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Diclofenac
Kinds of Diclofenac Terms modified by Diclofenac Selected AbstractsMINIMAL CHANGE DISEASE AND ACUTE TUBULAR NECROSIS CAUSED BY DICLOFENACNEPHROLOGY, Issue 1 2008KRESIMIR GALESIC [source] Determination of Diclofenac in Urine Samples by Molecularly-Imprinted Solid-Phase Extraction and Adsorptive Differential Pulse VoltammetryELECTROANALYSIS, Issue 15 2007Laura Fernández-Llano Abstract A molecularly imprinted polymer for diclofenac (DCF) was prepared by thermal polymerization over silica beads using 2-(dimethylamino)ethyl-methacrylate as functional monomer. After silica elimination by HF treatment, the polymer was applied to the selective solid-phase extraction of the drug from urine followed by its quantification by adsorptive differential pulse voltammetry. Results indicate that the drug could be selectively extracted from the sample and quantified at clinically relevant concentrations (,g/mL). [source] Structural and functional responses of river biofilm communities to the nonsteroidal anti-inflammatory diclofenacENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2007John R. Lawrence Abstract Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that has been detected widely in surface waters in North America and Europe. The impact of diclofenac on river biofilm communities was investigated at exposures of 10 and 100 ,g L,1 of diclofenac or its molar equivalent in carbon and nutrients. Experiments were carried out with river water during spring and summer using rotating annular reactors as model systems. Diclofenac or nutrients at 10 ,g L,1 were observed to have no significant effect on algal, bacterial, and cyanobacterial biomass in spring, whereas in the summer the nutrient equivalent reduced algal biomass and diclofenac reduced cyanobacterial biomass relative to control biofilms (p < 0.05). In contrast, at 100 ,g L,1 diclofenac or nutrients, the result was increased cyanobacterial and bacterial biomass, respectively, relative to control biofilms in spring. In summer, 100 ,g L,1 diclofenac significantly increased bacterial biomass and the nutrient treatment had no significant effect (p < 0.05); both treatments resulted in increased biofilm thickness. The glycoconjugate composition of the exopolysaccharide matrix was influenced differentially by the treatments in both seasons. Biolog assessments of carbon use indicated that 100 ,g L,1 diclofenac or nutrients resulted in significant depressions in the use of carbon sources in summer and significant increases in spring. Impacts on protozoan and micrometazoan populations also were assessed. Denaturing gradient gel electrophoresis analyses of community DNA and fluorescent in situ hybridization studies indicated that diclofenac had significant effects on the nature of the bacterial community in comparison with control and nutrient-treated river biofilm communities. [source] Kinetics and mechanism of sodium N -halo- p -toluenesulfonamides oxidation of diclofenac in alkaline mediumAICHE JOURNAL, Issue 12 2009Puttaswamy Abstract Diclofenac belongs to a class of drugs called nonsteroidal antiinflammatory drugs. The kinetics and mechanism of oxidation of diclofenac by sodium N -halo- p -toluenesulfonamides viz., chloramine-T and bromamine-T in NaOH medium have been studied at 293 K. Under comparable experimental conditions, reactions with both the oxidants follow identical kinetics with a first-order dependence on each [oxidant]o and a fractional-order dependence on each [diclofenac]o and [NaOH]. Activation parameters have been computed. N -hydroxyldiclofenac is identified as the oxidation product of diclofenac. Michaelis-Menten type of mechanism has been suggested. The rate of oxidation of diclofenac is about four-fold faster with bromamine-T when compared with chloramine-T. This may be attributed to the difference in electrophilicities of Cl+ and Br+ ions and also the van der Waal's radii of chlorine and bromine. Plausible mechanism and related rate law have been designed for the observed kinetics. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Mechanisms of non-steroid anti-inflammatory drugs action on ASICs expressed in hippocampal interneuronsJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Natalia A. Dorofeeva Abstract The inhibitory action of non-steroid anti-inflammatory drugs was investigated on acid-sensing ionic channels (ASIC) in isolated hippocampal interneurons and on recombinant ASICs expressed in Chinese hamster ovary (CHO) cells. Diclofenac and ibuprofen inhibited proton-induced currents in hippocampal interneurons (IC50 were 622 ± 34 ,M and 3.42 ± 0.50 mM, respectively). This non-competitive effect was fast and fully reversible for both drugs. Aspirin and salicylic acid at 500 ,M were ineffective. Diclofenac and ibuprofen decreased the amplitude of proton-evoked currents and slowed the rates of current decay with a good correlation between these effects. Simultaneous application of acid solution and diclofenac was required for its inhibitory effect. Unlike amiloride, the action of diclofenac was voltage-independent and no competition between two drugs was found. Analysis of the action of diclofenac and ibuprofen on activation and desensitization of ASICs showed that diclofenac but not ibuprofen shifted the steady-state desensitization curve to more alkaline pH values. The reason for this shift was slowing down the recovery from desensitization of