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F J Zijlstra

Publications and source records attributed to F J Zijlstra.

At least 37 records · Page 2Linked to original sources
PubMed1996

In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells.

OBJECTIVE: Ulcerative colitis (UC) is predominantly a disease of non-smokers and treatment with transdermal nicotine improves symptoms in UC patients, whereas smoking seems to have a deleterious effect in patients with Crohn's disease (CD). In CD the cytokine profile is of a dominant TH1 (T helper 1) pattern whereas in UC the TH2 pattern predominates. To find an explanation for the beneficial effect of nicotine in UC and the deteriorative effect in CD we studied the in-vivo effect of nicotine on the interleukin 2 (IL-2), IL-10 and tumour necrosis factor alpha (TNF alpha) production by human cells. DESIGN: Eleven healthy male non-smokers were included in this study. The volunteers applied nicotine patches with a regulated release of 5 mg (day 1 and 2), 10 mg (day 3 and 4) and 15 mg (day 5, 6 and 7) nicotine per day. METHODS: Heart rate and blood pressure were recorded, nicotine and cotinine concentrations in plasma measured before and after 2, 4 and 7 days of treatment. Non-adherent mononuclear cells (NAC) were isolated from peripheral blood obtained from the subjects before and after 7 days of treatment. The NAC were cultured in the absence or presence of phytohemagglutinin for 48 h. Total amount of IL-2, IL-10 and TNF alpha formed were measured in the supernatants using specific ELISAs. RESULTS: Treatment with nicotine caused a significant inhibition of IL-10 production by NAC. In contrast, nicotine patch treatment had no effect on the production of IL-2 and TNF alpha. CONCLUSIONS: Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function.

Adult↗
PubMed1996

Augmented contraction of the human isolated coronary artery by sumatriptan: a possible role for endogenous thromboxane.

1. The antimigraine drug, sumatriptan, contracts the human coronary artery and, in some patients, elicits chest symptoms (e.g. pressure and pain), particularly after subcutaneous administration. We studied the effects of the thromboxane A2 (TxA2) analogue, U46619 and endothelin-1 on contractile responses to sumatriptan in the human isolated coronary artery as well as the role of endogenously produced TxA2 and endothelin-1 in contractions evoked by sumatriptan. 2. In the presence of U46619 (1 and 3 nM), mean concentration-response curves to sumatriptan in the human coronary artery were shifted vertically due to the initial contraction by U46619, but when this initial contraction was subtracted from the response to sumatriptan, no significant augmentation was observed. However, analysis of the degree of augmentation in individual arterial segments revealed that the augmentation was variable and related inversely to the Emax of sumatriptan in the absence of U46619 (r = 0.78 and 0.81 for 1 and 3 nM, respectively; P < 0.05). 3. Treatment with the TxA2 receptor antagonist, SQ30741 (100 nM), or incubation of vessel segments with aspirin (10 microM), significantly reduced responses to sumatriptan; in aspirin-treated vessel segments, SQ30741 failed to decrease further the contractions to sumatriptan. The decrease in Emax of sumatriptan by both SQ30741 and aspirin correlated significantly with the Emax of sumatriptan without SQ30741 (r = 0.74; P < 0.01) or aspirin (r = 0.94; P < 0.01). In aspirin-treated vessel segments, responses to sumatriptan were significantly augmented in the presence of U46619 (3 nM; P < 0.05). 4. The specificity of SQ30741 was demonstrated by its ability to antagonize coronary artery contractions to U46619 (pA2: 7.54 +/- 0.30), but not endothelin-1. Similarly, incubation with aspirin (10 microM) did not affect contractile responses to endothelin-1, but significantly reduced TxA2 production in coronary artery segments as judged by a decrease in thromboxane B2 (TxB2) from 4.77 +/- 0.98 to 1.38 +/- 0.36 ng g-1 2 h-1. 5. Endothelin-1 (1 nM) did not significantly augment contractions to sumatriptan; there was also no relationship between the degree of augmentation and the control Emax of sumatriptan in the absence of endothelin-1. Furthermore, unlike SQ30741 or aspirin, a high concentration (100 nM) of the non-selective ETA/ETB receptor antagonist, SB 209670, failed to affect contractile responses to sumatriptan. However, SB 209670 potently antagonized coronary artery contractions induced by endothelin-1 with a pA2 of 8.84 +/- 0.32. 6. Compared to control vascular segments, endothelial denudation did not reduce TxA2 production (with endothelium = 2.56 +/- 1.38 vs. without endothelium = 12.32 +/- 4.94 ng TxB2 g-1 2 h-1), suggesting that the production of TxA2 is not confined to the endothelium. The sumatriptan-induced contractions were also unaffected by endothelial denudation. 7. The results of the present study suggest that endogenously produced TxA2 enhances contractions to sumatriptan in the human isolated coronary artery. Such a mechanism may play a role in causing chest symptoms after sumatriptan by potentiating coronary vascular contraction by sumatriptan in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Eicosanoids and lipocortin-1 in BAL fluid in asthma: effects of smoking and inhaled glucocorticoids.

