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

To determine the role of the prostaglandins on renal norepinephrine release, the effect of inhibition of prostaglandin synthesis was examined in anesthetized dogs during reflex activation of the renal adrenergic nerves. Hypotension increased the renal vein plasma concentrations of norepinephrine from 380 +/- 59 to 608 +/- 106 pg/ml (mean +/- SEM; P less than 0.01) and of PGE2 from 55 +/- 7 to 81 +/- 41 pg/ml (P less than 0.05). Subsequent administration of indomethacin or meclofenamate lowered the renal venous concentration of PGE2 to 26 +/- 3 pg/ml (P less than 0.01), had no significant effect on the norepinephrine concentration (620 +/- 89 pg/ml). Administration of indomethacin or meclofenamate to dogs with sodium depletion lowered renal venin plasma concentration of PGE2 from 108 +/- 40 to 20 +/- 3 pg/ml (0.05 less than P less than 0.1) but had no effect on the renal venous norepinephrine concentration (475 +/- 50 vs. 397 +/- 46 pg/ml). In dogs fed a normal salt diet, inflation of a balloon placed in the thoracic inferior vena cava lowered cardiac output and increased the renal venous concentrations of norepinephrine from 212 +/- 60 to 496 +/- 112 pg/ml (P less than 0.01) and of PGE2 from 28 +/- 5 to 96 +/- 18 pg/ml (P less than 0.01). Subsequent administration of indomethacin lowered the renal venous concentration of PGE2 to 16 +/- 5 pg/ml (P less than 0.01), but had no significant effect on the concentration of norepinephrine (548 +/- 91 pg/ml). During the three experimental conditions examined, renal blood flow was lowered by inhibition of prostaglandin synthesis. These results in the dog suggest that the attenuating effect that prostaglandins exert on the renal vascular action of the adrenergic nerves is not due to inhibition of norepinephrine release.
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PMID:Role of the prostaglandin in norepinephrine release during augmented renal sympathetic nerve activity in the dog. 701 19

A method for the detection of prostaglandin E (PGE) in crevicular fluid has been developed which provides a sensitive, noninvasive technique for measurement of local concentrations of this mediator of inflammation. Assay sensitivity sufficient for the detection of 4 picograms of PGE2 was achieved by utilizing a high-affinity anti-PGE2 antibody, a solid-state second antibody and low isotope concentrations. The method permits detection of concentrations equivalent to 10(-8) M PGE2 in 1 microliter of crevicular fluid. Crevicular fluid PGE (CFPGE) concentrations were determined in samples from 12 patients with periodontal disease. Patients with periodontitis had significantly higher mean CFPGE concentrations than patients with gingivitis (179.5 +/- 51.4 pg/microliter vs 32.1 +/- 15.5 pg/microliter, mean +/- SEM). Periodontitis sites were selected on the basis of clinical and radiographic evidence of periodontal destruction. Some sites displayed low CFPGE levels, while others had CFPGE concentrations which were elevated tenfold, suggesting the presence of both inactive and active periodontal lesions. CFPGE levels greater than 100 pg/microliter were positively associated with gingival erythema and pain on probing.
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PMID:Measurement of prostaglandin E in crevicular fluid. 703 2

The fetus and prematurely delivered newborn lamb have high concentrations of circulating PGE2 that may play a hormonal role, particularly in maintaining the patency of the ductus arteriosus. We studied the ability of the isolated, perfused lung from immature (100 +/- 2 days gestation, +/- SEM n = 8) and near term (142 +/- 1 days, n = 10; term is 150 days) lamb fetuses to metabolize PGE2 as a function of PGE2 concentration in the perfusate. After an intra-arterial infusion of 3H-PGE2 and 14C-inulin (to act as a marker of extracellular space), the bulk of the 14C-inulin was rapidly cleared through the isolated lung and the majority of the 3H activity appeared after the 14C activity had fallen to negligible values. The 3H activity that was retained longer in the lung was primarily associated with the 15-keto prostaglandin E2 and 15-keto-13,14 dihydro prostaglandin E2 metabolites. Lungs from immature fetal lambs metabolized 25% less PGE2 than did lungs from animals near term. This is consistent with our prior observation that premature lambs have decreased plasma clearance rates (in vivo) and elevated circulating concentrations of PGE2 when compared with term newborn lambs.
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PMID:Effect of gestational age on pulmonary metabolism of prostaglandin E1 & E2. 723 70

