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Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg(-1) dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults.
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Primary rat renal tubules were isolated from male rat kidneys by collagenase perfusion and the tubules maintained in culture as a suspension by a gyratory culture method.
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Wistar rats were treated orally once daily with 10 mg·kg⁻¹ roflumilast for 4 days. Macroscopic changes were monitored throughout the study and further parameters were analysed at the end of the experiment on day 5. In addition, the effects of concomitant treatment with cyclooxygenase (COX) inhibitors were assessed.
To promote rational drug use in developing countries, it is important to assess drug use pattern using the World Health Organization (WHO) drug use indicators. The aim of this study was to assess the drug prescription patterns at the Medical Outpatient Pharmacy of Hawassa University Teaching and Referral Hospital, using some of the WHO core drug use indicators.
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The results of this study showed that DSME exhibit potential gastroprotective activity probably due to its antioxidant and cytoprotection ability.
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Both caudal anaesthesia and non-steroidal anti-inflammatory drugs have been used in the management of postoperative pain in children. The aim of the present study was to evaluate the combination of caudal analgesia and rectally administered diclofenac in the treatment of pain following minor surgery in children. Thirty-nine, ASA grade 1 or 2, children undergoing inguinal or penoscrotal surgery were randomly assigned to receive either a caudal block using 0.125% bupivacaine with adrenaline or a similar caudal block in combination with rectally administered diclofenac 1 mg.kg-1. Children given a caudal block alone were more likely to need analgesia in the first 24 h postoperatively. It would appear that the combination of a caudal block and rectal diclofenac in children undergoing minor lower abdominal surgery reduces the need for subsequent analgesia.
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Eighty-eight patients having cataract extraction were enrolled in a randomized clinical trial: 42 were given diclofenac eyedrops and 46, placebo. Postoperative inflammation in both groups was graded for 6 months using a dedicated system.
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The primary efficacy variable was the area under the curve for tenderness over the first 3 days. The diclofenac patch was significantly more effective than placebo (p<0.0001). The treatment effect was 64.7 kp h/cm2 (95% confidence interval 48.7 to 80.9) between diclofenac and placebo patches. These results were supported by all secondary efficacy variables. The diclofenac patch produced rapid pain relief as reflected by the time to reach resolution of pain at the injured site which was significantly shorter compared to placebo (p<0.0001). The diclofenac patch was well tolerated. The most frequently observed adverse events were local cutaneous adverse reactions (pruritus, rash) of minor severity occurring with the same frequency as in the placebo group.
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Dissolution behavior of diclofenac sodium (DS) from wax matrix granules (WMGs) prepared using a twin-screw compounding extruder is closely related to swelling ability and solubility of the rate-controlling agent employed. A swellable and soluble (hydroxypropyl)-cellulose (HPC-SL) generates both an expansion of pores inside WMGs and a structural change observed as cracking on the surface of WMGs. These changes are confirmed by mercury porosimetry. Release of DS was increased with an increase in the amount of HPC-SL in WMGs, but only 35% of DS was released from WMGs containing 73% (w/w) NaCl at the 24 h point of the dissolution. Further, no cracking was observed on the surface of NaCl-containing WMGs. A linear relationship between mean dissolution time (MDT) of DS for WMGs containing different types of HPC (HPC-SL, -M, and -H) and swelling abilities suggests that release of DS could be directly controlled by swelling of HPCs. In addition to this result, an application of the exponential model (Mt/M infinity = kt(n)) introduced by Ritger and Peppas (J. Controlled Release 1987, 5, 23-36) to DS release indicates that case II release plays a critical role in HPC-SL-containing WMGs and Fickian release is predominant in NaCl-containing WMGs since the values of n of WMGs containing 73% (w/w) NaCl and 40% (w/w) HPC-SL are 0.41 and 0.71, respectively. These results suggest that proper selection of rate-controlling agents based on their physicochemical properties (such as swelling ability and solubility) is important in designing WMGs with desired dissolution profiles.
