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The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals. We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation. Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively. [ABSTRACT FROM AUTHOR]

One week after injection of streptozotocin (60 mg/kg intravenously), rats developed diabetes associated with a significant increase of gastric mucosa sensitivity to the ulcerogenic effect of indomethacin (35 mg/kg subcutaneously). Since potentiation of the ulcerogenic effect of indomethacin was observed only in rats subjected to fasting before drug injection, we hypothesize that this effect was caused by a drop of high glucose level in the blood after fasting. [ABSTRACT FROM AUTHOR]

To evaluate, for the first time, the efficacy of copper–indomethacin in the inhibition of aberrant crypt foci formation using the azoxymethane-induced adenocarcinoma model, to examine cell viability in the HCT-116 colorectal cancer cell line, gastrointestinal permeability, mitochondrial oxidative damage, and renal toxicity in rat models. Azoxymethane-induced adenocarcinoma rats were dosed with indomethacin and copper–indomethacin for 28 days and aberrant crypt foci were evaluated. HCT-116 colorectal cancer cells were exposed to indomethacin and copper–indomethacin at 0–250 μg/mL (0–698 μM for indomethacin, and 0–147 μM for copper–indomethacin), and cell viability was measured. Acute gastrointestinal toxicity was measured using gastrointestinal permeability markers, gastrointestinal ulceration and bleeding, and measurement of an acute-phase protein haptoglobin. Effects of acute and chronic administration of indomethacin and copper–indomethacin on urinary electrolyte concentrations were examined. Both indomethacin and copper–indomethacin resulted in a significant reduction in aberrant crypt foci in azoxymethane-treated rats. In parallel, high concentrations of indomethacin and copper–indomethacin also reduced cell viability in HCT-116 colorectal cancer cells. However, copper–indomethacin was considerably safer in all measures of gastrointestinal toxicity compared to indomethacin. In addition, indomethacin reduced urinary electrolytes at an ulcerogenic dose of 10 mg/kg acutely and chronically at 3.0 mg/kg for 28 days, whereas copper–indomethacin at equimolar doses of indomethacin affected urine electrolytes after acute dosing but not after chronic dosing for 28 days. Copper–indomethacin has both gastrointestinal and renal sparing properties while maintaining efficacy in experimental adenocarcinoma. [ABSTRACT FROM AUTHOR]

Drug resistance continues to be a serious problem in cancer therapy. We investigated whether indomethacin, which inhibits cyclooxygenases, is able to overcome doxorubicin resistance in K562/ADR leukemia cells. Indomethacin at 10 μM increased the cytotoxicity of doxorubicin and vincristine in K562/ADR cells. Intracellular glutathione content was elevated in K562/ADR cells. Indomethacin treatment decreased glutathione content and glutathione-conjugates in K562/ADR cells. Increased expression of γ-glutamylcysteine synthetase (γ-GCS) was observed in K562/ADR cells, but this expression was decreased by indomethacin treatment. The activity of the γ-GCS promoter from K562/ADR cells decreased after indomethacin treatment in MDA231 cells. These data strongly suggest that the cyclooxygenase inhibitor indomethacin increases the cytotoxicity of doxorubicin by decreasing the intracellular contents of glutathione and its conjugates with decreasing expression of γ-GCS by inhibiting γ-GCS promoter activity. [ABSTRACT FROM AUTHOR]

Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. A lot of antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. This study aimed to investigate the antiulcer effects of mirtazapine and to determine its relationship with antioxidant mechanisms. The antiulcer activities of 15, 30, and 60 mg/kg mirtazapine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Mirtazapine decreased the indomethacin-induced ulcers significantly at all doses used. Mirtazapine significantly increased the glutathione (GSH) level, which decreased in the control group given only indomethacin. All doses of mirtazapine significantly decreased the catalase (CAT) level in stomach tissue compared to the control. Additionally, all doses of mirtazapine reversed the decrease in the superoxide dismutase (SOD) level in the stomach tissue of control rats. And finally, all doses of mirtazapine decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels significantly compared to the control. In conclusion, the activation of enzymatic and non-enzymatic antioxidant mechanisms and the inhibition of some toxic oxidant mechanisms play a role in the antiulcer effect mechanism of mirtazapine. This new indication of mirtazapine will make it the first-choice drug in depressive patients with gastric ulcers. [ABSTRACT FROM AUTHOR]

