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Mu-opioid analgesics are a mainstay in the treatment of acute and chronic pain of multiple origins, but their side effects, such as constipation, respiratory depression, and abuse liability, adversely affect patients. The recent demonstration of the up-regulation and membrane targeting of the delta-opioid receptor (DOR) following inflammation and the consequent enhanced therapeutic effect of delta-opioid agonists have enlivened the search for delta-opioid analgesic agents. JNJ-20788560 [9-(8-azabicyclo-[3.2.1]oct-3-ylidene)-9H-xanthene-3-carboxylic acid diethylamide] had an affinity of 2.0 nM for DOR (rat brain cortex binding assay) and a naltrindole sensitive DOR potency of 5.6 nM (5'-O-(3-[(35)S]thio)triphosphate assay). The compound had a potency of 7.6 mg/kg p.o. in a rat zymosan radiant heat test and of 13.5 mg/kg p.o. in a rat Complete Freund's adjuvant RH test but was virtually inactive in an uninflamed radiant heat test. In limited studies, tolerance was not observed to the antihyperalgesic or antinociceptive effects of the compound. Unlike ibuprofen, JNJ-20788560 did not produce gastrointestinal (GI) erosion. Although morphine reduced GI motility at all doses tested and reached nearly full effect at the highest dose, JNJ-20788560 did not retard transit at the lowest dose and reached only 11% reduction at the highest dose administered. Unlike morphine, JNJ-20788560 did not exhibit respiratory depression (blood gas analysis), and no withdrawal signs were precipitated by the administration of opioid (mu or delta) antagonists. Coupled with the previously published lack of self-administration behavior of the compound by alfentanil-trained primates, these findings strongly recommend delta-opioid agonists such as JNJ-20788560 for the relief of inflammatory hyperalgesia.
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Biochemical tests revealed marked hypokalaemia (serum potassium 1.4 mmol/l) with a metabolic acidosis (pH 7.29). The ECG showed changes of hypokalaemia (ST-segment depression and U wave).
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Nasal fibroblasts were grown from nasal polyp tissue obtained during usual surgical procedure. Fibroblast proliferation was measured by 3H-thymidine incorporation.
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The fungus Verticillium lecanii has previously been shown to be capable of inverting the chirality of ibuprofen and 2-phenylpropionic acid from the (R)-enantiomer to the corresponding (S)-antipode, a phenomenon also observed in mammalian systems including man. An investigation is reported here into the substrate specificity of the enzyme system present in V. lecanii using the following 2-arylpropionic acids: ibuprofen, ketoprofen, indoprofen, suprofen, flurbiprofen and fenoprofen, together with the structurally related compounds 2-phenylbutyric acid, 2-phenoxypropionic acid, mandelic acid, atrolactic acid, etodolac and alpha-methoxyphenylpropionic acid. The results demonstrated that V. lecanii is capable of inverting the chirality of all the 2-arylpropionic acids investigated. All were inverted in the (R) to (S) direction with the exception of ketoprofen, where inversion was observed in the reverse direction. Using the structurally related compounds as substrates, the size of the alkyl substitutent at the alpha-carbon at the methyl group, and the presence of the methyl group at the chiral centre, were found to be critical. These results suggest that V. lecanii could be used as a basis for the production of pure enantiomers of the 2-arylpropionic acids in commercial biotransformations.
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These preliminary findings from a nationally representative survey suggest that among patients refractory to smoking cessation interventions, use of ibuprofen may be useful to decrease CVD risk.
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A quaternary blend (PDGW) composed of polyvinyl pyrrolidone, D,L-lactic acid oligomers, glycerol and water was prepared. The adhesive strength, drug loading capacity, drug state and stability of PDGW were characterized by using ibuprofen (IBU) and salicylic acid (SA) as model drugs. Moreover, In vitro and in vivo drug permeation through rat skin from PDGW patch in comparison to acrylate adhesive (ACA) and nature rubber adhesive (NRA) was investigated.
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Oral ibuprofen is as effective as intravenous ibuprofen for PDA closure even in ELBW infants.