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Cyperus scariosus (R.Br) belongs to the family Cyperaceae and it has a diverse medicinal importance. To identify human cyclooxegenase-2 (COX-2) inhibitors from C. scariosus, the rhizome powder was exhaustively extracted with various solvents based on the increasing polarity. Based on the presence and absence of secondary metabolites, we have selected the methanolic extract to evaluate the anti-oxidant and anti-inflammatory activity. The same extract was further subjected to gas chromatography-mass spectroscopy (GC-MS) analysis to identify the active compounds. Binding affinities of these compounds towards anti-inflammatory protein COX-2 were analyzed using molecular docking interaction studies. Phytochemical analysis showed that methanol extract is positive for all secondary metabolites. The antioxidant activity of the C. scariosus rhizomes methanolic extract (CSRME) is half to that of ascorbic acid at 50 µg/ml. The anti-inflammatory activity of CSRME is higher than that of diclofenac sodium salt at high concentration, which is evident from the dose dependent inhibition of bovine serum albumin denaturation at 40 µg/ml-5 mg/ml. GC-MS analysis showed the presence of nine compounds, among all N-methyl-1-adamantaneacetamide and 1,5,diphenyl-2H-1,2,4- triazine form a hydrogen bond interactions with Ser-530 and Tyr-385 respectively and found similar interactions with crystal structure of diclofenac bound COX-2 protein. Benzene-1, 2-diol, 4-(4-bromo-3 chlorophenyl iminomethyl forms hydrogen bond interactions with Thr-199 and Thr-200 as similar to crystallized COX-2 protein with valdecoxib. Collectively our results suggest that CSRME contains medicinally important anti-inflammatory compounds and this justifies the use of this plant as a folklore medicine for preventing inflammation associated disorders.
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Inguinal hernia repair is frequently associated with persistent postoperative discomfort and pain and late discharge from the hospital. We evaluated the postoperative analgesic effect of local wound infiltration with tramadol following herniorrhaphy among adult patients.
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After major shoulder surgery, ropivacaine 0.2% at 2 ml h(-1) with on-demand 5 ml boluses administered via an ultrasound-guided C5-6 root/superior trunk perineural catheter produces similar analgesia, but higher patient satisfaction compared with ropivacaine 0.4%.
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To assess in a multicenter double blind clinical trial the gastroenteroprotective effect of zinc acexamate (ZAC).
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A 66-year-old woman developed severe and recurrent scleritis and uveitis after neodymium:YAG capsulotomy performed 18 months after cataract extraction. Four cracks on the intraocular lens and plastic splinters in the vitreous indicated that excessive laser energy had been used. Inflammation was treated successfully only when a combination of dexamethasone acetate 0.1% drops (Maxidex), drops of diclofenac sodium 0.1% (Voltaren Ophtha), and systemic diclofenac sodium (Voltaren) was used. Inflammation might be explained by chronic irritation of the ciliary body by a displaced haptic or by an immune reaction triggered by damage to the ciliary body at the time of excessive posterior capsulotomy.
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Two thousand eight hundred and eighty-eight cases and 20 000 controls were included. No increased risk was observed with traditional NSAIDs as a group (OR = 1.03; 95% CI, 0.90-1.19), but results varied across individual agents and conditions of use. An increased risk was found with diclofenac (OR = 1.53; 95% CI, 1.19-1.97), in particular when used at high doses (OR = 1.62; 1.06-2.46), over long-term periods (> 365 days; OR = 2.39; 1.52-3.76) and in patients with a high background CV risk (OR = 1.78; 1.23-2.58), as well as with aceclofenac when used at high doses (OR = 1.67; 1.05-2.67), in long-term treatments (OR = 2.00; 1.14-3.53) and in patients with CV risk factors (OR = 2.33; 1.40-3.87). No association was found with ibuprofen (OR = 0.94; 0.76-1.17) or naproxen (OR = 0.68; 0.36-1.29). The concomitant use of aspirin did not show a significant effect modification. Paracetamol did not increase the risk overall (OR = 0.97; 0.85-1.10) or in patients at high CV risk (OR = 0.94; 0.78-1.14).
