المؤلفون: Eleni G. Andreadou, Georgios Katsipis, Magda Tsolaki, Anastasia A. Pantazaki

المصدر: Journal of Neuroimmunology. 357:577561

مصطلحات موضوعية: Lipopolysaccharides, Male, 0301 basic medicine, Immunology, Inflammation, Disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Blood serum, Bacterial Proteins, Alzheimer Disease, Humans, Immunology and Allergy, Medicine, Dementia, Cognitive Dysfunction, Cognitive impairment, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, carbohydrates (lipids), 030104 developmental biology, Neurology, Prostaglandin-Endoperoxide Synthases, Mental state, Female, lipids (amino acids, peptides, and proteins), Neurology (clinical), medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery

الوصف: This study reports elevated levels of bacterial lipopolysaccharides (LPSs) and cyclooxygenases (COX-1/2) in blood serum and cerebrospinal fluid (CSF) of Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) patients compared to cognitively healthy individuals, indicating LPSs as promising biomarkers, especially in serum. LPSs, in both fluids, positively correlate with COX-1/2, Αβ42 and tau and negatively with mental state. Furthermore, COX-2 is the main determinant of LPSs presence in serum, whereas COX-1 in CSF. These results underline the significance of microbial/ inflammatory involvement in dementia and offer novel perspectives on the roles of LPSs and COX in pathogenesis of AD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::190d565f66af422f91e5e8835fc5bc4eTest
https://doi.org/10.1016/j.jneuroim.2021.577561Test

المؤلفون: Subha Arthur, Uma Sundaram, Soudamani Singh

المصدر: Journal of Cellular and Molecular Medicine

مصطلحات موضوعية: Male, 0301 basic medicine, Leukotrienes, Indoles, Glutamine, Lipoxygenase, SN2/SNAT5, Crypt, Glutamine transport, Stimulation, Arachidonic Acids, Pharmacology, 03 medical and health sciences, 0302 clinical medicine, Ileum, Animals, Lipoxygenase Inhibitors, Enzyme Inhibitors, Arachidonyl trifluoromethyl ketone, Leukotriene, Arachidonic Acid, biology, Coccidiosis, Chemistry, Anti-Inflammatory Agents, Non-Steroidal, Sodium, Original Articles, Cell Biology, Enteritis, prostaglandins and crypt cells, 3. Good health, Amino Acid Transport Systems, Neutral, 030104 developmental biology, Gene Expression Regulation, Prostaglandin-Endoperoxide Synthases, Chronic Disease, biology.protein, Molecular Medicine, Eimeria, Original Article, 030211 gastroenterology & hepatology, Rabbits, Cyclooxygenase, Cotransporter

الوصف: The only Na‐nutrient cotransporter described in mammalian small intestinal crypt cells is SN2/SNAT5, which facilitates glutamine uptake. In a rabbit model of chronic intestinal inflammation, SN2 stimulation is secondary to an increase in affinity of the cotransporter for glutamine. However, the immune regulation of SN2 in the crypt cells during chronic intestinal inflammation is unknown. We sought to determine the mechanism of regulation of Na‐nutrient cotransporter SN2 by arachidonic acid metabolites in crypt cells. The small intestines of New Zealand white male rabbits were inflamed via inoculation with Eimeria magna oocytes. After 2‐week incubation, control and inflamed rabbits were subjected to intramuscular injections of arachidonyl trifluoromethyl ketone (ATK), piroxicam and MK886 for 48 hrs. After injections, the rabbits were euthanized and crypt cells from small intestines were harvested and used. Results: Treatment of rabbits with ATK prevented the release of AA and reversed stimulation of SN2. Inhibition of cyclooxygenase (COX) with piroxicam did not affect stimulation of SN2. However, inhibition of lipoxygenase (LOX) with MK886, thus reducing leukotriene formation during chronic enteritis, reversed the stimulation of SN2. Kinetic studies showed that the mechanism of restoration of SN2 by ATK or MK886 was secondary to the restoration of the affinity of the cotransporter for glutamine. For all treatment conditions, Western blot analysis revealed no change in SN2 protein levels. COX inhibition proved ineffective at reversing the stimulation of SN2. Thus, this study provides evidence that SN2 stimulation in crypt cells is mediated by the leukotriene pathway during chronic intestinal inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d3094ffb3273d2a6ff095ab1feaf6bfTest
https://doi.org/10.1111/jcmm.13257Test