Hemicrania continua (HC) is a primary headache disorder characterized by a continuous, unilateral headache that varies in intensity, waxing and waning without disappearing completely. Ipsilateral cranial autonomic features and response to indomethacin are essential features for the diagnosis of HC. We hereby, describe three patients with the clinical phenotypes of HC in whom response to indomethacin was either incomplete or not sustained. We also review the literature especially for the presence of indomethacin response and ipsilateral cranial autonomic features. [ABSTRACT FROM AUTHOR]

Abstract  Indomethacin caused maximum stomach ulceration in mice on the 3rd day, which was associated with reduction of plasma total antioxidant status (TAS), COX-1, COX-2, mucosal PGE2, VEGF, and vWF, along with an increase in endostatin levels. Treatment with the phytochemical allylpyrocatechol (5 mg/kg, p.o. for 3 days) provided significant ulcer healing by reversing these biochemical parameters, as well as increasing the EGF expression more than that observed due to ulceration. Omeprazole (3 mg/kg, p.o. for 3 days) provided a similar healing by improving TAS and mucin levels, without significantly altering the other parameters. [ABSTRACT FROM AUTHOR]

Abstract Purpose  To design and prepare cocrystals of indomethacin using crystal engineering approaches, with the ultimate objective of improving the physical properties of indomethacin, especially solubility and dissolution rate. Materials and Methods  Various cocrystal formers, including saccharin, were used in endeavours to obtain indomethacin cocrystals by slow evaporation from a series of solvents. The melting point of crystalline phases was determined. The potential cocrystalline phase was characterized by DSC, IR, Raman and PXRD techniques. The indomethacin–saccharin cocrystal (hereafter IND–SAC cocrystal) structure was determined from single crystal X-ray diffraction data. Pharmaceutically relevant properties such as the dissolution rate and dynamic vapour sorption (DVS) of the IND–SAC cocrystal were evaluated. Solid state and liquid-assisted (solvent-drop) cogrinding methods were also applied to indomethacin and saccharin. Results  The IND–SAC cocrystals were obtained from ethyl acetate. Physical characterization showed that the IND–SAC cocrystal is unique vis-à-vis thermal, spectroscopic and X-ray diffraction properties. The cocrystals were obtained in a 1:1 ratio with a carboxylic acid and imide dimer synthons. The dissolution rate of IND–SAC cocrystal system was considerably faster than that of the stable indomethacin γ-form. DVS studies indicated that the cocrystals gained less than 0.05% in weight at 98%RH. IND–SAC cocrystal was also obtained by solid state and liquid-assisted cogrinding methods. Conclusions  The IND–SAC cocrystal was formed with a unique and interesting carboxylic acid and imide dimer synthons interconnected by weak N−H⋯O hydrogen bonds. The cocrystals were non-hygroscopic and were associated with a significantly faster dissolution rate than indomethacin (γ-form). [ABSTRACT FROM AUTHOR]

Gastric complications of indomethacin involve generation of reactive oxygen species, which induce gastric mucosal injury via lipid peroxidation of cell membranes. Peroxidation by reactive oxygen species alters the amounts of unsaturated fatty acids in the cell membrane and thus affects membrane fluidity. Indomethacin-induced lipid peroxidation can thus be detected by measuring cellular membrane fluidity by the fluorescence polarization (FP) method. The aim of this study was to elucidate the usefulness of the FP method for detecting indomethacin-induced gastric cellular injury in RGM-1 cells. Indomethacin-treated RGM-1 cells were investigated by conventional cytotoxicity assay, fluorometry of diphenyl-1-pyrenylphosphine (DPPP) to detect lipid peroxidation, and FP. The effects of both a radical scavenger and an initiator on membrane fluidity change (MFC) in RGM-1 cells were examined. The sensitivity of FP in detecting cellular injury was compared with those of DPPP fluorometry and conventional cytotoxicity measurements. Indomethacin caused an increase in MFC as determined by FP before cytotoxicity was detected by conventional methods. The increase in MFC was associated with increased membrane phospholipid peroxidation (MPP) but not with a prostaglandin deficiency, and the increases in both MFC and MPP were prevented by vitamin E. The FP method is potentially useful for detecting cellular injury in vitro. [ABSTRACT FROM AUTHOR]

