leukotriene-b4 and Hemorrhage

Exhaled breath condensate (EBC) analysis is a noninvasive method to assess the lower respiratory tract. In human subjects, EBC hydrogen peroxide (H. To determine associations between EBC biomarkers and cytological and endoscopic definitions of lower airway inflammation (LAI) while controlling for sampling and environmental variables.. Prospective, cross-sectional study.. EBC pH and H. LAI is challenging to categorise due to a variety of clinical and cytological phenotypes. Although the study was designed to overcome this limitation, numbers of horses were small in some categories.

Topics: Analysis of Variance; Animals; Biomarkers; Breath Tests; Bronchoalveolar Lavage Fluid; Bronchoscopy; Cross-Sectional Studies; Eosinophils; Female; Hemorrhage; Horse Diseases; Horses; Hydrogen Peroxide; Hydrogen-Ion Concentration; Inflammation; Leukotriene B4; Linear Models; Male; Multivariate Analysis; Neutrophils; Prospective Studies; Respiratory System; Respiratory Tract Diseases

The blood-gas barrier must be very thin to allow gas exchange and it is therefore subjected to high mechanical stresses when the capillary pressure rises. In some animals, such as the thoroughbred race-horse during intense exercise, the stresses are so large that the capillaries fail and bleeding occurs. We tested the hypothesis that, in elite human athletes, the high capillary pressure that occurs during severe exercise alters the structure and function of the blood-gas barrier. We performed bronchoalveolar lavage (BAL) in six healthy athletes, who had a history suggestive of lung bleeding, 1 h after a 7-min cycling race simulation and four normal sedentary control subjects who did not exercise before BAL. The athletes had higher (p < 0.05) concentrations of red blood cells (0.51 x 10(5) versus 0.01 x 10(5).ml-1), total protein (128.0 versus 94.1 micrograms/ml), albumin (65.6 versus 53.0 micrograms/ml), and leukotriene B4 (LTB4) (243 versus 0 pg/ml) in BAL fluid than control subjects. The proportion of neutrophils was similar in athletes and control subjects but the proportion of lymphocytes in BAL fluid was reduced (p < 0.05). There were no differences in levels of surfactant apoprotein A, tumor necrosis factor bioactivity, lipopolysaccharide, or interleukin-8 (IL-8) between groups. These results show that brief intense exercise in athletes with a history suggestive of lung bleeding alters blood-gas barrier function resulting in higher concentrations of red cells and protein in BAL fluid. The lack of activation of proinflammatory pathways (except LTB4) in the airspaces supports the hypothesis that the mechanism for altered blood-gas barrier function is mechanical stress.

Topics: Adult; Apolipoproteins A; Bronchoalveolar Lavage Fluid; Bronchoscopy; Capillaries; Capillary Permeability; Exercise; Female; Hemorrhage; Humans; Leukotriene B4; Lung; Lung Diseases; Male; Prospective Studies; Pulmonary Gas Exchange; Tumor Necrosis Factor-alpha

Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48/80-induced mouse ear edema was suppressed by YT-1 in a dose-dependent manner. In isolated rat peritoneal mast cells, YT-1 produced a dose-dependent inhibition of bradykinin-, substance P- and compound 48/80-induced histamine and beta-glucuronidase release. YT-1 also reduced the TXB2 formation from PMN leukocytes with IC50 2.0 +/- 0.5 microM, however with little effect on LTB4 formation. Histamine- and serotonin-induced plasma exudation in ear edema were reduced by YT-1. Moreover, the maximal response of ileum contraction caused by histamine and serotonin were also suppressed by YT-1 in a dose-dependent manner. In compound 48/80-pretreatment mice, YT-1 failed to suppress the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These results indicate that the inhibitory effect of YT-1 on local edema formation is not through the release of steroid hormones from adrenal gland, and is probably by suppressing the release of chemical mediators from mast cells, inhibition of prostaglandins formation, and noncompetitive but selective protection of the vasculature against the histamine- and serotonin-induced plasma extravasation.

