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Ibuprofen augments bradykinin-induced glycoconjugate secretion by human nasal mucosa in vivo.

Baraniuk JN, Silver PB, Kaliner MA, Barnes PJ.

Department of Thoracic Medicine, National Heart & Lung Institute, London, England.

Bradykinin (BK) stimulates vascular permeability and glycoconjugate secretion in human nasal mucosa. Since some of the effects of BK may be mediated by autocrine generation of arachidonic acid metabolites, the influence of ibuprofen, a cyclooxygenase inhibitor, on BK-induced nasal secretion was studied. Six normal male subjects had nasal provocations with 0, 10, 100, and 1000 nmol of BK before and after treatment with 400 mg of ibuprofen. Secretions were collected by nasal lavage. Total protein (marker of protein secretion), glycoconjugate (mucous cell marker), lysozyme (serous cell marker), and albumin (marker of vascular permeability) were measured. Basal glycoconjugate secretion was higher after ibuprofen (219 +/- 32 micrograms/ml) than before (81 +/- 56 micrograms/ml; p less than 0.05 by analysis of variance). BK stimulated significant, dose-dependent albumin, total protein, and glycoconjugate secretion. Lysozyme secretion was not stimulated. BK (1000 nmol) significantly increased total protein secretion, tenfold to twentyfold, and albumin secretion by 40-fold to 60-fold. Ibuprofen did not alter BK-induced total protein or albumin secretion. Glycoconjugate secretion after ibuprofen treatment was significantly higher than normal at 10 nmol (p less than 0.05), 100 nmol (p less than 0.02), and 1000 nmol of BK (519 micrograms/ml +/- 74 versus 213 +/- 15 micrograms/ml; p less than 0.05). Therefore, BK induces vascular permeability and exocytosis from glycoconjugate-containing cells but does not stimulate serous cells. Ibuprofen increases baseline secretion of glycoconjugate and enhances BK-induced glycoconjugate secretion. Ibuprofen does not alter BK-induced vascular permeability.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1583245&dopt=Abstract ibuprofen Motrin



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The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat.

Zhao B, Geisslinger G, Hall I, Day RO, Williams KM.

Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, Australia.

The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta-oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1586584&dopt=Abstract ibuprofen Motrin



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Effect of cyclooxygenase inhibition on amphotericin B-induced lung injury in awake sheep.

Hardie WD, Wheeler AP, Wright PW, Swindell BB, Bernard GR.

Vanderbilt University, Nashville, Tennessee.

Amphotericin therapy in humans has been reported to cause severe pulmonary dysfunction in some patients, and these abnormalities have been reproduced in unanesthetized sheep. To determine the role of cyclooxygenase products in this response, paired, random-order experiments in 11 sheep were done using the cyclooxygenase inhibitor ibuprofen. Ibuprofen blunted increases in pulmonary artery pressure (Ppa) after amphotericin (peak Ppa 38 +/- 3 cm H2O in amphotericin-alone group vs. 30 +/- 1 cm H2O in ibuprofen + amphotericin group, P less than .05) and reduced peak lung lymph flow to approximately 170% of baseline compared with 350% of baseline in amphotericin-alone group (P less than .05). In addition, the increase in airflow resistance across the lung and the decrease in partial pressure of oxygen seen after amphotericin was blocked by ibuprofen. Therefore, amphotericin-induced lung dysfunction is produced in part through the generation of cyclooxygenase products of arachidonic acid metabolism and can be ameliorated by pretreatment with the cyclooxygenase inhibitor ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1607684&dopt=Abstract ibuprofen Motrin



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Prevention of cataract in diabetic rats by aspirin, paracetamol (acetaminophen) and ibuprofen.

Blakytny R, Harding JJ.

Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.

