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Query: UMLS:C0850803 (anaphylaxis)
 8,092 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thromboxanes (Txs) were implicated as possible participants in the altered microvascular permeability of acute lung injury when the Tx synthase inhibitor, OKY-046, was reported to prevent pulmonary edema induced by phorbol myristate acetate (PMA). Recently, however, we found that OKY-046, at a dose just sufficient to block Tx synthesis in intact dogs, did not prevent PMA-induced pulmonary edema but rather merely reduced it modestly. The present study was designed to explore other mechanisms whereby OKY-046 might prevent PMA-induced pulmonary edema. The finding that 5-lipoxygenase (5-LO) metabolites of arachidonic acid were increased within the lung after PMA administration, coupled with the report that OKY-046 inhibited slow-reacting substance of anaphylaxis formation, permitted formulation of the hypothesis that OKY-046, at a dose in excess of that required to inhibit Tx synthesis, inhibits the formation of a product(s) of 5-LO and, thereby, prevents edema formation. In vehicle-pretreated pentobarbital-anesthetized male mongrel dogs (n = 4), PMA (20 micrograms/kg i.v.) increased pulmonary vascular resistance (PVR) from 4.4 +/- 0.3 to 26.3 +/- 8.8 mmHg.l-1 x min (P < 0.01) and extravascular lung water from 6.7 +/- 0.5 to 19.1 +/- 6.2 ml/kg body wt (P < 0.05). Concomitantly, both TxB2 and leukotriene B4 (LTB4) were significantly increased in the lung. Pretreatment with OKY-046 (100 mg/kg i.v., n = 8) prevented PMA-induced increases in TxB2, LTB4, and pulmonary edema formation but did not prevent the increase in PVR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:OKY-046 prevents increases in LTB4 and pulmonary edema in phorbol ester-induced lung injury in dogs. 133 76

During anaphylaxis the sensitized liver can have substantial capacity for leukotriene production. However, the intrahepatic cellular source for these potent eicosanoid mediators has been unclear so far. We therefore analyzed the appropriate role of resident liver cells in organ-specific generation of leukotrienes by immunohistochemical localization of 5-lipoxygenase, by measurement of cysteinyl leukotriene production in animals or isolated livers and by histochemical monitoring of mast cells in rat, guinea pig and mouse livers, respectively. During anaphylaxis in vivo, these species all generated large amounts of leukotrienes. Immunohistochemistry with rat liver demonstrated resident mast cells as the predominant cell type in liver containing 5-lipoxygenase. Rat and guinea pig livers contained numerous mast cells and produced substantial amounts of leukotrienes on antigen challenge; in contrast, mouse livers neither showed detectable mast cells nor generated leukotrienes when stimulated analogously. Infusion of histamine or serotonin (1 mmol/L each) or of the degranulating substance P (8 mumol/L) did not elicit leukotriene generation in rat livers. Furthermore, substantial degranulation of liver mast cells by compound 48/80 (0.5 mg/kg body mass) was paralleled by only modest leukotriene formation (63 +/- 10 pmol in bile/kg body mass/30 min). These results indicate that during anaphylaxis mast cells are the main intrahepatic cells initiating leukotriene production and that such leukotriene generation is likely to be independent of mast cell degranulation or the release of histamine or serotonin.
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PMID:Resident mast cells are the main initiators of anaphylactic leukotriene production in the liver. 144

