Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects.
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PMID:Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. 1122 16

The purpose of this study is to show whether selective (celecoxib) and non-selective (piroxicam) inhibitors of COX-2 can alter the morphological and functional changes after the release of a 24 h complete ureteric obstruction in tissue from solitary rat kidney. Forty male Sprague-Dawley rats weighing 225-250 g were used. The animals were divided into four groups. In group 1 rats (control, n=10), only right nephrectomy was performed. Group 2 rats (untreated, n=10) underwent right nephrectomy and the left ureter was completely obstructed. In group 3 rats (celecoxib), the same operation was performed as described for group 2 and than celecoxib was administered by gavage for a period of 24 h. Group 4 rats (piroxicam) underwent the same operation as described for group 2, then piroxicam was administered intramuscularly at least 1 h before the release of the for 24 h complete ureteric obstruction. All animals were then prepared for functional and histopathological studies. The administration of celecoxib produced a significant decrease in blood urea nitrogen levels when compared to the animals receiving piroxicam and the animals with no treatment. Moreover, celecoxib caused a significant decreased in creatinine levels when compared to the untreated group. Urine volume and the urinary sodium values were increased in the celecoxib group when compared with the other groups. The administration of celecoxib and piroxicam caused a significant decrease in the number of interstitial macrophages when compared to the untreated group. The Bowman space was significantly increased in the untreated group when compared with the celecoxib and the piroxicam groups. These studies indicate that celecoxib may be an important factor affecting renal morphological and functional changes after the release of a 24 h complete ureteric obstruction.
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PMID:Renal effects on a solitary kidney of specific inhibition of cyclooxygenease-2 after 24 h of complete ureteric obstruction in rats. 1220 39

Prostanoids exert physiological effects on ureteral contractility that may lead to pressure changes and pain during obstruction. In the present study, we examined whether (1) obstruction changes the expression of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2 in human and rat ureters and (2) administration of a selective COX-2 inhibitor influences the pelvic pressure change after experimental ureteral obstruction. Rats were subjected to bilateral ureter obstruction. Ureters were removed and dissected into a proximal dilated and distal non-dilated segment. RNA and protein were extracted and analyzed for cyclooxygenase expression by quantitative polymerase chain reaction and Western blotting. Human ureter samples were obtained from patients undergoing radical nephrectomy. Rat and human ureteral samples were processed for immunohistochemistry. COX-1, but not COX-2 mRNA, was readily detected in the normal rat ureter. COX-2 mRNA and protein expression was increased in the proximal dilated ureter compared to distal non-dilated ureter. This increased COX-2 expression was associated with increased urinary prostaglandin E2 (PGE2) excretion after release of obstruction. Immunohistochemistry showed increased COX-2 labeling in surface epithelium and smooth muscle layers in both rat and human obstructed ureters compared to control ureters. Furthermore, contractile PGE2-EP1 and thromboxane TP receptors were expressed in ureteral smooth muscle. Systemic treatment with the COX-2 selective inhibitor parecoxib (5 mg/kg/day) attenuated the pelvic pressure increase during obstruction. In summary, COX-2 expression is significantly increased in the ureteral wall in response to obstruction in the rat and human ureter and COX-2 activity contributes to increased pelvic pressure after obstruction.
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PMID:Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction. 1682 Jul 95

Congenital hydronephrosis is a serious disease occurring among infants and children. Besides the intrinsic genetic factors, in utero exposure to a xenobiotic, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been suggested to induce hydronephrosis in rodents owing to anatomical obstruction in the ureter. Here, we report that hydronephrosis induced in mouse pups exposed lactationally to TCDD is not associated with anatomical obstruction, but with abnormal alterations in the subepithelial mesenchyma of the ureter. In the kidneys of these pups, the expressions of a battery of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1beta were up-regulated as early as postnatal day (PND) 7. The amounts of cyclooxygenase (COX)-2 mRNA and protein as well as prostaglandin E2 (PGE(2)) were conspicuously up-regulated in an arylhydrocarbon-receptor-dependent manner in the TCDD-induced hydronephrotic kidney, with a subsequent down-regulation of the gene expressions of Na+ and K+ transporters, NKCC2 and ROMK. Daily administration of a COX-2 selective inhibitor to newborns until PND 7 completely abrogated the TCDD-induced PGE(2) synthesis and gene expressions of inflammatory cytokines and electrolyte transporters, and eventually prevented the onset of hydronephrosis. These findings suggest an essential role of COX-2 in mediating the TCDD action of inducing hydronephrosis through the functional impairment rather than the anatomical blockade of the ureter.
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PMID:Critical role of cyclooxygenase-2 activation in pathogenesis of hydronephrosis caused by lactational exposure of mice to dioxin. 1860 29

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer mortality among women. At present, EOC is treated with one or in a combination of treatments, commonly debulking surgery, combining a platinum-based and a taxane-based therapy; however, the patients have a risk of injury to the bowel, bladder, ureter, and vessels during surgery and many of them suffer from severe adverse effects caused by chemotherapy. Pharmaceutical inhibition of cyclooxygenase (COX) might be an important therapeutic tool in cancer treatment, as COX contributes to cancer progression by upregulating the levels of downstream metabolites. In this review article, we have discussed the role of COX in cancer progression and the therapeutic use of COX inhibitors in the treatment of EOC with subsequent clinical studies and future management. Usually, gonadotropins can promote prostaglandin E2 production in EOC cells via COX-1 and -2 upregulations through the PI3K/AKT signaling pathway. Several reports have shown that treatment of EOC cells with COX-1- and COX-2-specific inhibitors exhibits a therapeutic effect on EOC both in vitro and in vivo. However, more clinical investigations are needed to develop therapeutic COX inhibitors for the prevention and treatment of EOC without adverse effects.
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PMID:Cyclooxygenase Inhibitors in Epithelial Ovarian Cancer Treatment. 2972 50