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The intra-articular injection of iodoacetate into the knee joint of rats produced changes in the articular cartilage which resembled those of osteoarthritis. It caused virtually total loss of many of the oxidative enzymes, indicating inhibition of the main oxidative pathways. Treatment with an anti-rheumatic drug had little early effect but ultimately led to partial restoration of these pathways. The reduced progression of cartilage degradation induced by this drug was accompanied by some unusual histological features.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in a variety of cells, but the mechanism of this effect has not been fully elucidated. We report that diclofenac, a NSAID, induces growth inhibition and apoptosis of HL-60 cells through modulation of mitochondrial functions regulated by reactive oxygen species (ROS), Akt, caspase-8, and Bid. ROS generation occurs in an early stage of diclofenac-induced apoptosis preceding cytochrome c release, caspase activation, and DNA fragmentation. N-Acetyl-L-cysteine, an antioxidant, suppresses ROS generation, Akt inactivation, caspase-8 activation, and DNA fragmentation. Cyclic AMP, an inducer of Akt phosphorylation, suppresses Akt inactivation, Bid cleavage, and DNA fragmentation. LY294002, a PI3 kinase inhibitor, enhances Akt inactivation and DNA fragmentation. Ac-IETD-CHO, a caspase-8 inhibitor, suppresses Bid cleavage and DNA fragmentation. z-VAD-fmk, a universal caspase inhibitor, but not cyclosporin A (CsA), an inhibitor of mitochondrial membrane permeability transition, suppresses DNA fragmentation. These results suggest the sequential mechanism of diclofenac-induced apoptosis of HL-60 cells: ROS generation suppresses Akt activity, thereby activating caspase-8, which stimulates Bid cleavage and induces cytochrome c release and the activation of caspase-9 and-3 in a CsA-insensitive mechanism. Furthermore, we found that 2-methoxyestradiol (2-ME), a superoxide dismutase inhibitor, significantly enhances diclofenac-induced apoptosis; that is, diclofenac combined with 2-ME may have therapeutic potential in the treatment of human leukemia.
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The in vitro penetration of theophylline, sodium diclofenac and benzoic acid through artificial cellulose membrane and eight animal skins was investigated. The intact animal skins including stratum corneum (SC) and viable epidermis were taken from frog, snake with or without scales, nude mice, Sprague-Dawley rat, porcine and human prepuce and thigh skin. The results indicated that the penetration was fastest through cellulose membrane and frog skin and slowest through human prepuce and thigh skin. The snake skin with scales slowed down the penetration rate more significantly than the scaled skin. Benzoic acid was the fastest penetrant through all animal skins. The permeable behaviors of sodium diclofenac through SC and intact skin of snake, porcine and human were compared. In porcine, sodium diclofenac penetrated through SC at a rate 33 times higher than through intact skin, but in snake and human skin, the rate through SC was only 2.2 and 1.6 times higher than through intact ones. This implies that both viable epidermis and SC were the major rate limiting barriers in drug penetration. DSC thermograms and IR spectra showed that the SC of snake, porcine and human thigh were very similar in structure and components. The study suggests that snake skin, porcine skin and human prepuce skin could replace the human skin in in vitro drug penetration experiments.
