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Ibuprofen inhibits leukocyte migration through endothelial cell monolayers.

Hofbauer R, Speiser W, Kapiotis S.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria. roland.hofbauer akh-wien.ac.at

During inflammation leukocytes are playing a tremendous role in the defense against bacterial infections. Tumor necrosis factor alpha (TNF alpha) increases adhesion of leukocytes to endothelial cells. The non steroidal anti-inflammatory drug ibuprofen is able to reduce inflammatory processes in humans and is a widely used drug. The influence of ibuprofen on TNF-alpha-induced expression of adhesion molecules on endothelial cells is well investigated and has been published recently by our group. For leukocyte migration, leukocytes have to attach and finally migrate through monolayers of endothelial cells. The aim of the current study was to investigate leukocyte migration through endothelial cell monolayers (ECM) under ibuprofen using a migration assay system. Ibuprofen was identified as a potent inhibitor of the leukocyte migration through endothelial cell monolayers in a dose dependent manner. The treatment of either leukocytes (87 +/- 17.6 %; p>0.05) or endothelial cell monolayers (62.5 +/- 9.4 %; p<0.05) showed that the influence is more mediated through endothelial cells, the treatment of both cell types demonstrated an additive effect. In conclusion, the previously published changes of adhesion molecules on endothelial cells could be confirmed with this functional migration test. The inhibition of the leukocyte migration may contribute to the anti-inflammatory actions of the drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9585108&dopt=Abstract ibuprofen Motrin



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[Effects of amniotic fluid embolism-like plasma on isolated perfused rabbit lungs]

[Article in Chinese]

Yu Y, Jin Z, Bahrami S.

Nanfang Hospital, First Military Medical University, Guangzhou.

OBJECTIVE: In order to investigate whether amniotic fluid could induce the release of mediators from blood cells which would damage the lungs, an isolated perfused rabbit lung (IPRL) was exposed to amniotic fluid embolism-like plasma (AFEP) and the injury of AFEP to lungs and the protective effects of ibuprofen were studied. METHODS: 10 ml human amniotic fluid and 50 ml heparized rabbit blood were incubated together with or without ibuprofen (600 micrograms) at 37 degrees C for 30 min and centrifuged. Supernatants were taken and were referred to as AFEP or ibuprofen AFEP. IPRL was perfused with AFEP, ibuprofen AFEP, simple amniotic fluid (SAF), supernatant of amniotic fluid (SnAF), rabbit plasma (RP) and control NS. The changes of pulmonary artery pressure (PAP), respiratory pressure (RP) and lung weight were recorded by computer and compared with control NS group. RESULTS: In groups of SAF, SnAF and RP PAPs were slightly elevated (0.13-0.6 kPa, P > 0.05), and lung weights were not changed. AFEP induced the increase of PAP (3.52 +/- 0.64 kPa, P < 0.05) and lung weight (4.0 +/- 1.0 g, P < 0.01) with the development of lung edema. Administration of ibuprofen prevented partially the APEP-induced increase of PAP (1.87 +/- 0.43 kPa, P < 0.05) and lung weight (0.4 +/- 0.3 g, P < 0.01). CONCLUSION: Amniotic fluid may induce the release of mediators from blood cells, and the latter is the important cause resulting in the pathological changes of lungs in amniotic fluid embolism. Ibuprofen may reduce partially the APEP-induced lung injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9596884&dopt=Abstract ibuprofen Motrin



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Evidence that ibuprofen antagonizes selective actions of estrogen and tamoxifen on rat bone.

Sibonga JD, Bell NH, Turner RT.

Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA.

