The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu-IUD (fixed Cu-IUD) or FICu-IUD (indomethacin-releasing FCu-IUD) was observed by using zymography on SDS-PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu-IUD group were increased significantly as compared with themselves before being inserted FCu-IUD. However, compared with the FCu-IUD group, the activity of some kinds of MMPs in the FICu-IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD-induced menorrhagia and indomethacin reduces IUD-induced menorrhagia by partly inhibiting MMPs synthesis.
Adult ; Endometrium ; enzymology ; Female ; Humans ; Indomethacin ; Intrauterine Devices, Copper ; adverse effects ; Intrauterine Devices, Medicated ; adverse effects ; Matrix Metalloproteinases ; metabolism ; Middle Aged ; Uterine Hemorrhage ; etiology ; prevention & control

The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu-IUD (fixed Cu-IUD) or FICu-IUD (indomethacin-releasing FCu-IUD) was observed by using zymography on SDS-PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu-IUD group were increased significantly as compared with themselves before being inserted FCu-IUD. However, compared with the FCu-IUD group, the activity of some kinds of MMPs in the FICu-IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD-induced menorrhagia and indomethacin reduces IUD-induced menorrhagia by partly inhibiting MMPs synthesis.
Endometrium/*enzymology ; Indomethacin ; Intrauterine Devices, Copper/*adverse effects ; Intrauterine Devices, Medicated/*adverse effects ; Matrix Metalloproteinases/*metabolism ; Uterine Hemorrhage/etiology ; Uterine Hemorrhage/prevention & control

BACKGROUNDAcute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.

METHODSA randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).

RESULTSEtoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).

CONCLUSIONSEtoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).

Adult ; Aged ; Arthritis, Gouty ; drug therapy ; Cyclooxygenase Inhibitors ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Indomethacin ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Pyridines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE₂), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE₂ and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE₂ biosynthesis.
Rats ; Animals ; Stomach Ulcer/pathology* ; Antioxidants/therapeutic use* ; Ranitidine/adverse effects* ; Aesculus ; Ulcer/drug therapy* ; Quercetin ; Plant Extracts/chemistry* ; Indomethacin/therapeutic use* ; Glutathione ; Superoxide Dismutase ; Rutin/adverse effects* ; Prostaglandins/adverse effects* ; Phytochemicals/therapeutic use*

Indomethacin is used widely in clinics nowadays and the side effect of ulceration is well known. This experiment was performed to Study the morphological and histochemical changes on gastric mucosa after indomethacin treatment. The microscopic finding of the mucosa was observed following oral administration of 10 mg/kg indomethacin in alcohol as solvent. The histological changes were observed from 6 hours after administration of indomethacin and the maxima1 injury was found at 24 hours. Structural changes of injury included hemorrhage, epithelial desquamation and inflammatory cell infiltration. From the 3 day specimens, regeneration signs had started and in the 6 day specimens almost complete recovery of the mucosal epithelium was noted. The histochemical changes of the mucus were also observed from the 6 hr specimens. As far as neutral glycoprotein was concerned, the decrease was most significant in the 3 day o1d group, and besides, they showed minimal reaction to PAS stain. For acidic mucus, the decrease was significant in the 24 hr group and the 3 day group showed minimal reaction to Alcian blue stain. It was noted that these changes of the mucus had recovered 6 days after the administration of indomethacin.
Animal ; Gastric Mucosa/drug effects* ; Gastric Mucosa/pathology ; Indomethacin/adverse effects* ; Rats ; Rats, Inbred Strains ; Stomach Ulcer/chemically induced ; Time Factors

OBJECTIVEIntravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants.

METHODSThirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants' clinical course were recorded.

RESULTSThe ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P > 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P < 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC.

CONCLUSIONSOral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC.

Administration, Oral ; Ductus Arteriosus, Patent ; drug therapy ; Enterocolitis, Necrotizing ; epidemiology ; Humans ; Ibuprofen ; administration & dosage ; adverse effects ; therapeutic use ; Indomethacin ; administration & dosage ; adverse effects ; therapeutic use ; Infant, Newborn ; Infant, Premature

Bartter's syndrome is a renal tubular disorder characterized by hypokalemia, metabolic alkalosis, increased urinary excretion of potassium and prostaglandins, a relative vascular resistance to the pressor effects of exogenous angiotensin II, and hyperplasia of the juxtaglomerular apparatus. In most patients, the glomerular filtration rate is normal and chronic renal failure does not develop. We report here on a case of living-related kidney transplantation in Bartter's syndrome, in which a non-steroidal anti-inflammatory drug is suspected to be the cause of the end-stage renal disease.
Adult ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects* ; Bartter's Disease/drug therapy* ; Case Report ; Human ; Indomethacin/adverse effects* ; Kidney Failure, Chronic/surgery* ; Kidney Failure, Chronic/chemically induced* ; Kidney Transplantation* ; Living Donors* ; Male

Non-steroidal anti-inflammatory drugs (NSAIDs) induce tissue damage and oxidative stress in animal models of stomach damage. In the present study, the protective effects of wheat peptides were evaluated in a NSAID-induced stomach damage model in rats. Different doses of wheat peptides or distilled water were administered daily by gavage for 30 days before the rat stomach damage model was established by administration of NSAIDs (aspirin and indomethacin) into the digestive tract twice. The treatment of wheat peptides decreased the NSAID-induced gastric epithelial cell degeneration and oxidative stress and NO levels in the rats. Wheat peptides significantly increased the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and decreased iNOS activity in stomach. The mRNA expression level of μ-opioid receptor was significantly decreased in wheat peptides-treated rats than that in in the control rats. The results suggest that NSAID drugs induced stomach damage in rats, wchih can be prevented by wheat peptides. The mechanisms for the protective effects were most likely through reducing NSAID-induced oxidative stress.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Antioxidants ; pharmacology ; Aspirin ; adverse effects ; Gastric Mucosa ; drug effects ; Gene Expression ; Glutathione Peroxidase ; drug effects ; Indomethacin ; adverse effects ; Male ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase ; chemical synthesis ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Plant Proteins ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, mu ; drug effects ; Stomach ; drug effects ; Superoxide Dismutase ; drug effects ; Triticum ; chemistry

BACKGROUND: We compared indomethacin therapy with the more aggressive approaches of anti-cancer chemotherapy and surgery in the treatment of isolated Langerhans cell histiocytosis (LCH) of bone in children. METHODS: Comparisons were made with respect to healing of the lesion without recurrence, time to radiological healing of the lesion, time to functional recovery, and complications related to treatment. RESULTS: Complete radiologic healing of the lesion (mean, 15.3 months) and functional recovery (mean, 5.6 months) were observed in all patients treated with either approach. No significant differences were noted in the time to complete radiologic healing or the time to functional recovery between the two groups. There were no recurrences with either approach until the last follow-up (mean, 56 months). Complications were common with anti-cancer chemotherapy, but indomethacin was well-tolerated. CONCLUSIONS: Indomethacin seems to be effective for treating isolated LCH of bone in children. Hence, morbidities associated with aggressive treatment approaches such as anti-cancer chemotherapy or surgery can be avoided.
Adolescent ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Bone Diseases/*drug therapy/radiography/radionuclide imaging ; Child ; Child, Preschool ; Cyclooxygenase Inhibitors/*therapeutic use ; Eosinophilic Granuloma/*drug therapy/radiography/radionuclide imaging ; Female ; Humans ; Indomethacin/*therapeutic use ; Infant ; Male ; Recurrence