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Male Sprague-Dawley rats received a single intra-articular injection of MIA into the infrapatellar ligament of the right knee. Subsequently, the rats were treated with normal saline, SHINBARO, and diclofenac once daily for 21 days. Rats treated with normal saline, but not MIA, comprised the control group. Histological changes in the femur of the MIA-induced osteoarthritis rat model were observed by micro-computed tomography scanning and staining with hematoxylin and eosin, and safranin-O fast green. Serum levels of PGE2 and anti-type II collagen antibodies in the MIA-induced osteoarthritis rat model were measured using commercial kits. Protein levels of inflammatory enzymes (iNOS, COX-2), pro-inflammatory cytokines (TNF-α, IL-1β), and inflammatory mediators (NF-κB, IκB) in cartilaginous tissues were determined by western blot analysis.
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The objective of this study was to compare the force required to separate corneal wounds after topical applications of nonsteroidal antiinflammatory drugs (NSAIDs) or corticosteroids. Bilateral central 8-mm long corneal full-thickness incisions in 50 NZW rabbits were closed with five interrupted 10-0 nylon sutures. There were four paired-eye groups: (a) control/control, (b) control/diclofenac sodium (0.1%), (c) control/flurbiprofen sodium (0.03%), and (d) control/prednisolone acetate (1%) treated six times per day for 7 or 21 days. The wound strength was measured by determining the force necessary to separate the incision along its length. The eyes did not differ statistically from their contralateral eye for each group except control/diclofenac (7.98 g/12.32 g) and control/flurbiprofen (6.96 g/11.67 g) at 21 days. The strongest scars occurred after treatment with diclofenac and flurbiprofen, which were similar (p = 0.74). The weakest wounds for each time period were with prednisolone (1.74 g/3.21 g). The diclofenac and flurbiprofen were stronger than prednisolone-treated eyes at 7 days (p = 0.028 and p = 0.023, respectively) and at 21 days (p < 0.001). The bilateral controls were stronger than the prednisolone controls (p = 0.008 at 7 days and p = 0.001 at 21 days). Steroid treatment caused weaker corneal wound scars than did the NSAIDs. Unilateral steroid treatment adversely affected their untreated contralateral eyes. The NSAID-treated wounds were the strongest and stronger than their contralateral control eyes.
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This study was undertaken to determine whether a special postoperative pain administration of tramadol and diclofenac provides any benefits in patients who underwent microsurgical lumbar discectomy.
Upon pyridine application (2.5%, 5%, 10%, 20%, 40% and 80% in saline), dose-dependent increase in EB dye extravasation was observed (increased vascular permeability). In addition, the levels of TNF-α (P<0.01) and IL-6 (P<0.01) were significantly increased compared to control. Furthermore, the histopathology of pharyngeal tissue showed hypertrophy of submucosal glands, severe inflammation of the pharynx characterised by presence of mononuclear cells, neutrophils along with haemorrhages and congestion; however, normal control animals showed normal cytoarchitecture of pharynx. Indeed, dexamethasone (0.25, 0.5 and 1 mg/kg, i.v.) and diclofenac (1, 2.5 and 5 mg/kg, i.v.) showed dose-dependent protection against pyridine-induced pharyngitis. Further, the possible mechanism of pyridine-induced pharyngitis is thought to be primarily mediated through phospholipase A2 and cyclooxygenase (COX) pathway.
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Anti-inflammatory effects of CBE and CFE were assessed using carrageenan-induced and prostaglandin E₂-induced mouse paw edema models. For the anti-thrombotic effect evaluation, carrageenan-induced tail thrombosis model was performed in mice. The extracts were administered intraperitonally (i.p.) at the doses of 100, 200, and 300 mg/kg. The anti-inflammatory effect of Capparis extracts were tested in comparison to 10 mg/kg diclofenac and anti-thrombotic activity to 10 and 100 IU heparin.
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Preemptive analgesia is an important factor in controlling the postoperative pain and avoiding the stress response caused by the surgery. We aim to compare impact of gabapentin and nimesulide on postoperative analgesic consumption on the visual analog scale (VAS) as well as any potential side effects, to those of the placebo group.
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To compare the effect of Homatropine and Diclofenac eye drops for reducing pain after photorefractive keratectomy (PRK).