Studies were performed to determine if the nonsteroidal anti-inflammatory drug ibuprofen alters bone and mineral metabolism in female rats. In experiment 1, four groups of growing rats underwent either sham operation or ovariectomy (OVX). One week later, controlled-release pellets with ibuprofen or placebo were implanted subcutaneously at the back of the neck. Following 3 weeks of treatment, rats were sacrificed and blood and bone samples were removed for serum assays and histomorphometric analysis. Body growth rate and the static cortical bone measurements made at the tibial diaphysis did not change in response to OVX. OVX, however, did increase radial bone growth, lowered serum 17beta-estradiol, reduced uterine weight, and decreased the cancellous bone area of the tibial metaphysis in the rats. Ibuprofen did not alter serum 17beta-estradiol or uterine weight but reduced radial bone growth as well as cancellous bone area of the tibial metaphysis in both sham-operated and OVX animals. In experiments 2 and 3, we tested the influence of ibuprofen on the effects of the tissue-selective estrogen agonist tamoxifen and of exogenous 17beta-estradiol in the OVX rat. Ibuprofen completely blocked the effects of tamoxifen and partially blocked the effects of 17beta-estradiol to prevent cancellous osteopenia. In contrast, ibuprofen did not influence the effects of tamoxifen and 17beta-estradiol to reduce radial bone growth. Besides the skeletal effects, ibuprofen suppressed estrogen-induced uterine growth. Our data suggest that ibuprofen blocks selective estrogen receptor-mediated activities in the rat.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9610751&dopt=Abstract ibuprofen Motrin



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Altered systemic organ blood flow after combined injury with burn and smoke inhalation.

Sakurai H, Traber LD, Traber DL.

Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Institute, Galveston 77555-0833, USA.

Systemic organ blood flow was longitudinally determined with fluorescent microspheres after severe thermal injury in unanesthetized sheep. After chronic instrumentation, 20 sheep were subjected to combined injury with 40% body surface area third-degree burn and 48 breaths of cotton smoke insufflation. During the next 72 h of the experimental period, all animals were resuscitated with Ringer's lactate following the Parkland formula. To test the effect of systemic administration of ibuprofen, animals were assigned to the control group (n=11) or the ibuprofen group (n=9). In the ibuprofen group, animals received ibuprofen as a 12 mg/kg bolus injection 1 h after injury and 6 mg/kg/h as a continuous infusion for the next 47 h. After this combined injury, animals exhibited a biphasic hemodynamic alteration, with an initial shock period and a later hyperdynamic period, a phenomenon often seen in severely burned patients. Among multiple organs, the splanchnic organs exhibited more dominant and sustained decreases in regional blood flow, whereas heart and kidney blood flow were maintained at more than 90% of baseline level even in the initial hypovolemic phase. In the postresuscitation period, no organ except the heart showed increased regional blood flow, despite a more than 20% increase in cardiac output. Ibuprofen had effects on early recovery from the initial shock period, and it improved intestinal organ blood flow, suggesting a potential benefit of this drug for severe thermal injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9617888&dopt=Abstract ibuprofen Motrin



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Role of nitric oxide and cyclooxygenase products in controlling vascular tone in uterine microvessels of rats.

Saha PR, Alsip NL, Henzel MK, Asher EF.

Center for Applied Microcirculatory Research, University of Louisville, School of Medicine, KY 40292, USA.