ASICs. Thus, diclofenac may serve as a neuroprotective agent during pathological conditions associated with acidification. [source] Diclofenac sodium and occlusal splint therapy in TMJ osteoarthritis: a randomized controlled trialJOURNAL OF ORAL REHABILITATION, Issue 10 2008C. MEJERSJÖ Summary, The aim of the study was to compare treatment with diclofenac sodium (Voltaren 3 × 50 mg) to occlusal splint therapy in a randomized, single-blind controlled trial of patients with a diagnosis of temporomandibular joint (TMJ) osteoarthritis (OA) in accordance with Research Diagnostic Criteria for temporomandibular disorders. Patients with general joint disorders or restrictions against medication with non-steroidal anti-inflammatory drug were not included. Twenty-seven females and two males (aged 36,76 years) included, answered a standardized questionnaire and were clinically examined and they underwent TMJ tomography. The treatment was randomized to either splint (n = 15) or diclofenac (n = 14). The temperatures over the TMJs were determined. The patients were re-examined 1 week, 1 month and 3 months after the start of treatment. A 1-year follow-up was carried out using questionnaires. After 1 week of treatment with diclofenac, significant reductions of pain and discomfort, TMJ tenderness and joint pain on jaw movements were noted. The splint therapy gave a significant reduction of reported symptoms after 1 month of treatment. Both treatments gave few adverse effects and were on an equal level. Estimation of the degree of inflammation by measuring the surface temperature over the TMJ was not reliable. Structural changes of the symptomatic TMJs were radiographically found in 82%, the contralateral, symptom-free TMJ had changes in 36%. There was a discrepancy between the clinical and the radiographical findings. Diclofenac gave a more rapid improvement, but both treatments gave a significant reduction of symptoms of TMJ OA within 3 months which remained at the one-year follow-up. [source] Synergistic Effects of Iontophoresis and Jet Injector Pretreatment on the In-vitro Skin Permeation of Diclofenac and Angiotensin IIJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2000KENJI SUGIBAYASHI A non-needle syringe (jet injector) was utilized to increase skin permeation of drugs by iontophoresis. Briefly, physiological saline was initially flushed by the injector to make a pore in the stratum corneum of excised hairless rat skin, and the iontophoretic skin permeation of two model compounds, sodium diclofenac and angiotensin II, was followed using a 2-chamber diffusion cell. Constant voltage and constant current iontophoresis treatments were evaluated. Pretreatment using the jet injector alone resulted in about 13- and 22-fold increases in the steady-state flux of diclofenac and angiotensin II, respectively, through the skin, compared with non-treated controls. Jet injector pretreatment with constant voltage iontophoresis further enhanced skin permeation of diclofenac and angiotensin II, and the enhancement was also greater than that by constant voltage iontophoresis alone. Thus, a synergistic effect was observed. The ratio of enhancement was greater compared with the control. Jet injector pretreatment with constant current iontophoresis, however, did not always yield higher skin permeation of the drugs than injector pretreatment alone, although the lag time was shortened. The difference in the enhancement between the constant voltage- and constant current iontophoresis can be explained by the electric current through the excised skin. Constant current iontophoresis after a short period of constant voltage iontophoresis with multiple jet injector pretreatments may be the best way to increase drug permeability while preventing severe skin damage. [source] CRTH2 mediates the activation of human Th2 cells in response to PGD2 released from IgE/anti-IgE treated nasal polyp tissueALLERGY, Issue 3 2010C. A. Pérez-Novo To cite this article: Pérez- Novo CA, Holtappels G, Vinall SL, Xue L, Zhang N, Bachert C, Pettipher R. CRTH2 mediates the activation of human Th2 cells in response to PGD2 released from IgE/anti-IgE treated nasal polyp tissue. Allergy 2010; 65: 304,310. Abstract Background:, Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D2 (PGD2) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue. Methods:, Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD2. Supernatants were assayed for PGD2 content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP1), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD2 synthase were analysed by real time PCR. Results:, Increased release of PGD2 by nasal polyp tissue treated with IgE/anti-IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD2 synthase, DP1 and CRTH2 receptors increased after stimulation with IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD2 produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. Conclusion:, These data suggest that in immunologically activated nasal polyp tissue, PGD2 produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism. [source] Sequential clot strength analyses following diclofenac in pediatric adenotonsillectomyPEDIATRIC ANESTHESIA, Issue 11 2007MAIREAD HEANEY FCARCSI FJFICM Summary Background:, Tonsillectomy is a common pediatric surgical procedure resulting in significant postoperative pain. There is ongoing controversy as to the most satisfactory analgesic regimen. Nonsteroidal antiinflammatory