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Human serum albumin (HSA), the most prominent protein in blood plasma, is able to bind a wide range of endogenous and exogenous compounds. Among the endogenous ligands, HSA is a significant transporter of heme, the heme-HSA complex being present in blood plasma. Drug binding to heme-HSA affects allosterically the heme affinity for HSA and vice versa. Heme-HSA, heme, and their complexes with ibuprofen have been characterized by electronic absorption, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy. Comparison of the results for the heme and heme-HSA systems has provided insight into the structural consequences on the heme pocket of ibuprofen binding. The pentacoordinate tyrosine-bound heme coordination of heme-HSA, observed in the absence of ibuprofen, becomes hexacoordinate low spin upon ibuprofen binding, and heme dissociates at increasing drug levels. The electronic absorption spectrum and nu(Fe-CO)/nu(CO) vibrational frequencies of the CO-heme-HSA-ibuprofen complex, together with the observation of a Fe-His Raman mode at 218 cm(-1) upon photolysis of the CO complex and the low spin EPR g values indicate that a His residue is one of the low spin axial ligands, the sixth ligand probably being Tyr161. The only His residue in the vicinity of the heme Fe atom is His146, 9 A distant in the absence of the drug. This indicates that drug binding to heme-HSA results in a significant rearrangement of the heme pocket, implying that the conformational adaptability of HSA involves more than the immediate vicinity of the drug binding site. As a whole, the present spectroscopic investigation supports the notion that HSA could be considered as the prototype of monomeric allosteric proteins.
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Studies of speed, resolution, and selectivity have shown that packed column supercritical fluid chromatography (PCSFC) is a viable technique for the isocratic, isothermal and isobaric separation of seven anticonvulsants, viz., phenobarbitone, phenytoin sodium, phethenylate sodium, nitrazepam, clonazepam, carbamazepine, and primidone, and their simultaneous estimation. The drugs were eluted from a JASCO, RP-C(18) (250 x 4.6 mm) 10 micro packed column with a binary mobile phase of carbon dioxide and methanol, using ibuprofen as the internal standard. The effect of pressure, temperature, modifier concentration, and the rate of flow of CO(2) on retention and selectivity of all the analytes were studied and the parameters optimised. Without methanol in the mobile phase none of the solutes eluted. Changing modifier concentration was the most effective physical parameter for changing retention and selectivity. The analytes were detected using a UV detector at 215 nm. An arbitrary mixture of eight components was baseline resolved in approximately 7 min. The study includes a successful attempt at quantification of the drugs. Chromatographic and analytical figures of merit have been listed. The present work holds promise for a possible replacement of HPLC with SFC for the separation and assay of drugs of different families.
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The great (154, 76%), short 37 (18%), and accessory 12 (6%) saphenous veins were ablated, achieving a 97% clinical success rate. Postoperative complications were few (mild induration and ecchymosis) and well tolerated (no DVT or nerve injury). Of the 6 (3.0%) recanalized target veins, 4 were only partially open and successfully treated with sclerosis. Of the 18 patients with active ulceration, 15 (83%) demonstrated healing after ELAS. In a satisfaction survey of patients more than 1 year after ELAS treatment, 84% of the 31 responders claimed their symptoms had diminished to none or minimal; 97% were mostly or very satisfied with their treatment results.
The wastewater contamination of a Swiss university hospital by active pharmaceutical ingredient (API) residues was evaluated with a three months monitoring campaign at the outlet of the main building. Flow-proportional samples were collected with an automatic refrigerated sampler and analyzed for 15 API, including antibiotics, analgesics, antiepileptic and anti-inflammatory drugs, by using a validated LC-MS/MS method. The metals Gd and Pt were also analyzed using ICP-MS. Measured concentrations were compared to the predicted ones calculated after the drug average consumption data obtained from the hospital pharmacy. The hospital contribution to the total urban load was calculated according to the consumption data obtained from city pharmacies. Lastly, the environmental hazard and risk quotients (RQ) related to the hospital fraction and the total urban consumption were calculated. Median concentrations of the 15 selected compounds were ranging from 0.04 to 675 μg/L, with a mean detection frequency of 84%. The ratio between predicted and measured environmental concentrations (PEC/MEC) has shown a good accuracy for 5 out of 15 compounds, revealing over- and under-estimations of the PEC model. Mean daily loads were ranging between 0.01 and 14.2g/d, with the exception of paracetamol (109.7 g/d). The hospital contribution to the total urban loads varied from 2.1 to 100% according to the compound. While taking into account dilution and removal efficiencies in wastewater treatment plant, only the hospital fraction of the antibiotics ciprofloxacin and sulfamethoxazole showed, respectively, a high (RQ>1) and moderate (RQ>0.1) risk for the aquatic ecosystems. Nevertheless, when considering the total urban consumption, 7 compounds showed potential deleterious effects on aquatic organisms (RQ>1): gabapentin, sulfamethoxazole, ciprofloxacin, piperacillin, ibuprofen, diclofenac and mefenamic acid. In order to reduce inputs of API residues originating from hospitals various solutions can be envisioned. With results of the present study, hospital managers can start handling this important issue.
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Gout attacks resolve in 3 to 10 days without treatment. Treatment is mainly empirical. Paracetamol and application of ice can be tried. If they fail, the best options is a moderate dose of ibuprofen, and NSAID with well-documented adverse effects.
