No abstract available.
Prostaglandin-Endoperoxide Synthases

Background: Earlier studies reported the anti-inflammatory activity in several species of Piper, and Piper umbellatum Linn. leaves containing some phytochemicals that are potent anti-inflammatory agents. However, there was no thorough investigation on the anti-inflammatory activity of the locally grown P. umbellatum in the Philippines. Objective: The study aimed to determine the anti-inflammatory activity of Piper umbellatum leaves using in vitro and in vivo assays. Methodology: Crude extracts were obtained from P. umbellatum leaves using polar and non-polar solvents. The anti-inflammatory activities of all crude extracts were determined using the carrageenan-induced paw edema test in mice and phytochemical analysis. The crude extract with the highest activity was partially purified using column chromatography. The fractions with similar TLC profile were pooled and tested for antiinflammatory activity. COX-1 and COX-2 enzyme inhibitory activity were determined in pooled fractions that showed initial activity in animal model. Results: Among the crude extracts of P.umbellatum, the crude ethyl acetate extract exhibited a significant dose-dependent inhibition on paw edema test with doses of 500 mg/kg bw, 1,000 mg/kg bw and 1,500 mg/kg bw (p<0.05). Among the 20 pooled fractions (PF) collected from the ethyl acetate extract, PF58, PF60 and PF64 had the highest COX-2 enzyme inhibitions of 83.12 %, 84.78% and 77.47%, respectively (p<0.05). PF60 also exhibited the highest anti-inflammatory activity on paw edema with inhibitions of 62.45% at low dose (250 mg/kg bw) and 76.10 % at high dose (1,000 mg/kg bw) in mice. Conclusion The ethyl acetate extract of P. umbellatum leaves and its fraction-PF60 exhibited a significant anti-inflammatory activity in in vitro and in vivo assays and contained high amounts of total phenolic and total flavonoid.
Prostaglandin-Endoperoxide Synthases ; Carrageenan ; Inflammation

No abstract available.
Acute Lung Injury* ; Prostaglandin-Endoperoxide Synthases* ; Sus scrofa*

To study the effect of indomethacin treatment on the reactivity of contact hypersensitivity and discuss relevant mediators which could affect contact hypersensitivity, the following items were evaluated: the change in the plasma concentration of prostsglandin E following indomethacin treatment; the change of contact hypersensitivity following indomethacin treatment. The results ore summarized as follows: 1. The plasma level of prostaglandin E in indomethacin treated mice decreased. 2. The contact hypersensitivity of indomethacin treated mice was depressed. Considering the suppression of contact hyper sensitivity by indomethacin treatment, the metabolites of cyclo-oxygenase such as prostaglandin E may be the possible mediators of induction of contact hypersensitivity.
Animals ; Dermatitis, Contact* ; Indomethacin* ; Mice* ; Plasma ; Prostaglandin-Endoperoxide Synthases

Acetaminophen is a widely used analgesic-antipyretic. Hypersensitivity reactions to acetaminophen are rare and selective sensitivity to acetaminophen without aspirin or non-steroidal antiinflammatory drug intolerance is even rarer. We experienced a case of acetaminopheninduced bronchial asthma without aspirin sensitivity. An oral challenge test upto 650mg of Tylenol demonstrated urticaria and dyspnea with greater than 20% decrease of FEV1. Both oral provocation test with 500mg of aspirin and lysine-aspirin bronchoprovocation test showed negative results. In conclusion, we report a case of acetaminophen-induced asthma without aspirin sensitivity. Cyclo-oxygenase inhibition may not be a pathogenic mechanism of acetaminophen-induced bronchial asthma. Further studies will be needed to clarify the mechanism of this reaction.
Acetaminophen* ; Aspirin* ; Asthma* ; Dyspnea ; Hypersensitivity ; Prostaglandin-Endoperoxide Synthases ; Urticaria

Laser irradiation of the iris can induce acute increase in intraocular pressure (IOP) as well as hypotony. the author evaluated the effect of the prostaglandin on the biphasic IOP response. Of 14 animals, 7 experimental eyes were treated with topical indomethacin(indomethacin group) and 7 experimental eyes received topical saline(no indomethacin group) prior to laser photocoagulation, and the contralateral eyes were used as control eyes. Change in IOP was defined as [IOP of the experimental eye-IOP of the control eye]. Mean change in IOP reached its highest level 1 hour after laser treatment and subsequently decreased in the no indomethacin group(p=<0.0001, repeated measures ANOVA).However, indomethacin pretreatment showed no statistically significant changes throughtout the experimental period as compared with the baseline value(p=0.4, repeated measures ANOVA). Since indomethacin is known to be a potent ingibitor of prostaglandin synthase, our trsults suggest that prostaglandin plays a role on the biphasic IOP change.
Animals ; Indomethacin* ; Intraocular Pressure* ; Iris* ; Light Coagulation ; Prostaglandin-Endoperoxide Synthases

No abstract available.
Cell Proliferation* ; Cyclooxygenase Inhibitors* ; Lipoxygenase* ; Meningioma* ; Prostaglandin-Endoperoxide Synthases*