The contribution of hepatocytes to liver prostaglandin (PG) synthesis Is not clear. We compared prostaglandin synthesis in homogenates of whole liver, freshly isolated hepatocytes, and mixed non-parenchymal cells from the same rat livers, and optimized the assay. Whole liver homogenates made 27.2 +/- 7.1 mg PGE2/mg protein/5 min (+/- SEM, n = 4 livers). Hepatocyte homogenates made 39 +/- 9% as much PGE2/mg protein as did the matched whole livers. Non-parenchymal cell homogenates made slightly more PGE2 than whole liver, but much more PGD2. Subsequent studies showed that fresh hepatocyte suspensions contain significant contamination with non-parenchymal cells. Homogenates from ricin-purified hepatocyte monolayers made at least half as much PGE2 as did conventional monolayers. However, taking cellular purity into account, hepatocytes must contain much less than a third of liver cyclooxygenase activity.
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PMID:The contribution of hepatocytes to prostaglandin synthesis in rat liver. 748 72

The sunburn response is markedly reduced by dietary fish oil rich in omega-3 polyunsaturated fatty acids. Because prostaglandins mediate the vasodilatation, we examined the effect of fish oil on ultraviolet (UV) B-induced prostaglandin metabolism. In addition we assessed the potential photoprotective effect of fish oil in light-sensitive patients. Thirteen patients with polymorphic light eruption received dietary supplements of fish oil rich in omega-3 polyunsaturated fatty acids for 3 months. At baseline and 3 months, the minimal erythema dose of UVB irradiation was determined, and a graded UVA challenge given to a forearm to assess the threshold dose for papule provocation. Suction blisters were raised on the other forearm, on control skin, and on skin irradiated with four times the minimal erythema dose of UVB 24 h previously, and blister fluid prostaglandin E2 was measured by radioimmunoassay. Following 3 months of fish oil, the mean minimal erythema dose of UVB irradiation increased from 19.8 +/- 2.6 to 33.8 +/- 3.7 mJ/cm2 (mean +/- SEM), p < 0.01. The UVA provocation test was positive in 10 patients at baseline, and after 3 months nine of these showed reduced sensitivity to papule provocation, p < 0.001. Before fish oil, PGE2 increased from 8.6 (SEM 2.1) ng/ml in control skin to 27.2 (11) ng/ml after UVB, p < 0.01. Following 3 months of fish oil, PGE2 decreased to 4.1 (1) and 9.6 (2.4) ng/ml in control and irradiated skin, respectively, p < 0.05. Reduction of UV-induced inflammation by fish oil may be due, at least partially, to lowered prostaglandin E2 levels. The photoprotection against UVA-provocation of a papular response suggests a clinical application for fish oil in polymorphic light eruption.
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PMID:Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption. 756 Nov 54

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.
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PMID:Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha. 806 18