Abstract  Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy, and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin (IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen peroxide (H2O2). Exposure of C6 cells to 1 mM H2O2 for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2 at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa α-spectrin breakdown product. Immunofluorescent and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well. Treatment of cells with 1 μM MP or 10 μM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 μM MP or 10 μM IM significantly inhibited H2O2 mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal, may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine whether neonatal-perinatal fellowship programs (NFTPs) in the United States vary in indomethacin use for the management of patent ductus arteriosus (PDA) in ≤28 week gestational age infants at birth. A 53-item web-based survey was sent to 84 NFTP directors who received prenotification, followed 2 weeks later by a reminder letter. A total of 56 NFTP directors responded (67% maximum response rate). Wide variation exists in the maximum number of indomethacin courses used to close ductus, use of indomethacin for reopened PDA beyond 14 days, ductal closure definition, contraindications before consideration of indomethacin, interventions for contraindications, and reported ductal closer rate after each indomethacin course. Indomethacin therapy for symptomatic PDA and short course of indomethacin are common practices. Indomethacin use for the management of PDA in premature infants varies among NFTP directors. Practice attitudes may explain variations in ductal closure and ligation rates. Because practice variations may have implications for long-term outcome of vulnerable premature infants, studies relevant to the management of PDA in premature infants are needed. [ABSTRACT FROM AUTHOR]

Leptin, a multifunctional hormone that regulates food intake and metabolic and endocrine responses, has emerged recently as an important modulatory factor in gastric mucosal resistance to injury. In this study, we applied the animal model of gastric mucosal injury caused by indomethacin to investigate the role of endothelin-1 (ET-1) in the mucosal leptin production. Using groups of rats subjected to intragastric administration of indomethacin (at 0–60 mg/kg), we show that gastric mucosal damage reached a maximum 4 h following the drug, and was accompanied by a marked elevation (up to 3.5-fold) in the mucosal leptin level, up to 4-fold enhancement in the expression of endothelin-converting enzyme-1 (ECE-1) activity and up to 4.5-fold increase in ET-1 generation. Pretreatment with phosphoramidon, an inhibitor of ECE-1 activity, not only led to a decline in ECE-1 and ET-1 generation, but also produced a dose-dependent reduction in the mucosal level of leptin and the extent of mucosal damage caused by indomethacin. This effect of phosphoramidon, however, was subject to suppression by the exogenous ET-1 administration. Moreover, a marked drop in the mucosal level of leptin and the reduction in the severity of mucosal damage was attained following pretreatment with ETA receptor antagonist BQ610, but not by ETB receptor antagonist BQ788. The results implicate ET-1 as a key factor in the regulation of leptin production associated with gastric mucosal response to injury, and show that the stimulatory effect of ET-1 on leptin production occurs via ETA receptor activation. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to evaluate bone mineral density (BMD), by use of DXA, and bone turnover, in patients with Bartter syndrome (BS). Ten patients (2 with BS type II and 8 with BS type III) were included in the procedure. Age at study varied between 2 and 30 years. During the studies usual treatment with indomethacin, spironolactone, and potassium chloride was maintained. Results were compared with those obtained in the 20 asymptomatic parents. Height of the patients at the time of the study did not differ from reference values ( Z-score −1.2 to +0.8). Three patients (1 with BS type II and 2 with BS type III) presented reduced lumbar spine BMD or overt osteopenia (BMD Z-scores: −2.3, −1.3, and −1.1). BMD did not correlate significantly with age. Paternal and maternal femoral neck BMD values correlated significantly with lumbar spine BMD of the patients ( r=0.65, P<0.05, and r=0.80, P<0.01). Lumbar spine BMD Z-scores correlated negatively with urinary Ca excretion when values both from patients and parents were jointly analyzed ( r=−0.43, P<0.05). Plasma calcium concentration was significantly higher ( P<0.001) and plasma phosphate Z-score was significantly lower ( P<0.05) in the patients than in the parents. However, no significant differences were observed in values for intact PTH, 1,25 (OH)2D3 and 25 (OH)D3. Intact PTH values correlated positively with BMD Z-scores at lumbar spine ( r=0.45, P<0.05) and at femoral neck ( r=0.63, P<0.01). Age-corrected biochemical markers of bone formation (plasma alkaline phosphatase and osteocalcin concentrations) were normal whereas age-corrected markers of bone reabsorption (urinary PYD and DPD excretion) were significantly higher than parental values ( P<0.01 and <0.05, respectively). We conclude that: (1) reduced BMD is not an exclusive feature of neonatal BS and it can be also observed in classic BS; (2) the loss of bone mineral is not progressive, probably because of the hypocalciuric effect of indomethacin therapy; and (3) this study did not determine whether loss of bone mass is the cause or the consequence of hypercalciuria although the beneficial effect of indomethacin therapy implies the latter. [ABSTRACT FROM AUTHOR]