Evidence from epidemiological, in vitro and animal studies has accumulated to support the idea that aspirin, ibuprofen and paracetamol protect against cataract. In this study rats made diabetic with streptozotocin were given these drugs in their drinking solution for up to 160 days. All three drugs delayed cataract formation assessed by slit-lamp examination for a large part of this time. Blood glucose levels were a little lower in diabetic rats treated with aspirin and ibuprofen than in untreated diabetic rats although all groups remained diabetic. Similarly, the increased glycation (non-enzymic glycosylation) of lens proteins caused by diabetes was less in the diabetic rats treated with aspirin and ibuprofen. The fall in glutathione induced by diabetes was also alleviated by aspirin and ibuprofen. Paracetamol appeared to afford similar protection against the biochemical changes but its effect was not statistically significant. The decrease in glutathione and increase in glycation were related to the progression of lens opacification. The greatest loss of glutathione occurred at an early stage, whereas glycation had its greatest change at the later stages--nuclear and mature cataract. These results encourage the view that ibuprofen, aspirin and paracetamol could protect against cataract in man: a hypothesis that could be tested in a properly-conducted clinical trial.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1623937&dopt=Abstract ibuprofen Motrin



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Effect of ibuprofen on the healing and remodeling of bone and articular cartilage in the rabbit temporomandibular joint.

Obeid G, Zhang X, Wang X.

Department of Oral and Maxillofacial Surgery, Washington Hospital Center, Washington, DC 20010.

The purpose of this study was to determine the effect of ibuprofen on the healing and remodeling of bone and cartilage in the temporomandibular joint of the rabbit. Forty-two rabbits were operated on to create a groove and a hole in the articular surface of both the right and left mandibular condyles. Following surgery, the animals were divided into three groups. Group A (12 rabbits) was used as a control and the animals did not receive any medication. Group B (15 rabbits) was given a daily dose of 17 mg/kg of ibuprofen. Group C (15 rabbits) was given a daily dose of 34 mg/kg of ibuprofen. All animals were killed after 4 weeks. The 84 condyles were examined clinically and histologically. Statistical analysis showed a highly significant difference in the healing of bone and cartilage between groups A and C (P less than .01) and a significant difference between groups A and B (P less than .05). The results of this study indicate that ibuprofen has an adverse effect on the healing of bone and cartilage in the temporomandibular joint of the rabbit.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1634976&dopt=Abstract ibuprofen Motrin



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Delayed cyclo-oxygenase blockade reduces the neutrophil respiratory burst and plasma tumor necrosis factor levels in sepsis-induced acute lung injury.

Carey PD, Leeper-Woodford SK, Walsh CJ, Byrne K, Fowler AA, Sugerman HJ.

Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23229.

Ibuprofen pretreatment attenuates the enhanced neutrophil (PMN) respiratory burst and reduces increased plasma tumor necrosis factor (TNF) activity in porcine sepsis-induced acute lung injury (ALI). These septic responses have been linked to increased alveolar-capillary membrane (ACM) permeability. This study was designed to establish whether delayed ibuprofen treatment would have the same effect and to examine the relationship between PMN oxidant generation and TNF. Three groups of anesthetized, ventilated pigs (15-25 kg) were used. Group Ps received Pseudomonas aeruginosa (5 x 10(8) CFU/mL at 0.3 mL/20 kg/min) for one hour IV; The control group (Con) received 0.9% NaCl. Group D-Ibu received ibuprofen 12.5 mg/kg as a delayed bolus at 30 minutes and again at 120 minutes after Ps. Protein (BAL-P, microgram/mL) in harvested bronchoalveolar lavage fluid and extravascular lung water (EVLW, mL/kg) were used to estimate the integrity of the ACM. Superoxide anion (O2-) generation (ferricytochrome c reduction) from circulating PMNs and plasma TNF activity (L929 fibroblast bioassay) were measured. The EVLW increased significantly (p less than 0.05), as did BAL-P (p less than 0.01), in the P. aeruginosa-treated animals at 300 minutes. These increases were abolished in Group D-Ibu: EVLW, 6.6 +/- 1.0 baseline vs. 14.6 +/- 2.6 Ps 300 vs. 6.8 +/- 0.9 D-Ibu 300; BAL-P, 175 +/- 28 baseline vs. 984 +/- 186 Ps 300 vs. 284 +/- 42.8 D-Ibu 300. Both enhanced PMN oxidant activity and increased plasma TNF activity were significantly attenuated by delayed ibuprofen treatment. These data support the efficacy of the nonsteroidal anti-inflammatory drug, ibuprofen, when used after the onset of a septic stimulus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1647464&dopt=Abstract ibuprofen Motrin



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Ibuprofen therapy in experimental porcine gram-negative septic shock.