Inhaled furosemide protects asthmatic subjects against bronchial obstruction caused by indirect provocants. We have attempted to correlate the protective effect of furosemide with its ability to alter prostaglandin (PG) synthesis by the airway epithelium. Human epithelial cells from nasal polyps and bronchi were cultured in DME-Ham's F12 medium with 10% fetal calf serum. Confluent cells (days 6 through 8) were incubated for 30 min in fresh medium, and the PGs in the supernatant were measured by radioimmunoassay. Spontaneous output (ng.ml-1.mg-1 cell protein) was as follows (mean +/- SEM): PGE2 = 7.74 +/- 2.10 (n = 12), PGF2 alpha = 1.66 +/- 0.12 (n = 15), 6-keto-PGF1 alpha = 4.32 +/- 1.37 (n = 11), PGD2 = 0.73 +/- 0.16 (n = 11) for bronchial cells and PGE2 = 7.24 +/- 0.80 (n = 32), PGF2 alpha = 1.38 +/- 0.12 (n = 17), 6-keto-PGF1 alpha = 6.79 +/- 2.50 (n = 15), PGD2 = 0.42 +/- 0.07 (n = 17) for nasal cells. Incubation with arachidonic acid (25 micrograms/ml) for 30 min significantly increased the amounts of the four PGs. Incubation with furosemide (10(-4) M) for 30 min caused a marked reduction in both basal and arachidonic acid-stimulated production of PGE2 and PGF2 alpha but did not reduce production of 6-keto-PGF1 alpha and PGD2. Incubation with bumetanide (10(-4) M) for 30 min did not modify the PGE2 synthesis by nasal epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of furosemide on prostaglandin synthesis by human nasal and bronchial epithelial cells in culture. 813 54

Previous studies have suggested that the endogenous release of inhibitory prostanoids limits the bronchoconstrictor response to repeated exercise. The aim of our study was to determine whether inhaled prostaglandin (PG)E2 attenuates exercise-induced bronchoconstriction or methacholine airway responsiveness in asthmatic subjects. Eight subjects with mild stable asthma and exercise bronchoconstriction were studied on 4 separate days, 48 h apart. Subjects inhaled PGE2 or placebo in a randomized, crossover, double-blind fashion, 30 min prior to an exercise challenge or a methacholine challenge. PGE2 inhalation significantly attenuated exercise bronchoconstriction. The mean maximal %fall in FEV1 after exercise was 26% (SEM 3.7%) after placebo, and was 9.7% (SEM 2.7%) after PGE2 (p < 0.001). PGE2 also significantly reduced the duration of exercise bronchoconstriction (p = 0.034). However, PGE2 did not significantly attenuate methacholine airway responsiveness. The geometric mean methacholine provocative concentration causing a 20% fall in FEV1 (PC20) was 0.77 (%SEM 1.48) after placebo day, and 1.41 (%SEM 2.20) after PGE2 (p = 0.30). These results demonstrate that inhaled PGE2 markedly attenuates exercise bronchoconstriction in asthmatic subjects and suggest that this effect is not occurring through functional antagonism of airway smooth muscle.
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PMID:Effect of inhaled PGE2 on exercise-induced bronchoconstriction in asthmatic subjects. 817 53

This study was performed to examine the immunosuppressive effect of a 5-lipoxygenase inhibitor, AA-861, on liver transplantation in rodents, and also to examine the production of eicosanoids during rejection of liver allograft in these animals. Rats were divided into three groups: group I (syngenic orthotopic liver transplantation from LEW to LEW), group II (allogenic OLT from ACI to LEW with dimethyl sulfoxide), and group III (allogenic OLT from ACI to LEW with AA-861 [20 mg/kg/day] s.c. dissolved in DMSO). Histological examinations were performed, survival time was monitored, and eicosanoid levels at 3, 5, and 7 days after transplantation were measured. Mean survival time in group III was significantly longer than that in group II (36.0 +/- 6.8 vs. 11.1 +/- 0.7 days, mean +/- SEM; P < 0.01). Histologically, the degree of rejection in group III was moderate compared with that in group II. On day 3, the LTB4 level in group II was significantly higher than that in group I (3361 +/- 985 vs. 407 +/- 70 pg/ml, P < 0.05), and the PGE2 level in group III was significantly higher than that in group 1 (50.3 +/- 4.8 vs. 23.5 +/- 4.7 pg/ml, P < 0.01) and in group II (32.9 +/- 4.2 pg/ml, P < 0.05). These findings suggest that AA-861 reduced liver allograft rejection by suppressing the elevation of 5-lipoxygenase products and increasing PGE2 production in the early stage of rejection.
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PMID:The immunosuppressive effect of 5-lipoxygenase inhibitor on liver allotransplantation in rats. 821 43

Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p < 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p < 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p < 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.
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PMID:Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin. 834 98


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