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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of prostacyclin (PGI2) on the airway responses to platelet-activating factor (PAF) in a randomized and crossover study in eight normal subjects. PGI2 or diluent (glycine buffer) was continuously infused on 2 separate days. Two breaths of PAF (21 micrograms) were inhaled three times every 15 minutes and airflow at 30% of vital capacity from partial flow-volume curves (Vp30) was measured. PGI2 (4 ng/kg/min) had no effect on Vp30 or blood pressure, whereas heart rate increased from 70.3 +/- 3.9 to 73.7 +/- 4.0 beats/min (mean +/- SEM; p less than 0.01). Two subjects did not complete the study because of transient hypotension. PGI2 had no effect on PAF-induced bronchoconstriction with maximal decreases in Vp30 of 42.0 +/- 8.0% (p less than 0.01) during PGI2 and 49.8 +/- 14.2% (p less than 0.02) during diluent infusion. Ex vivo platelet aggregation to PAF (10(-9) to 10(-7) mol/L) was significantly inhibited by PGI2. Circulating neutrophils decreased from 4.7 +/- 0.9 x 10(9)/L to 1.5 +/- 0.3 x 10(9)/L (p less than 0.05) 5 minutes after the first PAF inhalation during diluent infusion, whereas there was no significant change with PGI2. Thus, PGI2 does not influence PAF-induced bronchoconstriction in man despite causing marked inhibition of ex vivo PAF-induced platelet aggregation and preventing the fall of neutrophils.
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PMID:Effects of prostacyclin on bronchoconstriction and neutropenia induced by inhaled platelet-activating factor in man. 210 2

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.
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PMID:Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients. 211 86

This study tested the hypothesis that sympathetic neural stimulation increases the prevalence of reperfusion-induced ventricular fibrillation and explored the mechanisms by which this occurs and how it may be prevented. In anesthetized, autonomically denervated dogs, we examined the effects of bilateral ansae subclaviae stimulation (SS) and of induction of pericardial biosynthesis of prostaglandins, an intervention that reduces SS effects by acting at presynaptic sites. A 5-minute occlusion of the left anterior descending coronary artery distal to the first or second diagonal branch was performed during SS. Heart rate was maintained constant by atrial pacing. In the absence of SS, one of 23 dogs developed ventricular fibrillation during occlusion, and three of the remaining 22 dogs developed ventricular fibrillation upon reperfusion. SS did not increase the prevalence of occlusion-induced ventricular fibrillation (four of 23 dogs) but increased the prevalence of reperfusion-induced ventricular fibrillation (12 of the remaining 19 dogs, p = 0.01). SS did not affect occlusion-induced decrease in local electrogram amplitude recorded from the ischemic myocardium or myocardial blood flow to the ischemic myocardium during occlusion or reperfusion. SS, however, prevented occlusion-induced increase in diastolic excitability threshold. Instillation into the pericardial cavity of arachidonic acid solution (3 micrograms/ml) resulted in release of prostacyclin, measured by radioimmunoassay as a stable metabolite 6-ketoprostaglandin F1 alpha (63.1 +/- 11.3 ng/ml, n = 11, mean +/- SEM), and of prostaglandin E2 (7.0 +/- 0.9 ng/ml, n = 11). This pericardial solution blunted SS-induced increase in mean arterial blood pressure and reduced the prevalence of ventricular fibrillation during reperfusion (six dogs to one dog, p less than 0.05). Blood flow to the ischemic myocardium remained unaffected. Indomethacin, when added to the solution (3 micrograms/ml), reversed the effects of prostaglandin release and arrhythmia development. These data indicate that efferent sympathetic stimulation during a coronary occlusion and reperfusion sequence increases the prevalence of reperfusion-induced ventricular fibrillation that is reduced by pericardial biosynthesis of prostaglandins. Pericardial prostaglandin synthesis may serve as a unique antiarrhythmic function by regulating efferent cardiac sympathetic nerve effects.
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PMID:Pericardial prostaglandin biosynthesis prevents the increased incidence of reperfusion-induced ventricular fibrillation produced by efferent sympathetic stimulation in dogs. 211 29

