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Effects of ibuprofen on postoperative bowel motility and propulsion.

Thayer ML, Bubrick MP, Jacobs DM, Frykman S.

Department of Surgery, Hennepin County Medical Center, Minneapolis, Minnesota 55415.

Eighteen mongrel dogs were randomized into two groups, and all underwent right segmental colectomy. One group received ibuprofen, 12 mg/kg, preoperatively and postoperatively q6h for 24 hours; the second group served as a saline control. Propulsion was measured radiographically (q8h X 24h, then q12h) by following intraluminal radiopaque markers. Motility was measured with a multilumen monometric catheter on postoperative days 1, 2, and 3 for a 3-hour period. Propulsion, as defined by movement of more than 80 percent of the markers to the rectum, averaged 46 hours in the saline animals vs. 40.8 hours in the ibuprofen animals for an average decrease of 13 percent (P = .42). Postoperative motility showed a significant increase in the ibuprofen-treated animals on the first postoperative day (26.8 percent, P = .043), most marked at the level of the ileum (48 percent, P = .005), with insignificant differences on the second and third days. Studies comparing ileum, proximal, and distal colon suggest that ileum and proximal colon may be the major site of ibuprofen effect (10.7 percent, P = .23 and 11.96 percent, P = .41 respectively). The data suggest that ibuprofen may have a beneficial effect on postoperative bowel motility but the clinical significance of this still needs to be determined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3366035&dopt=Abstract ibuprofen Motrin



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Effect of ibuprofen on tumor growth in the C6 spheroid implantation glioma model.

Farrell CL, Megyesi J, Del Maestro RF.

Department of Clinical Neurological Sciences, University of Western Ontario, Victoria Hospital, London, Canada.

The effects of long-term low- and high-dose ibuprofen on tumor growth and permeability were assessed in a glioma model in rats. The rats were treated with ibuprofen (24 mg/kg/day or 96 mg/kg/day) for 24 hours before implantation of C6 astrocytoma spheroids and then for 13 days following implantation. The wet and dry weight of the tumors and protein extravasation were measured by an Evans blue dye technique. Protein extravasation did not appear to be reduced by the treatments when assessed on the basis of tumor dry weight. The treatment significantly reduced the wet weight of the tumors in rats treated with high-dose and low-dose ibuprofen when compared to tumor wet weights in untreated rats. High-dose ibuprofen treatment significantly decreased the dry weight of the tumors compared to that of tumors in untreated control animals. It is hypothesized that the ibuprofen treatment regimen employed inhibits prostaglandin-associated angiogenesis induced by the C6 tumor cell growth and/or the implantation technique, thereby interfering with the ability of the tumors to grow.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3373288&dopt=Abstract ibuprofen Motrin



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Differential in vivo effects of indomethacin, ibuprofen, and flurbiprofen on oxygen-dependent killing activities of neutrophils elicited by acute nonimmune inflammation in the rat.

Perianin A, Giroud JP, Hakim J.

Departement de Pathopharmacologie, CNRS U.A. 595, C.H.U. Cochin Port-Royal, Paris, France.

The effects of oral administration of various doses of indomethacin, ibuprofen, and flurbiprofen were studied in acute nonimmune pleurisy induced by calcium pyrophosphate crystals (CaPP) in the rat. Drug effects on pleurisy development, as measured by the pleural fluid volume, the number of emigrating leukocytes, and the in vitro oxygen uptake and hydrogen peroxide production of elicited polymorphonuclear neutrophils (PMNs) were investigated. Indomethacin (1.5, 3, and 6 mg/kg) induced a dose-dependent reduction of both exudate volume and number of emigrating leukocytes which reached approximately 50% of control values. A similar inhibition of these two inflammation parameters was observed for the three doses of ibuprofen (6, 18, and 54 mg/kg) and flurbiprofen (0.5, 1.5, and 4.5 mg/kg). The ability of elicited neutrophils to consume oxygen upon stimulation by serum-treated zymosan particles (STZ) was not altered in PMNs derived from animals treated with indomethacin or flurbiprofen, whereas a 35% decrease was induced by ibuprofen. Ibuprofen, but not indomethacin or flurbiprofen, also impaired STZ-induced PMN production of hydrogen peroxide. Furthermore, this inhibition was inversely related to ibuprofen doses. These data indicate that, in addition to their common properties to reduce leukocyte emigration at inflammatory sites, certain NSAIDs such as ibuprofen, but not flurbiprofen or indomethacin, impair particle-induced oxygen-dependent killing activities of elicited PMNs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3391685&dopt=Abstract ibuprofen Motrin



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Effect of naloxone and ibuprofen on organ blood flow during endotoxic shock in pig.