المؤلفون: Nahid Ali, Shubhadeep Roychoudhury, Subhash C. Mandal, Dhrubojyoti Mukherjee, Asad, Partha Palit, Poulami Mahanta, Shadab

المصدر: Inflammopharmacology. 26:235-250

مصطلحات موضوعية: Male, 0301 basic medicine, Anti-Inflammatory Agents, Arthritis, Pharmacology, Plant Roots, Nociceptive Pain, law.invention, Mice, 0302 clinical medicine, Euphorbia, law, Edema, Medicine, Pharmacology (medical), Acetic Acid, Analgesics, biology, 030220 oncology & carcinogenesis, Neuropathic pain, Cytokines, Female, Steroids, Euphorbia tirucalli, medicine.drug_class, Immunology, Analgesic, Nitric Oxide, Anti-inflammatory, Proinflammatory cytokine, 03 medical and health sciences, Cell Line, Tumor, Animals, Inflammation, Plant Extracts, Terpenes, business.industry, biology.organism_classification, medicine.disease, Rats, RAW 264.7 Cells, 030104 developmental biology, Prostaglandin-Endoperoxide Synthases, biology.protein, Medicine, Traditional, Cyclooxygenase, Nitric Oxide Synthase, Phytotherapy, business

الوصف: The plant Euphorbia tirucalli Linn has been successfully used as a tribal folk medicine in India and Africa for the management of acute inflammatory, arthritic, nociceptive pain and asthmatic symptoms. The present study was conducted to assess the anti-inflammatory, analgesic, anti-asthmatic and anti-arthritic role of the total steroid and terpenoid rich fractions of the hydro-alcoholic extract of E. tirucalli root (STF-HAETR). STF-HAETR fraction demonstrated 71.25 ± 2.5 and 74.25 ± 5.1% protection against acetic acid-induced pain and central neuropathic pain at 75 and 100 mg/kg doses, respectively. It showed 96.97% protection against acute inflammation at 100 mg/kg with 1.6-fold better activity than the standard drug. The fraction exhibited such efficacy via inhibition of proinflammatory cytokines TNF-α, IFN-γ, by 61.12 and 65.18%, respectively, at 100 μg/mL. Inhibition of cyclooxygenase and Nitric oxide synthase in a dose-dependent manner affirms its analgesic and anti-inflammatory activity. The spectrophotometric analysis reveals that STF-HAETR induces ameliorative effect against heat-induced denaturation of Bovine serum albumin (BSA) and exhibits significant anti-proteinase activity. The plant fraction also demonstrated anti-asthmatic activity by displaying 62.45% protection against histamine induced bronchoconstriction or dyspnoea. Our findings suggest that STF-HAETR could be an effective safe therapeutic agent to treat nociceptive pain, acute inflammation, asthma, and arthritis which may authenticate its traditional use.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9442ddaf92065ac22e068d7db24594c9Test
https://doi.org/10.1007/s10787-017-0403-7Test

المؤلفون: Avanish Tripathi, Sushant K. Shrivastava, Robin Bandresh, Pavan Srivastava, Prabhash Nath Tripathi

المصدر: Bioorganic & Medicinal Chemistry. 25:4424-4432

مصطلحات موضوعية: Male, medicine.drug_class, Lipoxygenase, Clinical Biochemistry, Pharmaceutical Science, Carrageenan, 010402 general chemistry, 01 natural sciences, Biochemistry, Anti-inflammatory, Mice, Structure-Activity Relationship, chemistry.chemical_compound, In vivo, Drug Discovery, medicine, Animals, Edema, Cyclooxygenase Inhibitors, Lipoxygenase Inhibitors, Molecular Biology, IC50, Ulcer, Arachidonic Acid, Dose-Response Relationship, Drug, Molecular Structure, biology, 010405 organic chemistry, Anti-Inflammatory Agents, Non-Steroidal, Organic Chemistry, Indolizines, Zileuton, Rats, 0104 chemical sciences, Disease Models, Animal, chemistry, Prostaglandin-Endoperoxide Synthases, Docking (molecular), Drug Design, biology.protein, Molecular Medicine, Female, Indolizine, Cyclooxygenase, medicine.drug