drugs (NSAIDs) are an alternative to opioids in this setting. NSAID use in tonsillectomy has been shown to be opioid sparing in the recovery period and to have similar analgesic effects to opioids in pediatric patients. Because of their nonspecific action on the enzyme cyclo-oxygenase there is potential for increased bleeding which has led many practitioners to avoid NSAIDs completely in this patient population potentially resulting in suboptimal pain control. Our aim in this study was to assess the effect of preoperatively administered diclofenac on the blood clot strength in children undergoing (adeno-) tonsillectomy. Methods:, Twenty patients undergoing (adeno-) tonsillectomy were recruited into this prospective observational study. All patients received 2 mg·kg,1 of diclofenac rectally immediately preoperatively. Blood was taken for thromboelastograph analysis pre-diclofenac and 1 and 4 h post-diclofenac administration. Results:, There was a statistically significant increase in maximal clot strength (MA) at 1 and 4 h after diclofenac. Similarly there was a statistically significant reduction in time to initial fibrin formation (R time) post-diclofenac. There was no primary or secondary hemorrhage. Conclusions:, Diclofenac when given preoperatively does not adversely affect clot strength in the immediate postoperative period when the risk of primary hemorrhage is greatest. [source] Use of nonsteroidal anti-inflammatory drugs in infants.PEDIATRIC ANESTHESIA, Issue 5 2007A survey of members of the Association of Paediatric Anaesthetists of Great Britain, Ireland Summary Background:, Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as perioperative analgesics. Many are currently used off label. Diclofenac is currently licensed for use in children over 1 year of age for the treatment of juvenile rheumatoid arthritis, while ibuprofen is licensed for use in children weighing over 7 kg. The dose and interval in children is currently extrapolated from adult studies, as the pharmacokinetic (PK) and pharmacodynamic (PD) data are lacking in infants. Methods:, A postal questionnaire was sent to members of the Association of Paediatric Anaesthetist of Great Britain and Ireland seeking to clarify members' prescribing patterns of NSAIDs, especially in infants. Information regarding the choice of NSAIDS, route of administration, lower age limit, dose interval, dose and practice in two specific perioperative contexts (adenotonsillectomy and open heart surgery) was sought. Results:, The response rate was 80%. NSAIDs are used by 86% of responders in infants. Diclofenac is most commonly used intraoperatively (78%); while ibuprofen (73%) was used more frequently postoperatively. NSAIDs are used by 21% of respondents in ICU. Commonest routes of administration were oral (81%) and rectal (80%), rarely intravenously (9%). The commonest dose for diclofena is 1 mg·kg,1 (59%); the dosing schedule employed being 8 hourly in 53% of cases. NSAIDs are used by 57% of responders as part of their analgesic regime for adenotonsillectomies. Conclusion:, Members of the Association of Paediatric Anaesthetists of Great Britain and Ireland commonly prescribe NSAIDs in infants. This is despite the dearth of PK and PD data in this age group. [source] Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgeryPEDIATRIC ANESTHESIA, Issue 6 2000KAHORU NISHINA MD We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2,12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg·kg,1 following oral placebo premedication, i.v. flurbiprofen 1 mg·kg,1 following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg·kg,1 following clonidine, and i.v. flurbiprofen 1 mg·kg,1 following clonidine. The children received clonidine (4 ,g·kg,1) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg·kg,1 i.v. flurbiprofen 1 mg·kg,1, oral clonidine 4 ,g·kg ,1 provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery. [source] More pronounced inhibition of cyclooxygenase 2, increase in blood pressure, and reduction of heart rate by treatment with diclofenac compared with celecoxib and rofecoxibARTHRITIS & RHEUMATISM, Issue 1 2006Burkhard Hinz Objective Recent findings suggest that permanent blockade of cyclooxygenase 2 (COX-2) is one factor contributing to the cardiovascular side effects of selective COX-2 inhibitors (coxibs) and nonsteroidal antiinflammatory drugs (NSAIDs). The present study compared the extent and time course of COX-2 inhibition and the effects on cardiovascular parameters (changes in blood pressure and heart rate) between various antirheumatic doses of diclofenac, celecoxib, and rofecoxib in healthy elderly volunteers. Methods A randomized, parallel-group study was conducted in volunteers receiving 75 mg diclofenac twice daily, 200 mg celecoxib twice daily, or 25 mg rofecoxib once daily for 8 days. Blood samples were obtained predose and at specified time points postdose, on days 1 and 8, for assay of drug plasma concentrations and COX-2 inhibition. Lipopolysaccharide-induced prostaglandin E2 synthesis was measured ex vivo as an index of COX-2 activity in human whole blood. Results COX-2 inhibition was significantly less pronounced after treatment with celecoxib and rofecoxib than with diclofenac. Maximal inhibitions after a single dose and at steady state, respectively, were as follows: 99% and 99% with diclofenac, 70% and 81% with celecoxib, and 56% and 72% with rofecoxib. At steady state, only diclofenac caused