Airway damage secondary to eosinophil activation is thought to contribute to the development of asthma. Using the fluorescent dye FURA-2 to measure the concentration of cytosolic calcium, we found that supernatants from anti-IgE-stimulated human lung mast cells increased cytosolic calcium in human eosinophils. We then examined the major mast cell mediators (histamine, PGD2, platelet-activating factor (PAF), eosinophil chemotactic factor of anaphylaxis (ECF-A), leukotriene (LT)C4 and LTB4) for their ability to increase cytosolic calcium in eosinophils. We found that both PAF (5 x 10(-9) to 5 x 10(-6) M) and PGD2 (two of five donors responsive at 1 x 10(-9) M) were potent stimuli for calcium mobilization. LTB4 (10(-8), 10(-7) M) and histamine were also active, although higher concentrations of histamine were required to see a response (3 x 10(-7) to 10(-5) M). LTC4, val-ECF-A, and ala-ECF-A were inactive. The effects of PGD2 and histamine were specific for eosinophils, although LTB4 and PAF increased calcium in both neutrophils and eosinophils. The histamine-induced increase in intracellular calcium was not blocked by the H1 or H2 antagonists pyrilamine or cimetidine (10(-4) M), respectively; however, the response to 10(-6) M histamine was completely blocked by the specific H3 antagonist thioperamide (10(-6) M). To evaluate the relative contribution of these stimulatory mast cell mediators on the calcium mobilizing activity in supernatants from anti-IgE-stimulated human lung mast cell (HLMC), we examined the effect of supernatants from HLMC pretreated with indomethacin and/or the 5-lipoxygenase pathway inhibitor MK886. These supernatants were added to FURA-2-loaded eosinophils that had been preincubated with thioperamide and/or the PAF antagonist WEB-2086. We found that the increase in eosinophil calcium in response to supernatants from anti-IgE-stimulated-HLMC was totally inhibited only when the mast cells were challenged in the presence of indomethacin and MK886, and the eosinophils were preincubated with thioperamide. WEB-2086 had little effect. When we examined the effect of these mediators on eosinophil secretory function, we found that PGD2 (not histamine) primed eosinophils for enhanced release of LTC4 in response to the calcium ionophore A23187. We conclude that the activation of eosinophils by PGD2 and other mast cell products may contribute to airways inflammation that is characteristic of asthma.
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PMID:Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. 158 43

The regulation of anaphylaxis-mediated fluid secretion by the small intestine was examined in rats immunized by infection with Trichinella spiralis and reinfected by intraduodenal injection with L1 larvae. Net fluid secretion, which was measured as the volume of fluid present in the intestine 30 minutes after the challenge infection, was significantly greater in both actively and passively immunized rats than in nonimmune rats. The amount of fluid recovered from the immune host was equivalent to that secreted in response to 50 micrograms/kg of prostaglandin E2 or 250 micrograms/kg of cholera toxin. Worm-induced fluid secretion in immune hosts was reduced by treatment with diphenhydramine and inhibited by the dual application of diphenhydramine and indomethacin. Indomethacin alone had no effect despite inhibiting mucosal prostaglandin synthesis. Fluid secretion was unaltered by prior treatment of immune rats with a 5-lipoxygenase inhibitor, L-651,392, and only slightly reduced when L-651,392 was used in combination with indomethacin. After a challenge infection, more histamine was released into intestinal loops of immune rats than those of nonimmune rats. Prechallenge treatment of immune rats with indomethacin caused a twofold increase in histamine release. In summary, anaphylaxis-induced fluid secretion in the small intestine is mediated largely by histamine and cyclooxygenase products. This secretion can be lowered by treatment with diphenhydramine and further reduced by diphenhydramine in combination with indomethacin. The paradoxical effects of indomethacin when used alone and in combination with diphenhydramine are explained by the downregulation of histamine release by products of the cyclooxygenase pathway.
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PMID:Inhibition of anaphylaxis-evoked intestinal fluid secretion by the dual application of an H1 antagonist and cyclooxygenase inhibitor. 170 7