The importance of nitric oxide (NO) and dilator prostaglandins in uterine resistance arterioles was investigated. In pentobarbital anaesthetized rats at dioestrus-2, the uterine microcirculation in vivo was transilluminated by a fibreoptic probe and microvessels (circumferential arterioles) viewed by video microscopy. Arteriolar diameters were measured while increasing concentrations of acetylcholine (ACh), serotonin (5-HT), phenylephrine (PE), or angiotensin II (AII) were applied topically (suffused) over the uterus. Agonists were applied alone or with ibuprofen (IBU; cyclooxygenase inhibitor), N omega-nitro-L-arginine (L-NA; nitric oxide synthase inhibitor) or both. Circumferential arterioles were dilated by ACh and 5-HT (10(-8)-10(-4) mol l-1) and constricted by PE (10(-8)-10(-5) mol l-1) and AII (10(-11)-10(-7) mol l-1). Suffusion of L-NA or L-NA with ibuprofen (10(-4) mol l-1 each) abolished ACh-induced dilation; ibuprofen alone blocked dilation at higher ACh concentrations. Serotonin-induced relaxation was significantly attenuated by L-NA alone or in combination with ibuprofen. Vasoconstriction induced by PE was enhanced by L-NA alone and L-NA with ibuprofen, but ibuprofen alone had no effect. In contrast, AII-induced constriction was enhanced significantly by ibuprofen or L-NA and further enhanced when both ibuprofen and L-NA were present. These results suggest that ACh can release either nitric oxide (NO) or cyclooxygenase products to cause uterine arteriolar dilation and that 5-HT-induced uterine microvascular relaxation is mediated via NO only. They also suggest that PE-induced vasoconstriction is attenuated by the release of NO but not cyclooxygenase products and that constrictor responses evoked by AII are attenuated by both NO and dilator prostaglandin release. Thus, both nitric oxide and dilator prostaglandins are important in the control of uterine microvessels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9640259&dopt=Abstract ibuprofen Motrin



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A case-control study of acute ibuprofen toxicity in dogs.

Poortinga EW, Hungerford LL.

Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign 61801, USA. epoortin acr.acfac.rpslmc.edu

A case-control study used data in the National Animal Poison Control Center database to characterize risk factors for gastrointestinal ulceration and acute renal failure subsequent to the acute ingestion of ibuprofen in the dog. For gastrointestinal ulceration (GIU) subsequent to ibuprofen ingestion, four factors differentiated the 116 cases from the 93 controls. Risk of GIU was lower for dogs where the time from ingestion to intervention was known as opposed to missing (adjusted odds ratio (aOR) = 0.12, p = 0.0001). Risk of GIU was also lower for the Labrador breed (aOR = 0.22, p = 0.004). Risk of GIU was higher for each unit of the logarithm of time to intervention (aOR = 2.63, p = 0.0002) and for the German Shepherd breed (aOR = 5.67, p = 0.14). For acute renal failure (ARF) subsequent to ibuprofen ingestion, two factors differentiated the 80 cases from the 64 controls. Risk of ARF was lower for dogs where the time from ingestion to intervention was known as opposed to missing (aOR = 0.15, p = 0.0001). Risk of ARF was higher for each unit of the logarithm of time to intervention (aOR = 2.16, p = 0.01). Although this study failed to describe a dose-response relationship, it appears that there are significant breed differences in susceptibility to GIU subsequent to ibuprofen exposure. Time to intervention was critical for both GIU and ARF outcomes. Dogs, particularly German Shepherds, ingesting even small amounts of ibuprofen, may need to be managed aggressively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9646335&dopt=Abstract ibuprofen Motrin



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Ibuprofen affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients.

Chang SH, Chung JG, Huang LJ, Chen SC, Kuo SC.

Department of Medicine, China Medical College, Taichung, Taiwan, Republic of China.

Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene and p-aminobenzoic acid were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without specific concentrations of ibuprofen co-treatment showed different percentages of 2-aminofluorene and p-aminobenzoic acid acetylation. The data indicate that there was decreased NAT activity associated with increased levels of ibuprofen in H. pylori cytosols. Inhibition of growth studies on H. pylori demonstrated that ibuprofen elicited a dose-dependent bactericide effect in H. pylori cultures, i.e. the greater the concentration of ibuprofen, the greater the inhibition of growth to H. pylori. For the cytosol and intact bacteria examinations, the apparent values of Km and Vmax were decreased after co-treatment with 40 microM ibuprofen. This report is the first demonstration of ibuprofen inhibition of arylamine N-acetyltransferase activity and ibuprofen inhibition of growth in the bacterium H. pylori.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9685046&dopt=Abstract ibuprofen Motrin