الوصف: Some novel indolizine derivatives were synthesized by bioisosteric modification of imidazo[1,2-a]pyridine for anti-inflammatory activity. The physicochemical characterization and structure of compounds were elucidated by state of the art spectroscopic technique. Induced fit docking was performed for initial screening to elucidate the interactions with corresponding amino acids of cyclooxygenase (COX-1, COX-2) and lipoxygenase (LOX) enzymes. The target compounds 53-60 were then evaluated against in vivo carrageenan and arachidonic acid induced rat paw edema models for anti-inflammatory activity. Amongst all the synthesized derivatives, compound 56 showed the significant anti-inflammatory activity in both rat paw edema models with very less ulcerogenic liability in comparison to standard diclofenac, celecoxib, and zileuton. The compounds 56 was further assessed to observe in vitro enzyme inhibition assay on both cyclooxygenase and lipoxygenase enzyme where it showed a preferential and selective non-competitive enzyme inhibition towards the COX-2 (IC50=14.91μM, Ki=0.72µM) over COX-1 (IC50>50μM) and a significant non-competitive inhibition of soybean lipoxygenase enzyme (IC50=13.09μM, Ki=0.92µM). Thus, in silico, in vivo, and in vitro findings suggested that the synthesized indolizine compound 56 has a dual COX-2 and LOX inhibition characteristic and parallel in vivo anti-inflammatory activity in comparison to the standard drugs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9f156ee51b62dd398147c3577fcb87eTest
https://doi.org/10.1016/j.bmc.2017.06.027Test

المؤلفون: Rodríguez-Mañas, Leocadio, El-Assar, Mariam, Vallejo, Susana, López-Dóriga, Pedro, Solís, Joaquin, Petidier, Roberto, Montes, Manuel, Nevado, Julián, Castro, Marta, Gómez-Guerrero, Carmen, Peiró, Concepción, Sánchez-Ferrer, Carlos F

مصطلحات موضوعية: aging, cyclooxygenase, endothelium, nitric oxide, nuclear factor kappa-B, peroxynitrite, superoxide, vascular inflammation, Adolescent, Adult, Aged, 80 and over, Vascular, Female, Humans, Inflammation Mediators, Male, Mesenteric Arteries, Middle Aged, NF-kappa B, Oxidative Stress, Prostaglandin-Endoperoxide Synthases, Superoxides, Vasodilation

الوصف: Vascular endothelial dysfunction occurs during the human aging process, and it is considered as a crucial event in the development of many vasculopathies. We investigated the underlying mechanisms of this process, particularly those related with oxidative stress and inflammation, in the vasculature of subjects aged 18-91 years without cardiovascular disease or risk factors. In isolated mesenteric microvessels from these subjects, an age-dependent impairment of the endothelium-dependent relaxations to bradykinin was observed. Similar results were observed by plethysmography in the forearm blood flow in response to acetylcholine. In microvessels from subjects aged less than 60 years, most of the bradykinin-induced relaxation was due to nitric oxide release while the rest was sensitive to cyclooxygenase (COX) blockade. In microvessels from subjects older than 60 years, this COX-derived vasodilatation was lost but a COX-derived vasoconstriction occurred. Evidence for age-related vascular oxidant and inflammatory environment was observed, which could be related to the development of endothelial dysfunction. Indeed, aged microvessels showed superoxide anions (O(2)(-)) and peroxynitrite (ONOO(-)) formation, enhancement of NADPH oxidase and inducible NO synthase expression. Pharmacological interference of COX, thromboxane A(2)/prostaglandin H(2) receptor, O(2)(-), ONOO(-), inducible NO synthase, and NADPH oxidase improved the age-related endothelial dysfunction. In situ vascular nuclear factor-kappaB activation was enhanced with age, which correlated with endothelial dysfunction. We conclude that the age-dependent endothelial dysfunction in human vessels is due to the combined effect of oxidative stress and vascular wall inflammation.