The response to antigen (trinitro-phenyl-haptenized ovalbumin) and the modulatory role of several antiallergic drugs was studied in isolated hearts from actively sensitized rats. Antigen induced a triphasic effect on coronary flow (CF) and left ventricular pressure (LVP) characterized by short-term increase (0-1.5 min = phase 1) and a severe decrease (1.5-7.5 min = phase 2) followed by a less pronounced long-lasting decrease (7.5- greater than 20 min = phase 3). The first phase was accompanied with a substantial release of 5-hydroxytryptamine (5-HT), histamine, and leukotrienes measured in cardiac effluents. The histamine2 (H2)-receptor antagonist cimetidine (60 microM) reversed the antigen-induced increase in CF to a decrease. In contrast, H1-receptor blockade by mepyramine (6 microM) had no effect. Methysergide (10 microM) and ketotifen (0.1 microM) evoked a mild suppression during all three phases. Indomethacin (10 microM) was almost inactive while tolfenamic acid (1 microM) was slightly active in this respect during phase 2. Addition of the 5-lipoxygenase inhibitor AA 861 (1 microM) resulted in complete suppression of the antigen-induced decrease in CF. The leukotriene antagonist FPL 55712 (5 and 50 nM) evoked a dose-dependent suppression with respect to the anaphylactic phases 2 and 3. A similar reduction was obtained with sodium cromoglycate (1 mM). AA 861, FPL 55712, and sodium cromoglycate also suppressed the antigen-induced decrease in LVP. The antigen-induced histamine release was not affected by the aforementioned drugs. Our results provide evidence that H2-receptor blockade during cardiac anaphylaxis enhances coronary constriction and may be detrimental in this condition. On the other hand, leukotriene antagonists and 5-lipoxygenase inhibitors may exert beneficial effects during cardiac anaphylaxis. Further experiments in this area are needed to clarify the precise role of mast cell-generated mediators in cardiac anaphylaxis possibly leading to new therapeutic approaches in this life-threatening disorder.
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PMID:Characterization and modulation of antigen-induced effects in isolated rat heart. 172 33

This study investigated the role of phospholipid-derived inflammatory mediators in electrolyte transport in the normal rat jejunum and during intestinal anaphylaxis to a food protein in a rat model. In a standard Ussing chamber preparation, the leukotrienes (LTs) C4 and D4 both significantly stimulated an increase in short-circuit current in a concentration-dependent manner. The responses to both LTC4 and LTD4 were significantly reduced by the LTD4 receptor antagonist, MK-571. The 5-lipoxygenase products, LTB4, 5-hydroxyeicosatetraenoic acid and 5-hydroperoxyeicosatetraenoic acid did not significantly alter short-circuit current. The thromboxane mimetic, U-46619, had a small, but significant stimulatory effect on short-circuit current. Platelet-activating factor (PAF) caused a significant, concentration-dependent increase in short-circuit current, with effects at concentrations as low as 2 nM and with a maximum effect of 69 +/- 14 microA/cm2. The stimulatory effect of 0.2 microM PAF was significantly reduced by the PAF receptor antagonist WEB 2086. Exposure of sensitized jejunum to ovalbumin caused a biphasic increase in short-circuit current which was reduced by pretreatment with the 5-lipoxygenase inhibitor, L651,392, and the PAF receptor antagonist, WEB 2086. The response to ovalbumin was not significantly affected by pretreatment of the tissue with the LTD4 receptor antagonist, MK-571, at concentrations which inhibited the responses to exogenous LTC4 and LTD4. The thromboxane/endoperoxide receptor antagonist, L670,596, had no significant effect on the short-circuit current response to ovalbumin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A role for phospholipid-derived inflammatory mediators in intestinal anaphylaxis in the rat. 173 23

To determine whether the release of newly formed mediators such as the peptidoleukotrienes and platelet-activating factor might modulate the food protein induced jejunal smooth muscle contraction observed in sensitized rats, Hooded-Lister rats were sensitized by injection of ovalbumin (10 micrograms i.p.) and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally (n = 9) and circularly (n = 9) oriented jejunal segments (mucosa intact) were examined in standard tissue baths in response to antigen, leukotrienes, and platelet-activating factor alone and in the presence of a specific leukotriene receptor antagonist (MK-571), a 5-lipoxygenase inhibitor (L651,392), and a platelet-activating factor receptor antagonist (WEB 2086). Although the responses of control and sensitized tissues to stretch and 10(-4) M bethanechol were similar, only sensitized tissues contracted in response to antigen (1 mg/mL). MK-571 (10(-5) M) reduced or significantly inhibited the contractile response of sensitized longitudinally and circularly oriented tissues to 10(-7) M leukotrienes C4, D4, or E4, but neither L651,392 (10(-4) M) nor MK-571 (10(-5) M) significantly reduced the contractile response of sensitized tissues to antigen challenge. WEB 2086 (10(-4) M) significantly (p less than 0.01) reduced the contractile response of sensitized longitudinally and circularly oriented tissues to 10(-7) M platelet-activating factor but did not significantly alter the response to antigen in longitudinally (45% of control, p = 0.14) or circularly (118% of control, ns) oriented jejunal smooth muscle. In this model leukotrienes and platelet-activating factor play an insignificant role in modulating food protein induced jejunal smooth muscle contraction in intestinal anaphylaxis.
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PMID:A limited role for leukotrienes and platelet-activating factor in food protein induced jejunal smooth muscle contraction in sensitized rats. 180 57