To study the expression of cyclooxygenase 2 (COX-2) gene and its relationship with clinicopathological characteristics of lung cancer, expression of the COX-2 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in cancerous tissues and paired adjacent non-cancerous tissues from 56 patients and benign lesions from 12 patients. Our results showed that expression of COX-2 gene was detected in a significantly greater proportion of cancerous tissues (60.7%) than adjacent noncancerous tissues (10.7%, P<0.01) and benign lesions (3/12, P<0.05). Expression of COX-2 gene was higher in adenocarcinoma than in squamous carcinoma (P<0.01). There was no significant relationship between COX-2 gene expression and patients' age, sex, histological type of tumors, differentiation degree and TNM stages (P>0.05). The up-regulation of COX-2 gene in lung cancer tissues especially in adenocarcinoma suggested that COX-2 may play a role in the lung carcinogenesis and COX-2 gene may serve as a potential therapeutic target in lung cancer.
Adenocarcinoma/*enzymology ; Cyclooxygenase 2 ; Lung Neoplasms/*enzymology ; Membrane Proteins ; Prostaglandin-Endoperoxide Synthases/*biosynthesis ; Prostaglandin-Endoperoxide Synthases/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Reverse Transcriptase Polymerase Chain Reaction

Prostaglandin E2 (PGE2), a major product of cyclooxygenase, binds to four different prostaglandin E2 receptors (EP1, EP2, EP3, and EP4) which are G-protein coupled transmembrane receptors (GPCRs). Although GPCRs including EP receptors have been shown to be associated with their specific G proteins, recent evidences suggest that GPCRs can regulate MAPK signaling via non-G protein coupled pathways including Src. EP2 is differentially expressed in various tissues and the expression of EP2 is induced by extracellular stimuli. We hypothesized that an increased level of EP2 expression may affect MAPK signaling. The overexpression of EP2 in HEK 293 cells resulted in significant increase in intracellular cAMP levels response to treatment with butaprost, a specific EP2 agonist, while overexpression of EP2 alone did not increase intracellular cAMP levels. However, EP2 overexpression in the absence of PGE2 induced an increase in the level of p38 phosphorylation as well as the kinase activity of p38, suggesting that up-regulation of EP2 may promote p38 activation via non-G protein coupled pathway. Inhibition of Src completely blocked EP2-induced p38 phosphorylation and overexpression of Src increased the level of p38 phosphorylation, indicating that Src is upstream kinase for EP2-induced p38 phosphorylation. EP2 overexpression also increased the Src activity and EP2 protein was co-immunoprecipitated with Src. Furthermore, sequential co-immunoprecipitation studies showed that EP2, Src, and beta-arrestin can form a complex. Our study found a novel pathway in which EP2 is associated with Src, regulating p38 pathway.
Dinoprostone ; GTP-Binding Proteins ; HEK293 Cells* ; Immunoprecipitation ; Phosphorylation* ; Phosphotransferases ; Prostaglandin-Endoperoxide Synthases ; Up-Regulation

PURPOSE: To investigate the degree and effect of cyclooxygenase (COX)-2 expression on the survival of patients with glioblastoma multiforme (GM). MATERIALS AND METHODS: Between 1997 and 2006, thirty consecutive GM patients treated with surgery and postoperative radiotherapy (dose range: 44~65.1 Gy, median dose: 61.2 Gy) were included in the study. Three patients were excluded that discontinued radiotherapy before receiving a dose of 40 Gy due to mental deterioration. The expression of the COX-2 protein in surgical specimens was examined by immunohistochemical analysis. Survival analysis and verification were performed with respect to sex, age, performance status, resection extent, radiotherapy dose, and degree of COX-2 expression using the Kaplan-Meier method and the log rank test. RESULTS: The median length of follow-up was 13.3 months (range: 6~83 months). Staining for COX-2 was positive in all patient samples. Staining for COX-2 that was positive for over 75% of the tumor cells was found in 24 patients. Staining for COX-2 that was positive in less than 25% of tumor cells was found in 3 patients (10.0%), staining for COX-2 that was positive in 25 to 50% of tumor cells was found in 1 patient (3.3%), staining for COX-2 that was positive in 50 to 75% of tumor cells was found in 2 patients (6.7%) and staining for COX-2 that was positive in 75 to 100% of tumor cells was found in 24 patients (80.0%). The median survival and two-year survival rate were 13.5 months and 17.5%, respectively. The survival rate was influenced significantly by the degree of resection (tumor removal by 50% or more) and radiotherapy dose (59 Gy or greater) (p<0.05). The median survival of patients with staining for COX-2 that was positive in less than 75% of tumor cells and in at least 75% of tumor cells was 15.5 and 13.0 months, respectively (p>0.05), and the two-year survival for these groups was 33.3 and 13.3%, respectively (p>0.05). CONCLUSION: The absence of a statistical correlation between the degree of COX-2 expression and survival in GM patients, despite the high rate of COX-2 positive tumor cells in the GM patient samples, requires further studies with a larger series to ascertain the prognostic value of the degree of COX-2 expression in GM patients.
Cyclooxygenase 2* ; Follow-Up Studies ; Glioblastoma* ; Humans ; Prostaglandin-Endoperoxide Synthases ; Radiotherapy ; Survival Rate