AIM AND PURPOSE:To evaluate the effects of two NSAIDs on corneal sensitivity and ocular surface in Sjögren's syndrome (SS) patients. METHODS:In all, 20 SS patients with epithelial corneal defects, were randomly divided into two groups: group 1 (10 females, age 35-63 years), treated with 0.1%indomethacin, one drop three times a day; group 2 (nine females, one male, age 38-65 years) treated with 0.1%diclofenac, at the same regimen. No systemic NSAIDs were allowed. Use of tear substitute was allowed. Corneal sensitivity, corneal staining, BUT, and ocular discomfort, were evaluated before and after 15, 30 days of treatment and 7 days after NSAID discontinuation. For statistical analysis, the Student's t-test and Mann-Whitney U test were used. RESULTS:Both groups showed at day 30 a statistically significant reduction of corneal sensitivity (P<0.05), although the diclofenac-treated group showed a statistically significant lower sensitivity if compared to the indomethacin-treated group (P<0.05). Corneal fluorescein score showed a statistically significantly worst alteration in group 2, 7 days after the discontinuation of the therapy (P=0.02). The ocular discomfort score was statistically significantly reduced in both groups starting from day 15 (P<0.05). DISCUSSION:The results indicate that NSAIDs can be useful in resolving symptoms of ocular discomfort in SS patients. However, they should be used with caution and under close monitoring, and the treatment should be promptly discontinued if corneal epithelial defects develop or worsen during treatment.Eye (2005) 19, 535-539. doi:10.1038/sj.eye.6701537 Published online 21 May 2004 [ABSTRACT FROM AUTHOR]

Indomethacin, a common nonsteroidal anti-inflammatory drug, has been shown to enhance radiation-mediated cell-killing effect through the activation of p38 mitogen-activated protein kinase (MAPK). We found that indomethacin strongly reduced the basal level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in HT-29 human colon carcinoma cells. The inhibition of ERK1/2 by indomethacin was only observed in cells with high basal activities of ERK1/2 such as HT-29 cells, but not in cells with low basal activities, such as HeLa. Cell cycle analysis of HT-29 cells exposed with indomethacin showed a partial G1/S arrest and slow DNA synthesis. However, the treatment with NS398, a specific COX-1/2 inhibitor, failed to show any effect on cell cycle, indicating that the inhibition of COX-1/2 is not responsible for cell cycle arrest. Since U0126, a specific inhibitor for MEK1/2, also induced a partial G1/S arrest, the G1/S arrest induced by indomethacin is, at least in part, caused by the inhibition of ERK1/2. Cell proliferation of HT-29 was inhibited by the treatment of U0126 but not in HeLa cells, and the treatment of HT-29 cells with U0126 enhanced radiation sensitivity possibly due to the accumulation of cells in G1 phase. We found that 17-allylamino-17-demethoxygeldanamycin, a geldanamycin delivative, radiosensitized HT-29 cells at a relatively low dose of irradiation, and indomethacin and U0126 further enhanced this effect. Therefore, tumor cells with elevated ERK1/2 activity can be effectively sensitized to radiation treatment by a combinational inhibition of HSP90 and MAPK activity.Oncogene (2005) 24, 3011-3019. doi:10.1038/sj.onc.1208508 Published online 14 February 2005 [ABSTRACT FROM AUTHOR]