Both smoking and asthma are associated with inflammatory changes in the lung, which may be suppressed with the help of exogenous anti-inflammatory drugs or by the endogenous defense system. Lipocortin-1 (LC-1; annexin-1) is an anti-inflammatory protein present in respiratory tract secretions. We report an inverse correlation between extracellular LC-1 concentration and the bronchoconstrictor prostaglandin (PG) D2 [n = 15, Spearman rank correlation coefficient (rS) = -0.597, P < 0.05] in bronchoalveolar lavage fluid (BALF) from allergic asthmatic patients, together with positive correlations between extracellular LC-1 per milliliter BALF and the prostacyclin (PGI2) metabolite 6-keto-PGF1 alpha (n = 15, rS = 0.480, P < 0.05) and between LC-1 per milliliter BALF and concentration of histamine causing a 20% decrease in forced expired volume in 1 s (n = 15, rS = 0.720, P < 0.01) in these subjects. We found no significant difference between the LC-1 concentration in BALF from nonsmoking asthmatic patients who were receiving inhaled glucocorticoid therapy (2 x 100 micrograms beclomethasone 4 times/day for 2.5 yr; median 186 ng LC-1/mg albumin; n = 6) and those who were not (median 126 ng LC-1/mg albumin; n = 12), perhaps because inhaled drugs deposit predominantly in central airways, which are poorly represented in bronchoalveolar lavage. Both asthmatic and healthy volunteers who smoked had higher levels of LC-1 in their BALF than did their nonsmoking counterparts (e.g., asthmatic smokers, median 317 ng LC-1/mg albumin, n = 10; asthmatic nonsmokers, median 162 ng LC-1/mg albumin, n = 18; P < 0.05), perhaps because smokers' lungs contain more alveolar macrophages, cells that release LC-1. We observed a positive correlation between BALF LC-1 and bronchoalveolar lavage cell number (n = 16, rS = 0.821, P < 0.001). Increased extracellular LC-1 may be part of a protective response of the lung to inflammatory insult. Regulation of prostanoid levels might be one mechanism by which LC-1 suppresses inflammation.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Nicotine inhibits cytokine synthesis by mouse colonic mucosa.

We examined the in vivo effect of nicotine on the synthesis of (pro)inflammatory mediators by mouse colonic mucosa. The synthesis of lipid mediators such as the prostanoids prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2, the 5-lipoxygenase products leukotriene B4 and leukotriene C4 and the platelet activating factor was not affected, whereas the synthesis of the pro-inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha was completely abolished. The beneficial effects of smoking and nicotine in ulcerative colitis could be attributed to this inhibition.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Interleukin-5 and eosinophil cationic protein in nasal lavages of rhinitis patients.

The production of interleukin-5 and eosinophil cationic protein (ECP) in the nasal cavity was examined in 24 patients with rhinitis who were allergic to the house dust mite. During a double-blind placebo-controlled cross-over study, fluticasone propionate aqueous nasal spray (200 micrograms) was administered twice daily for 2 weeks. After four basal nasal lavages provocation with house dust mite extract was performed and nasal lavages were collected every hour for 9.5 h. Interleukin-5 was present in detectable amounts in nasal lavages from patients allergic to house dust mite. Nasal challenge with house dust mite extract caused immediate nasal symptoms and increased levels of interleukin-5. Between 3.5 and 8.5 h after the challenge symptoms recurred and interleukin-5 levels increased, reflecting a late phase reaction. Eosinophil cationic protein, a marker of activated eosinophils, was released between 6.5 and 9.5 h after challenge. Treatment with fluticasone propionate (as an aqueous nasal spray) significantly decreased the evoked interleukin-5 and ECP levels in the late phase reaction. This response was correlated with an improved symptom score. This could indicate that the number and activity of eosinophils are increased during the late phase allergic reaction, a response that is inhibited by corticosteroids.

Adult↗
PubMed1995

Eicosanoid production by rat cerebral endothelial cells: stimulation by lipopolysaccharide, interleukin-1 and interleukin-6.