Nishijima MK, Breslow MJ, Miller CF, Traystman RJ.

Department of Anesthesiology, Johns Hopkins Hospital, Baltimore, Maryland 21205.

The effects of an opiate antagonist naloxone and a cyclooxygenase inhibitor ibuprofen on organ blood flow during endotoxic shock were evaluated in a fluid-resuscitated porcine endotoxic shock model. Radiolabeled microspheres were used to measure regional blood flow. Escherichia coli endotoxin (0.1 mg/kg), infused intravenously over 40 min, reduced mean arterial blood pressure to 50 mmHg and systemic vascular resistance to 57% of control without affecting cardiac output. Endotoxin reduced blood flow to cerebrum (to 49% of control), kidney (to 25% of control), spleen, and skeletal muscle, while blood flow to left ventricle, stomach, and small and large intestines were unaffected. Sixty minutes after endotoxin administration, animals were randomized to one of three groups. Group I animals were controls and received no drug, group II animals received ibuprofen (12.5 mg/kg iv), and group III animals received naloxone (2 mg/kg iv) 60 min after endotoxin. Ibuprofen increased mean arterial blood pressure to 80 mmHg and increased blood flow to both cerebrum (to 92% of control) and kidney (to 47% of control). Plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha were increased 8- and 16-fold, respectively, after endotoxin, and both were decreased by ibuprofen. Naloxone increased mean arterial blood pressure to 62 mmHg but had no effect on regional blood flow or plasma cyclooxygenase metabolite levels. These data suggest that cyclooxygenase metabolites may contribute to decreased mean arterial blood pressure and reduced organ blood flow during endotoxic shock in the pig.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3394818&dopt=Abstract ibuprofen Motrin



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The relationship between plasma ibuprofen concentrations and toxicity in acute ibuprofen overdose.

Jenkinson ML, Fitzpatrick R, Streete PJ, Volans GN.

Department of Rheumatology, Guy's Hospital, London, UK.

1. The information available from the literature and from a prospective survey of ibuprofen overdose being undertaken by the London centre of the National Poisons Information Service (NPIS) was examined utilizing the Generalized Linear Interactive Modelling (GLIM) statistical computing package. 2. This confirmed that timed ibuprofen plasma concentrations were related to the symptoms of tachycardia, dizziness, tinnitus, ocular symptoms and coma/stupor as well as to reversible renal impairment and plasma hepatic enzyme elevation. 3. The best model of the relationship between symptomatic toxicity and timed ibuprofen plasma concentrations, was an exponential equation in time. Because of the lack of specificity or sensitivity in this model, and absence of demonstrable clinical advantages from its application, we do not recommend its use as a guide to predict toxicity. 4. However analysis of a larger information base utilizing similar methodology could, by increasing the statistical power of the resultant model, provide a useful means of predicting ibuprofen toxicity. 5. A previously postulated relationship between post-ingestion ibuprofen plasma concentrations and toxicity was not confirmed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3410480&dopt=Abstract ibuprofen Motrin



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Effect of ibuprofen on gross pathology, bacterial count, and levels of prostaglandin E2 in experimental staphylococcal osteomyelitis.

Rissing JP, Buxton TB.

Infections with Staphylococcus aureus were induced in rat tibiae without sclerosing agents. Animals received ibuprofen or 0.9% NaCl. Both ibuprofen-treated and control animals developed a progressively more-destructive disease over 12 days. Gross tibial pathology was significantly reduced in animals receiving ibuprofen for both six and 12 days postinfection. Radiographic evidence of osteomyelitis was attenuated at 12 days. Geometric mean counts of S. aureus were, however, not significantly changed by ibuprofen treatment. Mean levels of prostaglandin E2 (PGE2) were highest in untreated controls. Ibuprofen treatment of infected animals was associated with a much-reduced mean value of PGE2. Ibuprofen-treated infected tibiae disclosed less PGE2 than did either ibuprofen- or NaCl-treated uninfected tibiae.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3462264&dopt=Abstract ibuprofen Motrin



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Prevention of postsurgical tissue adhesion by anti-inflammatory drug-loaded pluronic mixtures with sol-gel transition behavior.