The ulcerogenic effect of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the gastrointestinal mucosa was investigated in the presence of a low dose of indomethacin. Indomethacin at 3 mg/kg did not cause any damage in both the stomach and small intestine, despite inhibiting prostaglandin (PG) production. Rofecoxib had no effect on PG production and did not cause any damage in these tissues. In the presence of indomethacin, however, rofecoxib provoked damage in the small intestine but not the stomach. Indomethacin at 3 mg/kg induced hypermotility and COX-2 expression in the intestine but not in the stomach, both in an atropine-sensitive manner. These results suggest that a low dose of indomethacin produces damage in the small intestine but not in the stomach when administered together with rofecoxib. The PG deficiency caused by a low dose of indomethacin produces hypermotility and COX-2 expression in the small intestine, and results in damage when COX-2 is inhibited. It is assumed that the hypermotility response is a key event in the expression of COX-2 and thereby important in the development of mucosal damage in the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

The peroxisome proliferator-activated receptor system is exciting much interest as a novel point of therapeutic intervention in inflammation. Here, the effect of a peroxisome proliferator-activated receptor α agonist, [4-chloro-6-(2,3-xylidine)-pyrimidinylthio]acetic acid (Wy14,643), was examined in arachidonic acid-induced murine ear inflammation. 3-[1-(4-Chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK886, a 5-lipoxygenase inhibitor) and indomethacin (a cyclo-oxygenase inhibitor) were used as reference compounds. Wy14,643 dose dependently inhibited ear swelling and polymorphonuclear leukocyte influx, as did MK886, associated with reduced tissue leukotriene B4 but not prostaglandin E2 levels. Unlike MK886, Wy14,643 did not inhibit ex vivo leukotriene B4 production. However, Wy14,643, but not MK886, induced peroxisomal enzyme activity. Indomethacin was less effective, though tissue prostaglandin E2 but not leukotriene B4 levels were reduced. Again, unlike indomethacin, Wy14,643 did not reduce ex vivo prostaglandin E2 production. However, indomethacin did increase peroxisomal enzyme activity but to a lesser extent than Wy14,643. This study demonstrates that peroxisome proliferator-activated receptor α activation can inhibit arachidonic acid-induced inflammation in part by enhancing degradation of leukotriene B4. [ABSTRACT FROM AUTHOR]

The present study reports clinical and laboratory data of patients with Bartter syndrome at diagnosis and follow-up with emphasis on the long-term benefits and side effects of the pharmacological therapy, which includes indomethacin and potassium supplementation. We followed 12 children, 6 boys, with a median age at diagnosis of 24.5 months (range 7–137 months) and at the end of the study 157.5 months (range 26.0–224.0 months). All children presented with polyuria and polydipsia, dehydration, and metabolic and electrolyte disturbances with failure to thrive. However, at study entry 5 of 12 patients also had hypophosphatemia, which disappeared after a mean time of 50±22.4 months, 3 of 12 had nephrocalcinosis, and 2 of 12 had typical renal cysts. Despite treatment, hypokalemia was persistent in some patients. During long-term follow-up we observed recovery of growth velocity and adequate metabolic and electrolyte balance. However, we noticed renal and gastrointestinal complications: 2 patients had a perforated gastric ulcer, 1 had a gastric ulcer, and gastritis was detected in 3 children. A decreased glomerular filtration rate was observed in 2 patients during follow-up. Our data emphasize the need for regular surveillance of renal function and gastrointestinal endoscopy in these patients. As an alternative to indomethacin, we present our satisfactory preliminary results with rofecoxib. [ABSTRACT FROM AUTHOR]

A new procedure has been developed for the synthesis of indomethacin by the Fischer reaction, based on the acylation of sodium 2-(4-methoxyphenyl)-1-hydrazosulfonate with 4-chlorobenzoyl chloride and subsequent interaction with levulinic acid in the presence of formic acid. [ABSTRACT FROM AUTHOR]