virtually complete COX-2 inhibition over the whole dose interval, and this corresponded to the highest increase in systolic blood pressure and greatest reduction in heart rate. Conclusion Diclofenac elicited the most pronounced COX-2 inhibition, blood pressure elevation, and suppression of heart rate. It is assumed that the extent and time course of intravascular COX-2 inhibition may determine the differential profile of cardiovascular side effects associated with NSAIDs and coxibs, but this has to be proven in future studies. [source] Population pharmacokinetics of oral diclofenac for acute pain in childrenBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Joseph F. Standing WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range. , Diclofenac is frequently used ,off-label' in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5,2.5 mg kg,1). There is currently no licensed oral paediatric formulation of diclofenac. WHAT THIS STUDY ADDS , Using a new diclofenac oral suspension, a dose of 1 mg kg,1 in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses. AIMS To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml,1) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children. METHODS 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. RESULTS A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and VD/F were 53.98 l h,1 70 kg,1 and 4.84 l 70 kg,1 respectively. Allometric size models appeared to predict adequately changes in CL and VD with age. Of the simulated doses investigated, 1 mg kg,1 gave paediatric AUC(0,12 h) to adult 50 mg AUC(0,12 h) ratios of 1.00, 1.08 and 1.18 for ages 1,3, 4,6 and 7,12 years respectively. CONCLUSIONS This study has shown 1 mg kg,1 diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses. [source] Diclofenac and acute myocardial infarction in patients with no major risk factorsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2007Susan S. Jick What is already known about this subject ,,We recently published the results of a study on the risk of acute myocardial infarction (AMI) in users of five nonsteroidal anti-inflammatory drugs during the years 2001 to 2005. ,,The results demonstrated, as has been reported in randomized trials, that rofecoxib and celecoxib increase the risk of AMI when taken for at least 10 months. ,,As expected, ibuprofen and naproxen did not materially increase the risk. ,,However, long-term users of diclofenac were at an increased risk of AMI similar to that of users of rofecoxib and celecoxib. What this study adds ,,Extensive use of diclofenac, similarly to rofecoxib and celecoxib, substantially increases the risk of AMI. ,,There is little suggestion of such an effect in users of ibuprofen and naproxen. Aims To explore further a recent finding that long-term users of diclofenac are at increased risk of acute myocardial infarction (AMI) similar to users of rofecoxib and celecoxib. Methods Using the General Practice Research Database, we conducted three separate nested case,control studies of three nonsteroidal anti-inflammatory drugs (NSAIDs) where use started after 1 January 1993 , diclofenac, ibuprofen and naproxen. Cases of AMI were identified between 1 January 1993 and 31 December 2000. Relative risk (RR) estimates for AMI in patients with no major clinical risk factors were determined for each NSAID according to number of prescriptions received compared with one prescription. Results were adjusted for variables possibly related to risk of AMI. Results There was no material elevation of AMI risk according to the number of prescriptions for ibuprofen [RRs and 95% confidence intervals (CIs) 1.0 (0.6, 1.6) and 1.7 (0.9, 3.1) for use of 10,19 and 20+ prescriptions, respectively, compared with one prescription] or naproxen [RRs 1.0 (0.5, 2.2) and 2.0 (0.9, 4.5) for use of 10,19 and 20+ prescriptions, respectively]. However, a substantial increased risk similar to that obtained in our prior study was found in patients who received ,10 prescriptions for diclofenac [RRs 1.9 (1.3, 2.7) and 2.0 (1.3, 3.0) for use of 10,19 and 20+ prescriptions, respectively]. Conclusions Extensive use of diclofenac substantially increases the risk of AMI. There is little suggestion of such an effect in users of ibuprofen and naproxen. [source] Photoallergic contact dermatitis from topical diclofenac in Solaraze® gelCONTACT DERMATITIS, Issue 6 2006L. Kowalzick Solaraze® gel (Shire Deutschland GmbH & Co. KG, Cologne, Germany) containing 3% diclofenac has been licensed in 2001 as a topical treatment for actinic keratoses. It is commonly used in dermatological practice. Undesirable effects are believed to be rare but include pruritus, paresthesia and application-site reactions (dry skin, rash, erythema, contact dermatitis and vesicobullous eruptions). Recently, a few cases of contact dermatitis due to three different allergens including diclofenac have been reported (1,2). [source] Determination of Diclofenac in Urine Samples by Molecularly-Imprinted Solid-Phase Extraction and Adsorptive Differential Pulse VoltammetryELECTROANALYSIS, Issue 15 2007Laura Fernández-Llano Abstract A molecularly imprinted polymer for diclofenac (DCF) was prepared by thermal polymerization over silica beads using 2-(dimethylamino)ethyl-methacrylate as functional monomer. After silica elimination by HF treatment, the polymer was applied to the selective solid-phase extraction of the drug from urine followed by its quantification by adsorptive differential