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Twelve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of the following: ketoprofen 3 x 25 mg per day, or ketoprofen 3 x 50 mg per day, or ibuprofen 3 x 200 mg per day, or ibuprofen 3 x 400 mg per day. The response criteria, determined before and on the 2nd day of each treatment period, were: maximal platelet aggregation in response to 1.0 mmol.l-1 arachidonic acid measured by the method of Born and Cross, thromboxane B2 (TXB2) concentration in platelet-rich plasma after aggregation measured by radioimmunoassay, and PGE-M, the index metabolite of total body prostaglandin E2 (PGE2) production, assessed by gas chromatography/tandem mass spectrometry using 18O2-PGE-M as internal standard.
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Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo. No serious GI complications were reported.
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No therapy-associated complications were observed during the study. After 26 weeks, quality of life significantly increased in groups 2 and 3 compared with group 1 (p<0.001). Pain intensity decreased in group 1 by only 6 points, whereas it decreased in group 2 by 31 points and in group 3 by 24 points. Pain relief was significantly different between the treatment groups and the control group and between the treatment groups themselves (p<0.001 and p<0.01).
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A series of novel ether-linked bis(heterocycle)s have been synthesized via [3+2]-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition reaction of nitrile imine with carbonyl group. All the newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Among the list of compounds (7a-k) studied, 7d, 7g, 7j, and 7k exhibited excellent activity comparable to ibuprofen and aspirin at the similar dosages.
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Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher.
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Highly branched, functionalized polymers have potential to act as efficient drug carrier systems. Dendrimers are ideal candidates among model hyperbranched polymers because of their well-defined structure and high density of functional groups. Using ibuprofen as a model drug, we studied the interaction between the drug and Polyamidoamine (PAMAM) dendrimers (generations 3 and 4 with --NH2 functionality) and Perstrop Polyol (generation 5, hyperbranched polyester with --OH functionality). FTIR and NMR studies suggest that ibuprofen predominantly forms a complex with PAMAM dendrimers because of the ionic interaction between the --NH2 end groups and the carboxyl group of ibuprofen. On an average, up to 78 molecules of ibuprofen could be incorporated into one molecule of PAMAM-G4-NH2 with 64 end groups. This complex is stable in deionized water and methanol. The in vitro release of ibuprofen from drug-dendrimer complex is appreciably slower compared to pure ibuprofen. The complexed drug enters A549 cells much more rapidly than pure drug suggesting that dendrimers may be able to carry the complexed drug inside cells efficiently. Hyperbranched Polyol (with 128 --OH end groups) appears to encapsulate approximately 24 drug molecules. Perhaps the lack of strong interactions between the --OH end groups and the drugs prevents complex formation.
There is evidence with a moderate risk of bias that recommends the use of lumiracoxib for acute postoperative dental pain. However, the adverse effects are not completely known. Given that lumiracoxib is currently available in only three countries, further studies are likely to be rare and discouraged.
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Prostaglandin synthesis is catalyzed by a constitutive cyclo-oxygenase isoform (COX-1) and an inducible isoform (COX-2). It is hypothesized that the analgesic and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (nonspecific COX-1/COX-2 inhibitors) such as ibuprofen principally derive from COX-2 inhibition. The purpose of this study was to evaluate steady-state pharmacokinetics, biochemical selectivity and tolerability of rofecoxib (Vioxx), characterized in vitro as a COX-2 inhibitor.
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This Icelandic nationwide registry-based study amounting to 163,406 patient-years showed increased risk of cardiovascular events, i.e. cerebral infarction, myocardial infarction and unstable angina pectoris, among rofecoxib and naproxen users in comparison to diclofenac users. The added risk was most pronounced in young adults using rofecoxib.
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The laboratory tests showed severe hyponatremia ( 111 mmol/l ) and hypoosmolalitiy of the serum. The osmolality of the urine was high (314 mosm/kg). Radiological examination revealed pulmonary as well as cerebral edema.
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It is generally accepted that males and females respond differently to painful conditions. With few exceptions, according to the published literature, females demonstrate a lower pain threshold and a lower tolerance of painful stimuli. There is some support in the literature that females experience greater analgesic efficacy than do males after the administration of narcotic analgesics. We compared the analgesic response of females and males to ibuprofen in a post-third-molar extraction dental pain model.
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The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD.
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This is a case report of a 16-year-old boy with possible drug-induced pancreatitis (DIP) caused by ibuprofen. The patient had a history of psychiatric, but no somatic, disease, and he was admitted with a clinical presentation consistent with acute pancreatitis after a bolus ingestion of 10 g of ibuprofen in a suicidal attempt. No evidence of other causality for acute pancreatitis was identified. The patient was treated with a standard pancreatitis treatment regime and was discharged against medical advice after four days. The case represents a possible causality between ibuprofen and DIP.