العلاقة: Rodríguez-Mañas, L. et al (2009) 'Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation' Aging Cell 8 (3):226-38; http://hdl.handle.net/10547/593446Test; Aging cell

الإتاحة: https://doi.org/10.1111/j.1474-9726.2009.00466.xTest
http://hdl.handle.net/10547/593446Test

المؤلفون: Jasmine Peter, I S Aswathy, G Pillai Radhakrishna, Monisha Simon, S S Lal Preethi, Santhi Krishnan, Vidya Sabu, Antony Helen

المصدر: Cytokine. 142:155475

مصطلحات موضوعية: CD36 Antigens, Male, 0301 basic medicine, CD36, Interleukin-1beta, Pharmacology, Biochemistry, Cholesterol, Dietary, chemistry.chemical_compound, 0302 clinical medicine, Transforming Growth Factor beta, Betulinic acid, Arachidonate 15-Lipoxygenase, Immunology and Allergy, Apigenin, Aorta, Toll-like receptor, biology, Interleukin-18, Intracellular Signaling Peptides and Proteins, Inflammasome, Hematology, Lipids, 030220 oncology & carcinogenesis, Quinolines, Rabbits, Inflammation Mediators, medicine.symptom, Signal transduction, Pentacyclic Triterpenes, Signal Transduction, medicine.drug, Cell Survival, Immunology, Inflammation, Diet, High-Fat, Thiobarbituric Acid Reactive Substances, 03 medical and health sciences, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, RNA, Messenger, Betulinic Acid, Molecular Biology, Peroxidase, Superoxide Dismutase, Transcription Factor RelA, Atherosclerosis, Toll-Like Receptor 2, TLR2, 030104 developmental biology, chemistry, Prostaglandin-Endoperoxide Synthases, Myeloid Differentiation Factor 88, biology.protein, Nitric Oxide Synthase, Biomarkers

الوصف: Background Progression of chronic inflammatory disease, atherosclerosis is a multifactorial process. Cluster of differentiation 36 (CD36) mediated downstream activation of Toll like receptor 2 (TLR2) and NLRP3 (Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome signaling pathway actively participates during chronic inflammation. Nowadays, synergistic combinations of bioactive compounds attained priority in the field of drug discovery and development as therapeutic agents. An investigation regarding the anti-inflammatory potential of a novel drug formulation, BASk which is a combination of three bioactive compounds Betulinic acid (B):Apigenin (A):Skimmianine (Sk) remains the focus area of this research study. We also elucidate the molecular mechanism behind the therapeutic potential of BASk through CD36 mediated activation TLR2-NLRP3 signaling pathway. Methods OxLDL induced hPBMCs used to screen out a suitable combination of BASk via MTT, COX, LOX, NOS and MPO assays. Hypercholesterolemia is induced in rabbits by supplementing with 1% cholesterol + 0.5% cholic acid and treated with BASk (2:2:1) (5 mg/Kg) and atorvastatin (10 mg/Kg) for 60 days. CD36, TLR2, NLRP3, NFκB, cytokines, endothelial damage were quantified by reverse transcription, real time PCR, ELISA, flow cytometry and histopathology. Results hPBMCs pretreated with BASk at 2:2:1 ratio significantly decreased the activities of COX, 15-LOX, NOS and MPO on OxLDL induction than quercetin. Down regulation of CD36, TLR2, MyD88, TRAF6 by BASk further buttressed NLRP3 inflammasome activation mediated by the transcription factor NFκB. This is in correlation with the effect of BASk by balancing pro (IL-1β, IL-18) and anti-inflammatory (TGF-β) mediators in the aortic endothelial cells. Conclusion BASk exerted its anti-inflammatory potential by reducing pro-inflammatory mediators during cholesterol supplementation via down regulating CD36 mediated TLR2 – NLRP3 inflammasome cascade. This deciphers a synergistic combination named BASk (2:2:1) as a novel drug formulation against chronic inflammatory disease, atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ac84ee1e572e8c585d4adbb830ee73fTest
https://doi.org/10.1016/j.cyto.2021.155475Test