pulse voltammetry. Results indicate that the drug could be selectively extracted from the sample and quantified at clinically relevant concentrations (,g/mL). [source] Hepatotoxicity assay using human hepatocytes trapped in microholes of a microfluidic deviceELECTROPHORESIS, Issue 18 2010Ju Hun Yeon Abstract Hepatocytes have been used for in vitro hepatotoxicity assays because of their ability to sustain intact liver-specific functions. Here, we demonstrate a hepatotoxicity assay system using primary human hepatocytes trapped in microholes of a microfluidic device, providing a microscale in vivo liver-like environment. We performed microfluidic hepatotoxicity assays of several drugs, including acetaminophen, verapamil, diclofenac, and benzopyrene, all of which are known to specifically affect hepatic function. The drug sensitivities in hepatocytes and HepG2 cells were measured by calculating the live cell fraction at various drug concentrations. The results indicated that hepatocytes were more sensitive to these drugs than HepG2 cells. The lethal concentration 50 values for all drugs tested were similar to those from the in vitro toxicity data with human hepatocytes obtained from the literature. Furthermore, we developed a mathematical hepatotoxicity model based on the time-dependent cell death profiles measured by our device. This novel assay system enabled us to analyze in vivo -like hepatotoxicity in a microfluidic device by exploiting microstructures to mimic the microenvironment of the liver. [source] Occurrence and fate of micropollutants in the Vidy Bay of Lake Geneva, Switzerland.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2010Part II: Micropollutant removal between wastewater, raw drinking water Abstract The occurrence and removal of 58 pharmaceuticals, endocrine disruptors, corrosion inhibitors, biocides, and pesticides, were assessed in the wastewater treatment plant (WWTP) of the city of Lausanne, Switzerland, as well as in the effluent-receiving water body, the Vidy Bay of Lake Geneva. An analytical screening method to simultaneously measure all of the 58 micropollutants was developed based on ultra performance liquid chromatography coupled to a tandem mass spectrometer (UPLC-MS/MS). The selection of pharmaceuticals was primarily based on a prioritization study, which designated them as environmentally relevant for the Lake Geneva region. Except for the endocrine disruptor 17,-ethinylestradiol, all substances were detected in 24-h composite samples of wastewater entering the WWTP or in the treated effluent. Of these compounds, 40% were also detected in raw drinking water, pumped from the lake 3,km downstream of the WWTP. The contributions of dilution and degradation to micropollutant elimination between the WWTP outlet and the raw drinking water intake were established in different model scenarios using hypothetical residence times of the wastewater in Vidy Bay of 1, 4, or 90 d. Concentration decrease due to processes other than dilution was observed for diclofenac, beta-blockers, several antibiotics, corrosion inhibitors, and pesticides. Measured environmental concentrations (MECs) of pharmaceuticals were compared to the predicted environmental concentrations (PECs) determined in the prioritization study and agreed within one order of magnitude, but MECs were typically greater than the corresponding PECs. Predicted no-effect concentrations of the analgesic paracetamol, and the two antibiotics ciprofloxacin and sulfamethoxazole, were exceeded in raw drinking water samples and therefore present a potential risk to the ecosystem. Environ. Toxicol. Chem. 2010; 29:1658,1668. © 2010 SETAC [source] Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Meritxell Gros Abstract The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflam-matories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and ,-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60,90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the ,-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low ,g/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption. [source] Structural and functional responses of river biofilm communities to the nonsteroidal anti-inflammatory diclofenacENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2007John R. Lawrence Abstract Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that has been detected widely in surface waters in North America and Europe. The impact of diclofenac on river biofilm communities was investigated at exposures of 10 and 100 ,g L,1 of diclofenac or its molar equivalent in carbon and nutrients. Experiments were carried out with river water during spring and summer using rotating annular reactors as model systems. Diclofenac or nutrients at 10 ,g L,1 were observed to have no significant effect on algal, bacterial, and cyanobacterial biomass in spring, whereas in the summer the nutrient equivalent reduced algal biomass and diclofenac reduced cyanobacterial biomass relative to control biofilms (p < 0.05). In contrast, at 100 ,g L,1 diclofenac or nutrients, the result was increased cyanobacterial and bacterial biomass, respectively, relative to control biofilms in spring. In summer, 100 ,g L,1 diclofenac significantly increased bacterial biomass and the nutrient treatment had no significant effect (p < 0.05); both treatments resulted in increased biofilm thickness. The glycoconjugate composition of the exopolysaccharide matrix was