Topics: Animals; Ear Diseases; Edema; Guinea Pigs; Hemorrhage; Hindlimb; Histamine; Ileum; In Vitro Techniques; Leukotriene B4; Mast Cells; Mice; Mice, Inbred ICR; Muscle Contraction; p-Methoxy-N-methylphenethylamine; Quinolones; Rats; Rats, Sprague-Dawley; Serotonin; Skin; Thromboxane B2

Several studies have reported that prostanoids are involved in many of the physiopathological mechanisms underlying acute pancreatitis but their precise role in this disease remains to be established. The objective of this work is to evaluate the variation of local tissue production of prostanoids and lipoxygenase metabolites of arachidonic acid in acute pancreas inflammation induced by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg body weight) in rats. Pancreatic tissue levels of leukotriene B4 (LTB4), 15 hydroxyeicosatetraenoic acid (15-HETE), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were determined by HPLC-RIA techniques at 5 and 60 minutes after induction of acute pancreatitis (AP). Prostanoids increased significantly at 5 minutes and LTB4 and 15-HETE at 60 minutes. These data confirm that the prostanoid imbalance could be considered as an early specific response of the pancreas to the inflammatory events characteristic of induced AP while the altered levels of the lipoxygenase products (LTB4 and 15-HETE) would be more of a nonspecific organ response associated to the high cellular infiltration rate and necrosis observed in the late phases of acute pancreatitis.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Animals; Dinoprostone; Hemorrhage; Hydroxyeicosatetraenoic Acids; Kinetics; Leukotriene B4; Lipoxygenase; Male; Pancreas; Pancreatitis; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Taurocholic Acid; Thromboxane B2

In the present study we investigated the involvement of lipid mediators in an experimental model of immune-complex alveolitis induced in rat lungs by intrabronchial instillation of rabbit antibodies to ovalbumin followed by i.v. injection of the antigen. It was found that the reaction did not induce detectable oedema, as measured by the dry:wet weight ratio. A marked influx of neutrophils was observed in the bronchoalveolar lavage fluid, progressing from 6 to 24 h in parallel with the development of haemorrhagic lesions in lung parenchyma. The intensity of these lesions, evaluated by the concentration of extravascular haemoglobin, was not significantly affected by pretreatment of the animals with a cyclo-oxygenase inhibitor (indomethacin), a thromboxane inhibitor (econazole) or a thromboxane antagonist (L-655,240). However, the antagonists of platelet activating factor (PAF), WEB-2086 and BN-52021, and the lipoxygenase inhibitors, nor-dihydroguaiaretic acid and L-663,536, all significantly inhibited the haemorrhagic lesions. A peptide leukotriene antagonist (L-660,711) had no effect. Furthermore, the PAF antagonists inhibited the levels of LTB4, but not of PGE2 and thromboxane, released into the bronchoalveolar space 1 h after induction of the reaction. These results suggest that the haemorrhagic lesions in this model of immune-complex alveolitis are mediated by PAF and leukotrienes, possibly LTB4.

Topics: Alveolitis, Extrinsic Allergic; Animals; Azepines; Bronchoalveolar Lavage Fluid; Dinoprostone; Diterpenes; Econazole; Ginkgolides; Hemoglobins; Hemorrhage; Indomethacin; Lactones; Leukotriene B4; Leukotrienes; Lipoxygenase Inhibitors; Male; Platelet Activating Factor; Propionates; Quinolines; Rats; Rats, Inbred Strains; Thromboxanes; Triazoles

1. PAF and LTs may be mediators of the acute gastrointestinal mucosal damage due to endotoxic shock. 2. LTs may be mediators of the acute gastrointestinal mucosal damage due to PAF administration. 3. LMW heparin and unfractionated heparin prevented the increase of LTs due to endotoxin and PAF administration.