Thirty-one patients with IgG antibodies to cardiolipin (ACLA) were studied to determine their in vivo formation of the platelet aggregating and vasoconstricting substance thromboxane A2 (TxA2) and the platelet inhibiting and vasodilating substance prostacyclin (PGI2). This was done by measurements in urine of their enzymatically formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively, using gas chromatography-mass spectrometry. It is demonstrated that patients with IgG ACLA have a highly significant increase in the biosynthesis of TxA2 compared with age-matched healthy controls (807 +/- 163 [SEM] vs. 230 +/- 15 pg mg-1 creatinine, P = 0.0000005). A significant increment of the formation of PGI2 was also found (189 +/- 23 (SEM) vs. 125 +/- 11 pg mg-1 creatinine, P = 0.03), although this was much less pronounced than that for TxA2. We conclude that the highly increased formation of TxA2, reflecting platelet activation, in patients with IgG ACLA is of pathophysiologic relevance for their tendency to arterial and venous thrombosis and hence that they should be considered for prophylactic treatment with inhibitors of TxA2 formation, like aspirin.
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PMID:Increased thromboxane formation in patients with antiphospholipid syndrome. 212 50

We have previously reported that epithelium-dependent inhibitory factors, both prostanoids and non-prostanoids, can be activated by electrical field stimulation (EFS) and direct nerve stimulation (DNS) in an in vitro nerve-muscle preparation of ferret trachea. In this study we set out to compare the release of the inhibitory prostanoids, PGE2 and PGI2, in preparations with intact and with removed epithelium. Ferret tracheae were mounted in organ baths and phasic contractions were induced by EFS and DNS. The bath concentrations of PGE2 and the PGI2-metabolite 6-keto-PGF1 alpha were measured using radioimmuno assays. The gradual decrease in contractile response to DNS, 2 Hz for 120 min, was 95 +/- 2% of baseline (mean +/- SEM) in preparations with intact epithelium compared with 29 +/- 8% in epithelium-denuded preparations (p less than 0.001). The bath-levels of PGE2 showed a slight but significant (p less than 0.01) increase in denuded preparations with a final bath-concentration at 120 min of 13 +/- 3 pg/ml. The release of PGE2 was more pronounced in preparations with intact epithelium which resulted in a final bath-concentrations of PGE2 of 84 +/- 38 pg/ml which was significantly higher compared with epithelium-denuded preparations and also compared with time-matched controls with the same pattern of contraction induced by DNS alone. The concentrations of 6-keto-PGF1 alpha showed a slight increase which was of comparable magnitude (ns) in intact and denuded preparations. In conclusion this study demonstrates that the cyclooxygenase-dependent component of the epithelium-dependent inhibition of the contractile response to cholinergic nerve stimulation in ferret trachea is mediated by PGE2 but not by PGI2.
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PMID:Epithelium-derived PGE2 inhibits the contractile response to cholinergic stimulation in isolated ferret trachea. 213 19

This study examines prostacyclin production by blood-contacting surfaces within woven vascular prostheses of polydioxanone (PDS), polyglactin 910 (PG910), or Dacron interposed into rabbit infrarenal aortas. Grafts and normal aortic segments were explanted after 1, 3, and 6 months for pulsatile perfusion with Medium-199 for 60 minutes. Aliquots were removed serially for 6-keto-PGF1 alpha assay. After 30 minutes sodium arachidonate (10 micrograms/ml) was added. Specimens were studied by light microscopy, SEM and TEM. Patency in all three groups exceeded 90%. All three showed re-endothelialization at one month. Normal aorta produced low basal 6-keto-PGF1 alpha with a marked evanescent post arachidonate increase. Dacron did not differ from normal aorta. PG910 and PDS both produced significantly less 6-keto-PGF1 alpha post arachidonate at one month but both increased to normal by three months.
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PMID:Prostacyclin production by blood-contacting surfaces of endothelialized vascular prostheses. 214 73