Oh SH, Kim JK, Song KS, Noh SM, Ghil SH, Yuk SH, Lee JH.

Department of Polymer Science and Engineering, Hannam University, 133 Ojeong Dong, Daedeog Gu, Daejeon 306-791, Korea.

Sol-gel transition temperature-controllable Pluronic F127/F68 mixtures including mildly crosslinked alginate and nonsteroidal anti-inflammatory drug (ibuprofen) were prepared to evaluate their potential as tissue adhesion barrier gels. The sol-gel transition temperatures of the Pluronic mixtures could be controlled by adjusting F127/F68 ratio and polymer concentration. The mildly crosslinked alginate with still flow property provided the residence stability of Pluronic mixture gels in the body. Ibuprofen was loaded in Pluronic mixtures to reduce inflammatory response in the body and, thus, to prevent tissue adhesion. The gelation temperatures of the Pluronic mixtures were not affected by the alginate but lowered by the addition of ibuprofen. The in vitro drug release behavior and in vivo peritoneal tissue adhesion of the Pluronic mixtures with the sol-gel transition just below body temperatures were investigated. The drug release behavior from the ibuprofen (1 wt%)-loaded Pluronic mixture gels at 37 degrees C was examined using a membrane-less dissolution model. The drug in the mixture gels was released continuously up to about 45-65% of the total loading amount during the first 7 days. For in vivo evaluation of tissue anti-adhesion potential, the Pluronic mixtures with/without drug were coated on the peritoneal wall defects of rats and their tissue adhesion extents and tissue reactions (inflammatory response, granulation tissue formation, and toxicity in organs) were compared. It was observed that ibuprofen has a positive effect for the peritoneal tissue anti-adhesion. The Pluronic F127/F68/alginate/ibuprofen mixture gel (25 wt% of F127/F68 [7/3], 1 wt% ibuprofen) was highly effective for the prevention of peritoneal tissue adhesion and showed a relatively low inflammatory response and non-toxicity, and thus can be a good candidate material as a coatable or injectable tissue adhesion barrier gel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15654699&dopt=Abstract ibuprofen Motrin



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Prostacyclin and thromboxane in acute hemorrhagic pancreatitis in dogs.

Kiviniemi H, Ramo J, Stahlberg M, Laitinen S, Jalovaara P, Viinikka L, Kairaluoma M.

To study the role of the vasodilatory, antiaggregatory prostacyclin (PGI2) and its endogenous antagonist thromboxane A2 (TxA2) in acute pancreatitis, we measured serum thromboxane B2 (TxB2, which indicates platelet TxA2 production) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, which indicates systemic PGI2 production) from sequential blood samples in trypsin and taurocholate induced acute canine hemorrhagic pancreatitis (AHP). In addition the effect of a prostaglandin synthesis inhibitor, ibuprofen, was studied and systemic (MAP) and pulmonary artery pressure (MPAP) were recorded for 4.5 hr. The animals were divided into a sham-operated group, an AHP group, an ibuprofen prophylaxis group, and an ibuprofen therapy group. In the sham group the parameters remained stable throughout the experiment. In the AHP group MAP decreased steadily and 6-keto-PGF1 alpha rose significantly from 80.0 +/- 7.8 to 956.0 +/- 287.0 pg/ml (P less than 0.001), whereas serum TxB2 and MPAP remained unchanged. Ibuprofen prophylaxis eliminated the initial fall in MAP and the rise of 6-keto-PGF1 alpha. Ibuprofen therapy normalized the initially decreased MAP and depressed the level of 6-keto-PGF1 alpha. We conclude that PGI2 may at least partly mediate the initial hypotension in canine AHP, whereas platelet TxA2 production obviously has a negligible role in the development of hemodynamic changes in AHP.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3546938&dopt=Abstract ibuprofen Motrin