Topics: Acute Disease; Animals; Benzoquinones; Dogs; Gastric Mucosa; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Intestinal Mucosa; Leukotriene B4; Lipoxygenase Inhibitors; Necrosis; Phospholipid Ethers; Platelet Activating Factor; Shock, Septic

The relative potencies of platelet-activating factor (PAF), leukotrienes B4 (LTB4), C4 (LTC4), D4 (LTD4) and histamine to induce hemoconcentration (HC) were evaluated in the guinea pig. The maximal hematocrit increase (MHI) from PAF, LTD4 and histamine occurred 5-7 min after i.v. injection, whereas the MHI of LTC4 occurred 13-15 min after injection. LTB4 (2.97-5.95 nmol kg-1) did not produce HC. The magnitude of PAF-induced MHI was 2-fold that of LTC4 or LTD4, regardless of the dose of leukotrienes used. The doses (nmol kg-1) needed to produce 30% HC were: 0.14-PAF, 0.71-LTD4 and 3.37-LTC4 and 2,400 histamine. The HC effects of LTD4 were markedly reduced by prior administration of FPL-55712. However, neither LTC4 or LTD4 HC effects were significantly reduced by prior i.v. injection of CV-3988 (3.4 mg kg-1), a competitive receptor antagonist to PAF which is 98% effective in abolishing HC response to 0.14 nmol kg-1 PAF. Diphenhydramine abolished histamine-induced hemoconcentration but was without effect on PAF or LTD4. These results suggest that the responses of PAF, leukotrienes and histamine differ in their potency and may involve separate vascular recognition sites related to acute increases in vascular permeability.

Topics: Animals; Chromones; Diphenhydramine; Dose-Response Relationship, Drug; Guinea Pigs; Hematocrit; Hemorrhage; Histamine; Injections, Intravenous; Leukotriene B4; Male; Phospholipid Ethers; Plasma; Platelet Activating Factor; SRS-A; Thiazoles; Time Factors

The effect of synthetic leukotriene B4 (LTB4) on chemotaxis in vivo (51Cr-polymorphonuclear leukocyte [PMN] accumulation) was examined and its potency compared with that of C5a des Arg-containing zymosan-activated plasma (ZAP). On a molar basis the amount of C5a des Arg calculated to be in our preparation of ZAP was found to be up to approximately 80 times more potent than LTB4, although in vitro the two chemotaxins have been reported to be about equipotent. ZAP is more representative of what may happen in vivo than its principal constituent C5a des Arg, but for a more precise comparison the purified and isolated peptide will have to be compared with synthetic LTB4. Whereas ZAP induced severe PMN-dependent microvascular injury (increase in vessel permeability [125I-albumin] and hemorrhage [59Fe-erythrocytes]), LTB4 only induced an increase in vascular permeability, and this occurred only in the presence of simultaneously injected prostaglandin E2 (PGE2). PGE2 also enhanced substantially the number of PMNs and the amount of exuded plasma at injection sites of the chemotaxins. However, unlike in two other reports, LTB4 did not cause an immediate transient increase in vessel permeability, nor did it enhance the permeability-increasing effect of bradykinin. Furthermore, unlike PGE2 LTB4 did not induce an increase in blood flow, but a decrease (57Co-microspheres). It is concluded that LTB4 may act as a host-derived chemoattractant in vivo, but, compared with that of ZAP (primarily activated complement), its role in acute inflammation is probably less significant than that of the complement-derived chemotaxin(s).

Topics: Animals; Capillary Permeability; Cell Movement; Chemotactic Factors; Complement C5; Complement C5a, des-Arginine; Dermatitis; Dinoprostone; Female; Hemorrhage; Leukotriene B4; Microcirculation; Neutrophils; Prostaglandins E; Rabbits; Regional Blood Flow; Scintillation Counting; Zymosan