Polymorphonuclear granulocytes (PMN) and eicosanoids such as leukotrienes have been suggested as possible mediators of myocardial ischemia-reperfusion injury. We have investigated the gradients of PMN, 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and leukotriene B4 (LTB4) across the coronary circulation during myocardial reperfusion after cold, cardioplegic arrest in cardiac surgery. Baseline values in arterial blood were 4.4 +/- 0.4 x 10(9)/l, 59 +/- 6 pg/ml and 149 +/- 27 pg/ml (mean +/- SEM) for PMN, 6-keto-PGF1 alpha and LTB4, respectively. They were significantly elevated during cardiopulmonary bypass (CPB). There was a positive correlation between the number of circulating PMN and LTB4 at all sample times during cardiopulmonary bypass (P less than 0.05). At 5 min reperfusion (CPB time: 122 +/- 8 min) PMN, 6-keto-PGF1 alpha and LTB4 were 6.2 +/- 0.5 x 10(9)/l, 696 +/- 117 pg/ml and 280 +/- 60 pg/ml, respectively. The PMN in coronary sinus blood were significantly lower (P less than 0.001) than in arterial blood at 5 min reperfusion, but not at 15 and 30 min. The concentrations of 6-keto-PGF1 alpha and LTB4 were significantly elevated in coronary sinus blood as compared to arterial blood after reperfusion for 5 min (P less than 0.05). Thereafter, no significant gradients were found across the heart, except at 30 min reperfusion when LTB4 was significantly lower in coronary sinus blood. Neither PMN sequestration nor 6-keto-PGF1 alpha and LTB4 production were significantly correlated to aortic cross clamp time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granulocyte and eicosanoid gradients across the coronary circulation during myocardial reperfusion in cardiac surgery. 217 39

To determine whether the clinical, immunological and serological features of patients with silica-associated systemic sclerosis are different from patients with the 'idiopathic' form of systemic sclerosis (SS) we studied 22 underground coal miners who were exposed to silica dust (SD), 30 mine workers who later developed silicosis (S) and 17 mine workers exposed to silica dust who subsequently developed a systemic sclerosis-like disease (SA-SS). The patients with SA-SS had features clinically indistinguishable from individual patients with SS. They all had Raynaud's phenomenon, 14 had cutaneous sclerosis identical to that seen in acrosclerosis and three had a generalized cutaneous sclerosis. Sixteen patients had bibasilar pulmonary fibrosis, 10 had necrosis of the fingertip pulps, nine had oesophageal involvement and only one patient had renal involvement. Antinuclear antibodies and circulating immune complexes were detected in three and eight patients with SD, 14 and five patients with S and in 16 and nine patients with SA-SS, respectively. Anti-Scl-70 antibody was detected in eight of the 17 patients with SA-SS. Evidence for in vivo endothelial cell damage, as determined by elevated levels of von Willebrand factor, was found in nine patients with SD, 14 patients with S and in 10 patients with SA-SS. Following incubation of the patient's serum with confluent cultures of human umbilical vein endothelial cells there was only a significant reduction in calcium ionophore-induced release of prostacyclin with the serum from SA-SS patients compared to that with control serum (NC). The mean +/- SEM release of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin expressed as ng/10(4) cells) decreased from 2.90 +/- 0.27 to 2.01 +/- 0.33 (SD), 3.34 +/- 0.42 to 1.76 +/- 0.31 (S), 1.98 +/- 0.12 to 0.64 +/- 0.07 (SA-SS) and 2.28 +/- 0.33 to 1.36 +/- 0.21 (NC) with 1 and 20% serum, respectively. This study demonstrates that immune complex and antinuclear antibody formation and in vivo endothelial cell damage occurs following occupational exposure to silica. The patients who subsequently develop a systemic sclerosis-like disease have clinical, immunological and serological features which are indistinguishable from the idiopathic form of the disease although as a group the SA-SS patients have a higher prevalence of pulmonary involvement and the anti-Scl-70 antibody.
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PMID:Silica-associated systemic sclerosis is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis. 217 91

