitors after spinal fusion. It has been shown that perioperative use of celecoxib or rofecoxib can significantly reduce pain and opioid use in patients undergoing spinal fusion. This same study also demonstrated that these medicines do not have to be discontinued preoperatively and that their use did not increase the risk of intraoperative bleeding [32]. In addition, a study by Lewis et al. [33] indicated that postoperative use of COX-2 inhibitors did not lead to an increased number of pseudarthroses. They found that the fusion rate in rats at 8 weeks after posterolateral spinal fusion was not statistically different in those rats receiving celecoxib versus the control group. They did, however, find a statistically significantly higher rate of nonunion (50%) in those rats who received indomethacin postoperatively. Although these early results with COX-2 inhibitors after spinal fusion are encouraging, there needs to be more research with human studies before stating their definite safety.
Epidemiology of Colorectal Cancer
Jim Cassidy, Patrick Johnston, Eric Van Cutsem in Colorectal Cancer, 2006
As regards other types of nonsteroidal anti-inflammatory drugs (NSAIDs), three small randomized clinical trials have shown that sulindac reduces the number and size of colorectal polyps in patients with FAP, confirming the results of studies of nonrandomized case series (88–106). However, in one trial in patients who were genotypically affected with FAP but were phenotypically unaffected, sulindac did not prevent the development of colorectal adenomas (107). In a small randomized trial, no regression of small adenomatous polyps in patients without FAP was observed (108). Celecoxib and rofecoxib specifically inhibit cyclooxygenase-2 (COX-2). Celecoxib has been found to reduce the number of colorectal adenomas in patients with FAP (109). In an analysis of data from a prescription drug database in the elderly in Québec (Canada), there was an inverse association between colorectal adenomas and use of rofecoxib for a period of at least 90 days (110). In a secondary analysis relating to colorectal cancer, there were inverse associations with use of rofecoxib and celecoxib.
Experimental in vivo model to evaluate the impact of Cernitin™ on pain response on induced chronic bladder inflammation
Published in Scandinavian Journal of Urology, 2022
Céline Augé, Nishtman Dizeyi, Lena Ramnemark, Philippe Lluel, Magnus Grabe
Cyclophosphamide-induced BPS in rodents is a well-characterized model [11–13]. Systemic CYP is metabolized in the liver but eliminated primarily through the kidneys. CYP’s major uro-toxic metabolite is acrolein, which causes mucosal inflammation as indicated by microscopic changes in the bladder and the presence of inflammatory cell infiltrations as well as visceral pain [2,14]. This experimental model makes CYP-induced BPS the optimal choice to elucidate mechanisms, identify specific biomarkers related to this chronic condition and subsequently finding effective therapeutic options. A chronic condition, inducing inflammation and tissue damage, can change the properties of sensory pathways leading to a reduction in pain threshold (allodynia) and an amplification of painful sensations (hyperalgesia) [2]. Furthermore, chronic CYP-induced BPS may involve alterations in neurotrophic factors, chemokines [12,15] and cytokines [16]. The presence of pro-inflammatory cytokines can induce cyclooxygenase-2 (COX-2) enzyme, an inflammatory early response gene [17] and generate prostaglandins, a substance that plays a role in the inflammation process. In this study, we hypothesize that CYP-induced BPS upregulates COX-2 [18] and prostanoids [19] in the urinary bladder, which contributes to altered urodynamic function. Cyclooxygenase-2 has also been reported to have a nociceptive (analgesic) effect in both the central and peripheral nervous systems. They show the improvement in bladder function with administration of a specific COX-2 inhibitor [20] suggesting the pivotal role of COX-2 and prostanoids in BPS.
Multimodal analgesia in neurosurgery: a narrative review
Published in Postgraduate Medicine, 2022
Caterina Aurilio, Maria Caterina Pace, Pasquale Sansone, Luca Gregorio Giaccari, Francesco Coppolino, Vincenzo Pota, Manlio Barbarisi
It is now understood that there are two forms of cyclooxygenase, termed cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is a constitutive isoform found in normal tissues, while COX-2 is induced in settings of inflammation and is constitutively expressed in certain areas of brain. NSAIDs are usually classified as mild analgesics, but it is important to consider the type of pain and its intensity in the assessment of analgesic efficacy. In postoperative pain, the NSAIDs may be superior to the opioids because they are particularly effective in different contests in which inflammation has caused sensitization of pain receptors [16]. The inhibition of COX-1 correlates with the inhibition of endogenous prostaglandins that impairs platelet function and promotes the ability of these drugs to increase the perioperative bleeding time. Probably for this reason, there are few clinical studies on the use of NSAIDs in brain surgery. In a Cochrane review, six studies were included in a meta-analysis on 742 patients to assess acute postoperative intensity of pain in brain surgery [10,17,18].
Preparation of celecoxib tablet by hot melt extrusion technology and application of process analysis technology to discriminate solubilization effect
Published in Pharmaceutical Development and Technology, 2020
Ilhwan Hwang, Vanamane Renuka, Ju-Hyun Lee, Kwon-Yeon Weon, Chin-Yang Kang, Beom-Jin Lee, Jun-Bom Park
Celecoxib is a nonsteroidal anti-inflammatory drug with high selectivity for cyclooxygenase 2. Celecoxib has fewer gastrointestinal adverse effects, and thus is widely used to treat various conditions, including toothache, rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis. Its melting point is 158 °C and water solubility is 3.3 mg/L, showing very low solubility in water (Morgen et al. 2012). Thus, celecoxib is considered as a BCS Class II drug, which is poorly water-soluble with low bioavailability (Paradkar et al. 2003; Fong et al. 2016). Currently, numerous studies on the solubilization of poorly water-soluble drugs are underway. Proposed solubilization methods include the preparation of salts, water-soluble prodrugs, use of surfactants, or formation of solid dispersions (SDs; Vasconcelos et al. 2007; Huang and Dai 2014).
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