المؤلفون: Murat Yalcin, Gokcen Guvenc-Bayram

المصدر: Neuroscience Letters. 756:135961

مصطلحات موضوعية: Male, 0301 basic medicine, Microdialysis, Lipoxygenase, Hypothalamus, Ibuprofen, Pharmacology, Cardiovascular System, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Western blot, Heart Rate, medicine, Animals, Nucleobindins, Arterial Pressure, Receptor, chemistry.chemical_classification, Cyclooxygenase 2 Inhibitors, Dose-Response Relationship, Drug, medicine.diagnostic_test, biology, General Neuroscience, Rats, Nordihydroguaiaretic acid, 030104 developmental biology, Enzyme, chemistry, Prostaglandin-Endoperoxide Synthases, biology.protein, Cyclooxygenase, 030217 neurology & neurosurgery

الوصف: That nesfatin-1 is a neuromodulatory peptide for the cardiovascular system is well documented. Several central receptors have been shown to mediate the cardiovascular effects of nesfatin-1. Immunohistochemistry and Western blot studies showed that nesfatin-1 activated the expression of the central cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX). In addition, microdialysis study showed that nesfatin-1 increased the release of total prostaglandins and leukotrienes from the hypothalamus. The present study investigated whether the central COX and LOX enzymes have a direct mediating role in the MAP and HR responses of nesfatin-1. Intracerebroventricularly administered nesfatin-1 produced dose-dependent pressor and phasic HR responses in normotensive conscious rats Sprague Dawley. Central pretreatment with a COX1/2 inhibitor, ibuprofen, completely blocked the nesfatin-1-induced responses. However, central pretreatment with a nonselective LOX inhibitor, nordihydroguaiaretic acid, partially attenuated the cardiovascular responses induced by nesfatin-1. The results suggest that centrally administered nesfatin-1 activates the central enzymes COX and LOX, which may be involved in the cardiovascular responses as a novel central mechanism for nesfatin-1.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27b3c8b41dec83d4bb89d3dba8907b37Test
https://doi.org/10.1016/j.neulet.2021.135961Test

المؤلفون: Rocha-Sousa, A., Saraiva, J., Henriques-Coelho, T., Falcão-Reis, F., Correia-Pinto, Jorge, Leite-Moreira, A. F.

مصطلحات موضوعية: Animals, Anterior Eye Segment, Carbachol, Cholinergic Agonists, Dose-Response Relationship, Drug, Epinephrine, Ghrelin, In Situ Hybridization, Iris, Male, Muscle Contraction, Muscle Relaxation, Oculomotor Muscles, Oligopeptides, Peptide Hormones, Potassium Channels, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Rabbits, Rats, Wistar, Receptors, G-Protein-Coupled, Ciliary epithelium, Muscle fibers, Ciências Médicas::Medicina Básica, Science & Technology

الوصف: Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1-5 human ghrelin (frGhr, 10(-9)-6 x 10(-5)M) and 1-5 human des-octanoyl-ghrelin (d-frGhr; 10(-9)-6 x 10(-5)M) were tested on iris rabbit sphincter (n=11 frGhr; n=7 d-frGhr), dilator (n=6 frGhr; n=6 d-frGhr) and rat sphincter (n=6 frGhr; n=8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10(-5)M; n=7); ii) indomethacin (10(-5)M; n=7); iii) DLys(3)GHRP6 (10(-4)M; n=6); and iv) apamin+carybdotoxin (10(-6)M; n=6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys(3)GHRP6 (10(-4)M; n=7). Finally, ghrelin mRNA production was assessed by "in situ" hybridization in Wistar rat eyes (n=8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 x 10(-5)M, 1.5-3 min after its addition, decreasing tension by 34.1+/-12.1%, 25.8+/-4.8% and 52.1+/-10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys(3)GHRP6 (118.1+/-21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin+carybdotoxin (36.4+/-14.4%) or L-NA (52.4+/-11.4%). Relaxing effects of d-frGhr in rabbit (43.3+/-5.2%) and rat (77.1+/-15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K(Ca) ...