Prostaglandins are known to be mediators of inflammation in many tissues. Their fluctuations in gingival crevicular fluid during experimentally induced periodontitis were investigated, together with the possible role of phospholipids, which were measured in normal gingiva and gingiva associated with the chronic periodontitis. Periodontitis was induced in 5 dogs in the lower premolar quadrant; the opposite quadrant was used as a control. A small amount of inter-radicular bone was removed and then a cotton-wrapped stainless steel ligature was placed around each of 3 premolar teeth below the gingival margin to provide an inflammatory irritant. Pocket depth was measured by periodontal probe; crevicular fluid was collected on absorbent paper points. PGs were analysed by HPLC and the results expressed as ng PG/microliter crevicular fluid. Measurements were taken in both quadrants at 1, 3 and 6 weeks after placement of the ligatures; PGI2, 6 keto-F1 alpha, F2 alpha, E2, E1 and D2 were detected in the crevicular fluid. At 1 week, there was no difference in PG levels between experimental and control sides. During week 3, PGI2 and PGE2 increased in the experimental crevicular fluid [214.1 +/- 49.3 (SEM) vs control 87.0 +/- 39.7; p less than 0.05 and 350.0 +/- 115 vs 162.0 +/- 14.7; p less than 0.05, respectively]. At week 6, only PGE2 was elevated in crevicular fluid (207.7 +/- 68.1 vs 99.2 +/- 45; p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gingival crevicular fluid prostaglandins and gingival phospholipids in experimentally-induced periodontitis in the dog. 222 56

The purpose of this study was to test the hypothesis that prostaglandins released from vascular endothelial cells contribute to activation of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in rabbits anesthetized with chloralose. Baroreceptor activity was measured during ramp or step increases in nonpulsatile carotid sinus pressure over a range of 0-175 mm Hg. Exposure of the isolated carotid sinus to inhibitors of prostaglandin formation (indomethacin [n = 10] or aspirin [n = 6]) decreased baroreceptor activity significantly (p less than 0.05). The slope of the pressure-activity relation averaged 0.80 +/- 0.07 %/mm Hg (mean +/- SEM) during control measurements and 0.72 +/- 0.06 and 0.63 +/- 0.05 %/mm Hg during exposure to 10 and 20 microM indomethacin, respectively. Exposure of the carotid sinus to exogenous prostacyclin (PGI2 [n = 11]) increased baroreceptor activity significantly. The slope of the pressure-activity relation averaged 0.89 +/- 0.10, 1.09 +/- 0.09, and 1.26 +/- 0.16 %/mm Hg during control and during exposure to 10 and 20 microM PGI2, respectively. Activity returned to control after removal of PGI2 (0.89 +/- 0.12 %/mm Hg). Removal of endothelium with either a balloon catheter (n = 4) or a jet of a 95% O2-5% CO2 gas mixture (n = 6) decreased the slope of the pressure-activity relation from 0.92 +/- 0.09 to 0.56 +/- 0.08 %/mm Hg (p less than 0.05). Exposure of the denuded sinus to exogenous PGI2 (20 microM [n = 4]) restored activity (slope = 1.09 +/- 0.24 %/mm Hg). Neither indomethacin (n = 5) nor PGI2 (n = 5) nor denudation (n = 5) significantly altered the pressure-diameter relation of the carotid sinus (sonomicrometers), suggesting that the effects on baroreceptor discharge are not caused by altered stretch of the carotid sinus at a given pressure. The results suggest that prostaglandins (e.g., PGI2) released from endothelium contribute in a paracrine manner to activation of baroreceptors during increases in arterial pressure.
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PMID:Prostaglandins contribute to activation of baroreceptors in rabbits. Possible paracrine influence of endothelium. 224 1


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