Griffin MP, Gore DC, Lobe TE, Flynn JF, Traber DL, Herndon DN.

Department of Pediatrics, University of Texas Medical Branch, Galveston.

To evaluate the effects of ibuprofen on gram-negative septic shock, immature piglets were subjected to fecal-Escherichia coli peritonitis. Group I (n = 5) received a 12.5 mg/kg bolus of ibuprofen in 0.9% benzyl alcohol, followed by a continuous infusion of 6.25 mg/kg/h. Group II (n = 5) received the vehicle, benzyl alcohol, and Group III (n = 5) received lactated Ringer's solution. Mean survival times among the three groups were not significantly different. Ibuprofen-treated animals had a mean survival time (+/- S.E.M.) of 17.1 +/- 2 h vs. 19.2 +/- 2.4 h in the benzyl alcohol group and 15.7 +/- 2.7 h in the animals receiving lactated Ringer's solution. Thromboxane B2 levels were not significantly different in the treatment vs. non-treatment groups while 6-keto-PGF1a levels were significantly lower in the ibuprofen-treated animals. Neutropenia and thrombocytopenia were not prevented by treatment with ibuprofen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1658896&dopt=Abstract ibuprofen Motrin



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The site of inversion of R(-)-ibuprofen: studies using rat in-situ isolated perfused intestine/liver preparations.

Jeffrey P, Tucker GT, Bye A, Crewe HK, Wright PA.

Department of Medicine and Pharmacology, University of Sheffield, Royal Hallamshire Hospital, UK.

The site of metabolic inversion of R(-)-ibuprofen to the pharmacologically active S(+)-enantiomer has been investigated using an array of in-situ rat perfused organ preparations allowing vascular perfusion (55-60 min) of the separate or combined intestine and liver. After addition of R(-)-ibuprofen (20 mg kg-1 body weight) to the closed (static) lumen of isolated 25 cm lengths of duodenum, jejunum or ileum, and single-pass vascular perfusion, both isomers were measured in the lumen and in vascular perfusate plasma (mean plasma AUC values (+/- s.d., micrograms mL-1 min, n = 5) R(-)-ibuprofen: 1669 +/- 115 (duodenum), 1687 +/- 203 (jejunum), 2061 +/- 188 (ileum); S(+)-ibuprofen: 23 +/- 6 (duodenum), 14 +/- 5 (jejunum), 26 +/- 1 (ileum]. Addition of the same dose of S(+)-ibuprofen to the jejunum (n = 5) resulted in AUC values of 1864 +/- 238 for S(+)-ibuprofen and 6 +/- 3 for R(-)-ibuprofen. After addition of R(-)-ibuprofen (30 micrograms mL-1) to the recirculating vascular perfusate (100 mL) of the entire small intestine (n = 6) AUC values were 1647 +/- 34 for R(-)-ibuprofen and 13 +/- 3 for S(-)-ibuprofen. The same dose of R(-)-ibuprofen to combined intestine/liver (n = 6) and liver only preparations (n = 6) gave AUC values of 1011 +/- 25 and 1021 +/- 49 for R(-)-ibuprofen and 220 +/- 28 and 238 +/- 22 for S(+)-ibuprofen, respectively. In all experiments, except those involving perfusion of the combined intestine/liver and the liver, the concentrations of the isomer opposite to that administered could be accounted for solely by the level of enantiomeric impurity (1.3% for R(-)-ibuprofen and 0.6% for S(+)-ibuprofen). We conclude that inversion of R(-)-ibuprofen to the S(+) antipode occurs in the liver but does not occur on either mucosal or serosal sides of the small intestine of the rat.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1682447&dopt=Abstract ibuprofen Motrin