In the search for a model of leukotriene (LT) production to provide a method to determine in vivo 5-lipoxygenase (5-LO) inhibitory activity by various compounds, a passive anaphylactic reaction in the rat peritoneal cavity was examined, refined and characterized. The reaction, produced by passive sensitization with an i.p. injection of rabbit anti-bovine serum albumin (anti-BSA) followed by an i.p. injection of BSA, resulted in the biosynthesis of large amounts of sulfidopeptide LTs measurable by immunoassay or by reversed phase high performance liquid chromatography. The oral activity of several 5-LO inhibitors has been examined using this model. An example of these is zileuton (Abbott-64077), a potent 5-lipoxygenase inhibitor now under clinical evaluation. Zileuton inhibited sulfidopeptide LT biosynthesis in the rat peritoneal cavity in a dose-dependent manner (ED50 = 3 mg/kg). WY-49,232, MK-866, BW A4C and phenidone also produced good activity with ED50 values of 6, 8, 11 and 17 mg/kg, respectively. This modified rat peritoneal anaphylaxis model appears to be a valuable tool for establishing in vivo activity of 5-LO inhibitors.
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PMID:Inhibition of leukotriene biosynthesis in the rat peritoneal cavity. 181 62

The leukotrienes constitute a group of 5-lipoxygenase catalyzed metabolites of arachidonic acid, the cellular effects of which may be divided into two broad categories. Leukotriene B4 is predominantly a leukocyte stimulant, and has recently been observed to represent the inflammatory cell component of a mutual activation mechanism between inflammatory cells and the immune system. It is thus anticipated that LTB4 acts as an inflammatory mediator and immune regulator in a variety of immune-mediated disorders. The presence of LTB4 in inflamed tissues from patients with psoriasis, rheumatoid arthritis and chronic inflammatory bowel disease renders it probable that the novel class of 5-lipoxygenase inhibitors and LTB4 antagonists will be capable of influencing the clinical course of these diseases. The other main group is comprised of leukotrienes C4, D4 and E4, collectively known as slow reacting substance of anaphylaxis leukotrienes, and has been identified primarily in immediate hypersensitivity conditions, e.g. bronchial asthma in which the smooth muscle contractile and permeability increasing properties of SRS-A appears to contribute to the early bronchoconstrictor phase. Leukotriene D4, however, may also be involved in the late reaction mediated by inflammatory cells, since it has the ability to immobilize neutrophils attracted by LTB4 to the inflammatory focus. The ultimate elucidation of the importance of leukotrienes in different diseases awaits the outcome of clinical trials with the newly developed highly potent and specific 5-lipoxygenase inhibitors and leukotriene antagonists.
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PMID:[Leukotrienes. A review of the significance for disease in man and the possibilities for therapeutic intervention]. 199 35

The effects of alminoprofen, a nonsteroidal anti-inflammatory agent, on the experimental animal models of allergic reactions were examined and compared with those of ibuprofen. Alminoprofen at 30 mg/kg given intraduodenally significantly suppressed passive anaphylactic bronchoconstrictions, while ibuprofen did not at the same doses. In vitro studies revealed that alminoprofen, in contrast to ibuprofen, exerted an inhibitory effect on arachidonate 5-lipoxygenase activity which initiates the bio-synthesis of leukotrienes. Alminoprofen inhibited arachidonic acid-induced ear edema in mice and homologous passive cutaneous anaphylaxis in rats at high doses, while ibuprofen did not at the high doses. From its characteristic feature of inhibitory effects on 5-lipoxygenase activity and the experimental model of type I allergic reaction, it is suggested that alminoprofen is a new type of nonsteroidal anti-inflammatory agent.
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PMID:[Effects of alminoprofen on the allergic reactions]. 207 51


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