The capacity of rat cerebral endothelial cells (RCEC) to form eicosanoids was determined after incubation with 14C-labelled arachidonic acid. Prostaglandin E2 (PGE2) was the main metabolite formed by RCEC and was responsible for 54% of the total amount of eicosanoids produced. In contrast, in primary cultures of rat aorta endothelial cells, 32% of the amount of prostaglandins was 6-keto-PGF1 alpha). RCEC treated with 50 ng/ml LPS for 24 h responded with an augmented PGE2 synthesis and 6-keto-PGF1 alpha of 3.4-fold and 2.2-fold, respectively. Cultures treated with IL-1 beta (50 ng/ml) for 3 h showed a stimulation of the release of PGE2 and 6-keto-PGF1 alpha of 2.5- and 4.5-fold, respectively, and 2.0-fold and 2.3-fold, respectively, after IL-6 (50 ng/ml) incubation for 3 h. PGE2 is the main eicosanoid formed by RCEC in response to inflammatory agents, suggesting an important role of the cerebral endothelial cells in the transduction of an inflammatory response in the central nervous system.

Animals↗
PubMed1995

Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis.

The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups. None of these parameters, however, seems to be of practical use as a diagnostic parameter, as there is an overlap between all the levels of these mediators in ascites of liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis group. Soluble intercellular adhesion molecule 1 levels were much higher in plasma than in ascites, in contrast to interleukin-6 levels which were much higher in ascites than in plasma. Soluble intercellular adhesion molecule 1 in ascites correlated with soluble intercellular adhesion molecule 1 in plasma (r = 0.6926, P = 0.0001). Soluble intercellular adhesion molecule 1, interleukin-6 and the number of polymorphonuclear cells in peritoneal fluid correlated during episodes of infection in patients with a peritonitis. For this reason soluble intercellular adhesion molecule 1 and interleukin-6 could be of prognostic value for patients with peritonitis.

Adult↗
PubMed1995

Inflammatory cell number and mediators in bronchoalveolar lavage fluid and peripheral blood in subjects with asthma with increased nocturnal airways narrowing.

BACKGROUND: Increased nocturnal airways narrowing (NAN) in asthma is thought to occur as the result of intensification of inflammatory processes in the airways. In this study we investigated the presence of inflammatory cells and mediators in bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) and assessed their relationship with the occurrence of increased NAN. METHODS: BAL fluid and PB samples were assessed at 16:00 and 04:00 hours, separated by 7 days or more, in eight nonatopic healthy subjects (group 1) and 17 atopic subjects with asthma who were using inhaled bronchodilators only. The latter subjects were prospectively assigned to groups with and without NAN, as defined by a mean circadian peak expiratory flow variation of less than 15% (group 2) and 15% or more (group 3), respectively. RESULTS: Significantly higher eosinophil numbers and inflammatory activation products (eosinophil cationic protein, eosinophil-derived neurotoxin, histamine) were found in BAL fluid and PB from subjects with asthma in comparison with control subjects. However, increased NAN was not generally associated with a circadian fluctuation in cell number and inflammatory mediators in BAL fluid and PB. No differences in inflammatory cell numbers existed that distinguished between groups 2 and 3. However, in group 3 significantly higher BAL prostaglandin D2 levels (70 vs 24 pg/ml; range, 28 to 102 vs 11 to 90 pg/ml; p = 0.04) and serum eosinophil cationic protein levels (17.6 vs 16.1 ng/ml; range, 6.3 to 17.5 vs 6.3 to 60.3 ng/ml; p = 0.03) at 16:00 hours were detected compared with group 2. CONCLUSIONS: Our findings suggest that increased NAN is more likely to occur in subjects with asthma with ongoing increased cellular activation during the day.

Adolescent↗
PubMed1995

High interleukin-6 production within the peritoneal cavity in decompensated cirrhosis and malignancy-related ascites.

To assess the diagnostic and prognostic value of interleukin-6, interleukin 1 beta, and tumor necrosis factor-alpha assays in plasma and ascites, we measured these cytokines in eight patients with malignancy-related ascites and 32 patients with decompensated cirrhosis. Five patients had an episode of bacterial peritonitis, during which one or more ascitic fluid samples were analyzed. Interleukin-6 and tumor necrosis factor-alpha were not significantly different between the cirrhotic and the malignant groups: ascitic interleukin-6 13,816 +/- 15,314 vs 28,138 +/- 23,403 pg/ml, plasma interleukin-6 542 +/- 719 vs 559 +/- 604 pg/ml; ascitic tumor necrosis factor-alpha 19 +/- 50 vs 12 +/- 31 pg/ml, plasma tumor necrosis factor-alpha 3.4 +/- 8.2 vs 6.1 +/- 13.8 pg/ml. During an episode of bacterial peritonitis there was a significant increase only in ascitic interleukin-6 (133,268 +/- 99,743 pg/ml), which declined after antibiotic treatment. None of the parameters was associated with 6-month survival (11 of the 40 patients died within 6 months). There was a correlation (r = 0.675; p = 0.002) between plasma interleukin-6 levels and the Child-Pugh score in patients with cirrhosis, but not with the etiology of the liver disorder. Plasma interleukin-6 levels correlated with IgA levels (r = 0.649; p = 0.004) but not with C reactive protein, sedimentation rate, fibrinogen, IgM or IgG. These results do suggest that interleukin-6 is produced within the peritoneal cavity in hepatic and malignant ascites. There is a sharp increase in the local production of interleukin-6 during an episode of bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Nitric oxide metabolites in nasal lavage fluid of patients with house dust mite allergy.