influenced differentially by the treatments in both seasons. Biolog assessments of carbon use indicated that 100 ,g L,1 diclofenac or nutrients resulted in significant depressions in the use of carbon sources in summer and significant increases in spring. Impacts on protozoan and micrometazoan populations also were assessed. Denaturing gradient gel electrophoresis analyses of community DNA and fluorescent in situ hybridization studies indicated that diclofenac had significant effects on the nature of the bacterial community in comparison with control and nutrient-treated river biofilm communities. [source] Seasonality effects on pharmaceuticals and s -triazine herbicides in wastewater effluent and surface water from the Canadian side of the upper Detroit RiverENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2006Wen Yi Hua Abstract The influence of seasonal changes in water conditions and parameters on several major pharmacologically active compounds (PhACs) and s -triazine herbicides was assessed in the wastewater and sewage treatment plant (WSTP) effluent as well as the downstream surface water from sites on the Canadian side of the upper Detroit River, between the Little River WSTP and near the water intake of a major drinking water treatment facility for the City of Windsor (ON, Canada). The assessed PhACs were of neutral (carbamazepine, cotinine, caffeine, cyclophosphamide, fluoxetine, norfluoxetine, pentoxifylline, and trimethoprim) and acidic (ibuprofen, bezafibrate, clofibric acid, diclofenac, fenoprofen, gemfibrozil, indomethacin, naproxen, and ketoprofen) varieties. The major assessed s -triazine herbicides were atrazine, simazine, propazine, prometon, ametryn, prometryn, and terbutryn. At sampling times from September 2002 to June 2003, 15 PhACs were detected in the WSTP effluent at concentrations ranging from 1.7 to 1,244 ng/L. The PhAC concentrations decreased by as much 92 to 100% at the Little River/Detroit River confluence because of the river dilution effect, with further continual decreases at sites downstream from the WSTP. The only quantifiable s -triazine in WSTP effluent, atrazine, ranged from 6.7 to 200 ng/L and was higher in Detroit River surface waters than in WSTP effluent. Only carbamazepine, cotinine, and atrazine were detectable at the low-nanogram and subnanogram levels in surface waters near a drinking water intake site. Unlike the PhACs, atrazine in the Detroit River is not attributable to point sources, and it is heavily influenced by seasonal agricultural usage and runoff. Detroit River surface water concentrations of carbamazepine, cotinine, and atrazine may present a health concern to aquatic wildlife and to humans via the consumption of drinking water. [source] Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscleEXPERIMENTAL PHYSIOLOGY, Issue 4 2005A. Vignaud Non-steroidal anti-inflammatory drugs are frequently prescribed after skeletal muscle injury. It is not known whether this type of medication can interfere with muscle repair, although inflammatory response is thought to play an important role in this process. Tibialis anterior muscles of mice were injured by myotoxic agent (snake venom) or crushed. Then, animals were treated daily for 10,14 days with different types of non-steroidal anti-inflammatory and antioxidant drugs. The long-term repair was studied 10,42 days after injury by analysing the recovery of in situ muscle force production, size of regenerating muscle cells and expression of myosin heavy chain. Our results show that diclofenac, diferuloylmethane (curcumin), dimethylthiourea or pyrrolidine dithiocarbamate treatment did not significantly affect muscle recovery after myotoxic injury (P > 0.05). Similarly, diferuloylmethane, dimethyl sulphoxide or indomethacin administration did not markedly change muscle repair after crush injury. However, we noted that high doses (> 2 mg kg,1) of diferuloylmethane or indomethacin increased lethality and reduced muscle repair after crush injury. In conclusion, non-steroidal anti-inflammatory and antioxidant drugs did not exhibit long-term detrimental effects on muscle recovery after injury, except at lethal doses. [source] A dominant role for chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) in mediating chemotaxis of CRTH2+ CD4+ Th2 lymphocytes in response to mast cell supernatantsIMMUNOLOGY, Issue 3 2006Shân L. Gyles Summary Human cultured mast cells, immunologically activated with immunoglobuin E (IgE)/anti-IgE, released a factor(s) that promoted chemotaxis of human CRTH2+ CD4+ T helper type 2 (Th2) lymphocytes. Mast cell supernatants collected at 20 min, 1 hr, 2 hr and 4 hr after activation caused a concentration-dependent increase in the migration of Th2 cells. The effect of submaximal dilutions of mast-cell-conditioned media was inhibited in a dose-dependent manner by ramatroban (IC50 = 96 nm), a dual antagonist of both the thromboxane-like prostanoid (TP) receptor and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), but not by the selective TP antagonist SQ29548, implicating CRTH2 in mediating the chemotactic response of these Th2 cells. The effect of mast-cell-conditioned media was mimicked by prostaglandin D2 (PGD2) and this eicosanoid was detected in the conditioned media from activated mast cells in concentrations sufficient to account for the activity of the mast cell supernatants. Treatment of the mast cells with the cyclo-oxygenase inhibitor diclofenac (10 ,m) inhibited both the production of PGD2 and the CRTH2+ CD4+ Th2-stimulatory activity, while addition of exogenous PGD2 to conditioned media from diclofenac-treated mast cells restored the ability of the supernatants to promote chemotaxis of these Th2 cells. The degree of inhibition caused by diclofenac treatment of the mast cells was concordant with the degree of inhibition of chemotactic responses afforded by CRTH2 blockade. These data suggest that PGD2, or closely related metabolites of arachidonic acid, produced from mast cells may play a central role in the activation of CRTH2+ CD4+ Th2 lymphocytes through a CRTH2-dependent mechanism. [source] Topical diclofenac in the treatment of actinic keratosesINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2007Hans F. Merk Prof. Dr. Med. First page of article [source] Nicolau Syndrome: three cases and reviewINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2006Kelli Luton MD Nicolau Syndrome, also known as livedo-like dermatitis (LLD) or embolia cutis medicamentosa (ECM), is an infrequent complication following intramuscular and intra-articular injection of various drugs. This rare entity is characterized by severe pain and erythematous-ecchymotic reticular lesions at the injection site, which in many cases lead to necrotic ulcers and scarring. We report three cases of Nicolau Syndrome following injection of diclofenac, penicillin G, and cyanocobalamin. [source] Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratosesINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2001John E. Wolf Jr MD Background Actinic keratoses (AKs) are epidermal skin lesions with the potential to develop into invasive squamous cell carcinoma (SCC). Treatment at an early stage may prevent development of SCC. Current treatment options are highly destructive and associated with significant side-effects. Early studies with topical diclofenac were encouraging and led to its evaluation for the treatment of actininic keratosis. Previous studies have demonstrated that 3% diclofenac in 2.5% hyaluronan gel is effective and well tolerated in the treatment of AK. The present study was designed to further explore the therapeutic potential of this gel. Methods This randomized, double-blind, placebo-controlled trial involved outpatients with a diagnosis of five or more AK lesions contained in one to three 5 cm2 blocks. Patients received either active treatment (3% diclofenac gel in 2.5% hyaluronan gel) or inactive gel vehicle (hyaluronan) as placebo (0.5 g b.i.d. in each 5 cm2 treatment area for 90 days). Assessments included the Target Lesion Number Score (TLNS), Cumulative Lesion Number Score (CLNS), and Global Improvement Indices rated separately by both the investigator (IGII) and patient (PGII). Results Results obtained from 96 patients at follow up (30 days after end of treatment) indicated that a significantly higher proportion of patients who received active treatment had a TLNS = 0 compared to the placebo group (50% vs. 20%; P < 0.001). There was also a significant difference between the two groups in CLNS, with 47% of patients in the active treatment group having a CLNS = 0 compared with only 19% in the placebo group (P < 0.001). The proportion of patients with an IGII score of 4 (completely improved) at follow-up was 47% in the active treatment group compared with only 19% in the placebo group (P < 0.001); for PGII these values were 41% vs. 17%, P < 0.001. Both treatments were well tolerated, with most adverse events related to the skin. Conclusions Topical 3% diclofenac in 2.5% hyaluronan gel was effective and well tolerated for the treatment of AK. [source] A Diversified Library of Bacterial and Fungal Bifunctional Cytochrome P450 Enzymes for Drug Metabolite SynthesisADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2009Roland Weis Abstract Innovative biohydroxylation catalysts for the preparation of drug metabolites were developed from scratch. A set of bacterial and fungal sequences of putative and already known bifunctional P450 enzymes was identified by protein sequence alignments, expressed in Escherichia coli and characterised. Notably, a fungal self-sufficient cytochrome P450 (CYP) from Aspergillus fumigatus turned out to be especially stable during catalyst preparation and application and also in presence of organic co-solvents. To enhance the catalytic activity and broaden the substrate specificity of those variants with high expression levels prominent single mutations were introduced. Selected improved variants were then used as lyophilised bacterial lysates for the synthesis of 4,-hydroxydiclofenac and 6-hydroxychlorzoxazone, the two metabolites of active pharmaceutical compounds diclofenac and chlorzoxazone representing the same metabolites as generated by human P450s. [source] Structure determination of diclofenac in a diclofenac-containing chitosan matrix using conventional X-ray powder diffraction dataJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 2 2004Nongnuj Muangsin The structure determination of diclofenac embedded in a diclofenac-containing chitosan matrix using conventional X-ray powder diffraction data is demonstrated. It reveals that sodium diclofenac, the starting material in the preparation of a controlled-release diclofenac-containing chitosan matrix, changes to diclofenac acid in space group C2/c in the matrix. Simple methods were employed for handling the sample to obtain X-ray powder diffraction data