وصف الملف: application/pdf

العلاقة: SFRH/BPD/15408/2005; https://www.sciencedirect.com/science/article/pii/S0014483506002946Test; Rocha-Sousa, A., Saraiva, J., Henriques-Coelho, T., Falcao-Reis, F., Correia-Pinto, J., & Leite-Moreira, A. F. (2006). Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles. Experimental eye research, 83(5), 1179-1187; http://hdl.handle.net/1822/67941Test

الإتاحة: https://doi.org/10.1016/j.exer.2006.06.005Test
http://hdl.handle.net/1822/67941Test

المؤلفون: Florentinus, Stefan R, Heerdink, Eibert R, de Boer, Antonius, van Dijk, Liset, Leufkens, Hubert G M, de Boer, Anthonius

المساهمون: Dep Farmaceutische wetenschappen, Sub Pharmacotherapy, Theoretical, Sub Clinical Pharmacy, Pharmacoepi, Sub Gen. Pharmacoepi and Clinical Pharm, Sub Pharmacoepidemiology

مصطلحات موضوعية: Anti-Inflammatory Agents, Non-Steroidal, Arthritis, Cardiovascular Diseases, Comorbidity, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Family Practice, Female, Gastrointestinal Diseases, Humans, Lactones, Male, Membrane Proteins, Middle Aged, Prostaglandin-Endoperoxide Synthases, Retrospective Studies, Risk Assessment, Sulfones

الوصف: BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.

وصف الملف: text/plain

العلاقة: https://dspace.library.uu.nl/handle/1874/11876Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/11876Test

المؤلفون: Woude, C.J. (Janneke) van der, Moshage, H., Homan, M., Kleibeuker, J.H. (Jan), Jansen, P.L.M. (Peter), Dekken, H. (Herman) van

المصدر: Journal of Clinical Pathology: an international peer-reviewed journal for health professionals and researchers in clinical pathology

مصطلحات موضوعية: Apoptosis, Adenocarcinoma/metabolism/pathology, Antigens, CD95/metabolism, Caspases/metabolism, Colitis, Ulcerative/complications/*metabolism/pathology, Colonic Neoplasms/etiology/*metabolism/pathology, Cyclooxygenase 2, Disease Progression, Female, Humans, Inflammation Mediators/metabolism, Male, Membrane Proteins, Middle Aged, Neoplasm Proteins/*metabolism, Nitric Oxide Synthase Type II, Nitric Oxide Synthase/metabolism, Precancerous Conditions/*metabolism/pathology, Prostaglandin-Endoperoxide Synthases/metabolism, Proto-Oncogene Proteins c-bcl-2/metabolism, bcl-X Protein

الوصف: BACKGROUND: Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)-carcinoma sequence. AIMS: To investigate the expression of apoptosis and inflammatory related proteins in CUC. METHODS: The expression of proteins involved in apoptosis and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Bcl-xl, Fas, and active caspase 3) was investigated and compared with that seen in sporadic colon carcinoma. RESULTS: COX-2 was negative in the epithelium of all samples. iNOS was clearly present in inflammatory areas in CUC epithelium, weakly expressed in dysplasia, and absent or weakly expressed in tumour cells. Bcl-xl was absent in CUC, increased in dysplasia, and highly expressed in most carcinomas. Fas expression was positive in the surface epithelium of CUC, dysplasia, and most tumour cells. Activated caspase 3 was weakly positive in all samples, indicating limited apoptosis. Compared with CUC associated carcinoma, iNOS was consistently expressed in sporadic colon carcinoma cells, whereas Bcl-xl was almost absent in these tumour cells and Fas was only weakly expressed. Activated caspase 3 was present in normal mucosal samples and some tumour cells. CONCLUSION: Apoptosis related proteins--particularly iNOS, Bcl-xl, and Fas-show a distinct pattern of expression in the CUC to carcinoma sequence, which differs from that seen in sporadic carcinoma, but bears a striking resemblance to that seen during neoplastic progression in Barrett's oesophagus. These results support a causal role for chronic inflammation in cancer development in CUC, and treatment of ulcerative colitis should aim to minimise inflammation.

وصف الملف: application/pdf

العلاقة: http://repub.eur.nl/pub/8371Test; urn:hdl:1765/8371

الإتاحة: http://repub.eur.nl/pub/8371Test