BACKGROUND Gout is a crystal-induced inflammatory joint disease that predominantly affects men aged >40 years. NSAIDs are the most commonly prescribed agents for gout treatment. OBJECTIVE The objective of this study was to assess the efficacy and safety of combination therapy with oral prednisolone and paracetamol, compared with indomethacin and paracetamol, for the treatment of patients with acute gout-like arthritis in an emergency setting. DESIGN AND INTERVENTIONS This Chinese study was randomized, double-blind and controlled, and took place in a hospital emergency department. Patients (age >17 years) who were clinically diagnosed with acute gout-like arthritis between February 2003 and June 2004 were randomly allocated to receive one of two combination treatments: oral prednisolone and paracetamol or oral indomethacin and paracetamol. Patients with comorbidities that would interfere with assessment, and patients diagnosed with dementia, active gastrointestinal symptoms, renal insufficiency (serum creatinine level >200 µmol/l), bleeding disorders, or patients who were receiving treatment with warfarin, were excluded from this study. Follow-up duration was 14 days. OUTCOME MEASURES The primary outcome measure of this study was the decrease in pain scores, length of time to resolution of pain and symptoms, and any adverse effects related to treatment. The need for additional paracetamol and the rate of relapse were the secondary outcome measures. RESULTS A total of 90 patients with acute gout-like arthritis participated in this study and were randomly allocated to receive combination treatment with either prednisolone (30 mg daily for 6 days, n=44) plus paracetamol or indomethacin (75 mg intramuscularly plus 50 mg orally on day 1, followed by 50 mg three times daily for 2 days, tapering to 25 mg three times daily for 2 days, n=46) plus paracetamol. Overall, decreases in pain were similar between the two treatment groups: the mean (± SD) rate of pain decrease with activity, as measured by visual analogue scale (VAS), was 1.7 ± 1.6 mm per day in the indomethacin group and 2.9±2.0 mm per day in the prednisolone group (mean difference 1.2 mm per day, 95% CI 0.4-2.0 mm per day; P=0.0026). Patients who received combination treatment with prednisolone consumed significantly higher amounts of paracetamol compared with the patients in the indomethacin group (mean dose 10.3 g, range 1-21 g versus mean dose 6.4 g, range 1-21 g). Adverse events were more frequent in the indomethacin group, with 29 patients experiencing treatment-related effects in this group compared with 12 patients in the prednisolone group (P<0.05). Rate of relapse was similar between groups. CONCLUSION The authors conclude that combination therapy with oral prednisolone and paracetamol is as effective as combination therapy with oral indomethacin and paracetamol for the treatment of patients with acute gout-like arthritis; the combination of oral prednisolone and paracetamol is associated with fewer adverse events. [ABSTRACT FROM AUTHOR]

We present two term neonates in which intravenous indomethacin usage was associated with successful closure of a persistently patent arterial duct. Both children had congenital heart disease with high pulmonary blood flow following surgical placement of contralateral systemic-pulmonary artery shunts. [ABSTRACT FROM AUTHOR]

Taxanes such as paclitaxel, which are chemotherapeutic drugs, cause dose-dependent painful neuropathy in some patients. We investigated whether coadministration of minocycline and indomethacin produces antinociceptive effects in mice with paclitaxel-induced neuropathic thermal hyperalgesia and if the cannabinoid system is involved. Previously, we reported that coadministration of these two drugs results in antinociception against inflammatory pain at doses where either drug alone lack significant activity. In the current study, we observed that treatment of female mice with indomethacin or minocycline alone did not affect established paclitaxel-induced thermal hyperalgesia, whereas coadministration of the two drugs attenuated it. In male mice indomethacin had some antihyperalgesic activity, whilst minocycline did not. Coadministration of the two drugs had supraadditive antihyperalgesic activity in male mice. Administration of a cannabinoid CB1 receptor antagonist AM 251 blocked the antihyperalgesic effects of the combination of minocycline and indomethacin in both male and female mice. In conclusion our results indicate that coadministration of minocycline and indomethacin abrogates established paclitaxel-induced neuropathic thermal hyperalgesia in mice, and the potentiation of the antinociceptive effects of this combination involves the cannabinoid system. [ABSTRACT FROM AUTHOR]