of sufficiently high quality for the determination of the crystal structure of diclofenac embedded in chitosan. These involved grinding and sieving several times through a micro-mesh sieve to obtain a suitable particle size and a uniformly spherical particle shape. A traditional technique for structure solution from X-ray powder diffraction data was applied. The X-ray diffraction intensities were extracted using Le Bail's method. The structure was solved by direct methods from the extracted powder data and refined using the Rietveld method. For comparison, the single-crystal structure of the same drug was also determined. The result shows that the crystal structure solved from conventional X-ray powder diffraction data is in good agreement with that of the single crystal. The deviations of the differences in bond lengths and angles are of the order of 0.030,Å and 0.639°, respectively. [source] Iloprost inhalation redistributes pulmonary perfusion and decreases arterial oxygenation in healthy volunteersACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009D. RIMEIKA Background: Previous studies have shown that ventilation,perfusion matching is improved in the prone as compared with that in the supine position. Regional differences in the regulation of vascular tone may explain this. We have recently demonstrated higher production of nitric oxide in dorsal compared with ventral human lung tissue. The purpose of the present study was to investigate regional differences in actions by another vasoactive mediator, namely prostacyclin. The effects on gas exchange and regional pulmonary perfusion in different body positions were investigated at increased prostacyclin levels by inhalation of a synthetic prostacyclin analogue and decreased prostacyclin levels by unselective cyclooxygenase (COX) inhibition. Methods: In 19 volunteers, regional pulmonary perfusion in the prone and supine position was assessed by single photon emission computed tomography using 99mTc macro-aggregated albumin before and after inhalation of iloprost, a stable prostacyclin analogue, or an intravenous infusion of a non-selective COX inhibitor, diclofenac. In addition, gas distribution was assessed in seven subjects using 99mTc-labelled ultra-fine carbon particles before and after iloprost inhalation in the supine position. Results: Iloprost inhalation decreased arterial PaO2 in both prone (from 14.2±0.5 to 11.7±1.7 kPa, P<0.01) and supine (from 13.7±1.4 to 10.9±2.1 kPa, P<0.01) positions. Iloprost inhalation redistributed lung perfusion from non-dependent to dependent lung regions in both prone and supine positions, while ventilation in the supine position was distributed in the opposite direction. No significant effects of non-selective COX inhibition were found in this study. Conclusions: Iloprost inhalation decreases arterial oxygenation and results in a more gravity-dependent pulmonary perfusion in both supine and prone positions in healthy humans. [source] CYP3A4 is a Human Microsomal Vitamin D 25-Hydroxylase,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Ram P Gupta Abstract The human hepatic microsomal vitamin D 25-hydroxylase protein and gene have not been identified with certainty. Sixteen hepatic recombinant microsomal enzymes were screened for 25-hydroxylase activity; 11 had some 25-hydroxylase activity, but CYP3A4 had the highest activity. In characterized liver microsomes, 25-hydroxylase activity correlated significantly with CYP3A4 testosterone 6,-hydroxylase activity. Activity in pooled liver microsomes was inhibited by known inhibitors of CYP3A4 and by an antibody to CYP3A2. Thus, CYP3A4 is a hepatic microsomal vitamin D 25-hydroxylase. Introduction: Studies were performed to identify human microsomal vitamin D-25 hydroxylase. Materials and Methods: Sixteen major hepatic microsomal recombinant enzymes derived from cytochrome P450 cDNAs expressed in baculovirus-infected insect cells were screened for 25-hydroxylase activity with 1,-hydroxyvitamin D2 [1,(OH)D2], 1,-hydroxyvitamin D3 [1,(OH)D3], vitamin D2, and vitamin D3 as substrates. Activity was correlated with known biological activities of enzymes in a panel of 12 characterized human liver microsomes. The effects of known inhibitors and specific antibodies on activity also were determined. Results: CYP3A4, the most abundant cytochrome P450 enzyme in human liver and intestine, had 7-fold greater activity than that of any of the other enzymes with 1,(OH)D2 as substrate. CYP3A4 25-hydroxylase activity was four times higher with 1,(OH)D2 than with 1,(OH)D3 as substrate, was much less with vitamin D2, and was not detected with vitamin D3. 1,(OH)D2 was the substrate in subsequent experiments. In a panel of characterized human liver microsomes, 25-hydroxylase activity correlated with CYP3A4 testosterone 6,-hydroxylase activity (r = 0.93, p < 0.001) and CYP2C91 diclofenac 4,-hydroxylase activity (r = 0.65, p < 0.05), but not with activity of any of the other enzymes. Activity in recombinant CYP3A4 and pooled liver microsomes was dose-dependently inhibited by ketoconazole, troleandomycin, isoniazid, and ,-naphthoflavone, known inhibitors of CYP3A4. Activity in pooled liver microsomes was inhibited by antibodies to CYP3A2 that are known to inhibit CYP3A4 activity. Conclusion: CYP3A4 is a vitamin D 25-hydroxylase for vitamin D2 in human hepatic microsomes and hydroxylates both 1,(OH)D2 and 1,(OH)D3. [source] | |||||||||||||||||||||||||||||||||||||