BACKGROUND: The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined. METHODS: Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house dust mite. In a double blind placebo controlled crossover study fluticasone propionate 200 micrograms aqueous nasal spray was administered twice daily for two weeks. In response to provocation with house dust mite extract (after four basal nasal lavages) nasal lavages were performed every hour for 9.5 hours by washing the nose with saline. In addition, a similar lavage protocol was performed in healthy volunteers with or without challenge with phosphate buffered saline. RESULTS: Nitric oxide is present in nasal lavage fluid in detectable amounts (range 10-50 microM), the level gradually increasing with time in both patients and controls after a decrease during the four basal lavages. Treatment with fluticasone propionate aqueous nasal spray did not affect initial basal production of nitric oxide nor production following provocation with house dust mite extract. CONCLUSIONS: Production of nitric oxide in nasal mucosa determined in sequential nasal washings is not affected by therapeutic doses of intranasal steroids.

Administration, Intranasal↗
PubMed1994

Interactions between cytokines and eicosanoids: a study using human peritoneal macrophages.

To examine the interactions between the main pro-inflammatory cytokines and eicosanoids produced by human inflammatory cells, human peritoneal macrophages (hp-M phi) were isolated from ascitic fluid of patients with portal hypertension. Interactions between interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) were studied by addition or inhibition of several cytokines and eicosanoids: human recombinant IL-1 beta (hrIL-1 beta) addition, LTB4 addition and 5-lipoxygenase inhibition (6-hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiaz ole hydrochloride (E6080)), PGE2 addition and cyclooxygenase inhibition (indomethacin). In hp-M phi hrIL-1 beta stimulated the LTB4 production, while the PGE2 production was inhibited. HrIL-1 beta had no significant effect on IL-6 production in hp-M phi. LTB4 did not regulate IL-1 beta and IL-6 production. Increasing PGE2 down regulated the TNF-alpha production, but did not effect the IL-1 beta and IL-6 production.

Adult↗
PubMed1994

Production of inflammatory mediators by human macrophages obtained from ascites.

Ascites is a readily available source of human macrophages (M phi), which can be used to study M phi functions in vitro. We characterized the mediators of inflammation produced by human peritoneal M phi (hp-M phi) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) was found to be lipopolysaccharide (LPS) concentration dependent (0-10 micrograms/ml) with a maximal production at 10 micrograms/ml and also dependent on the time of exposure to the stimulus (0-36 h). IL-1 beta, IL-6 and TNF-alpha production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 microM. Oxygen radical production was measured in the M phi by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded hp-M phi increases significantly after 15 min. We conclude that LPS stimulation of hp-M phi from liver disease results in similar production of IL-1 beta, IL-6 and TNF-alpha, but that the profile of the eicosanoid production of these M phi stimulated with LPS and A23187 differs from M phi of other origin and species.

Adult↗
PubMed1994

Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes.

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin F1 alpha. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1 alpha: thromboxane B2 and the 6-keto-prostaglandin F1 alpha: LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Effect of nicotine on rectal mucus and mucosal eicosanoids.

Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel.

Animals↗
PubMed1994

Low-dose aspirin inhibits platelet-induced contraction of the human isolated coronary artery. A role for additional 5-hydroxytryptamine receptor antagonism against coronary vasospasm?

BACKGROUND: The beneficial effect of low-dose aspirin in the prevention of coronary vasospasm is well documented. In this study, we investigated the contractile effect of human washed platelets on the human isolated coronary artery. We concentrated on the effect of low-dose aspirin (40 mg/d) taken by the platelet donor and on the efficacy of thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT) receptor antagonists. METHODS AND RESULTS: Human coronary artery segments were suspended in an organ bath set-up for isometric tension measurement. Platelets (10(9) to 3 x 10(10)/L) elicited concentration-dependent contractile responses of the coronary artery segments, reaching 28.4 +/- 7.1% of contractions induced by 100 mmol/L K+. The contractile response tended to be decreased in vessel segments with histological signs of early atherosclerosis. Contraction was significantly attenuated after pretreatment of the vessel segments with ketanserin (5-HT2 receptor antagonist, 1 mumol/L) or SQ30741 (TXA2 receptor antagonist, 0.01 mumol/L), reaching 8.8 +/- 2.3% and 3.2 +/- 2.2% of contraction to 100 mmol/L K+, respectively. Platelets obtained from the same platelet donors after they had taken aspirin (40 mg/d for 7 to 13 days) caused significantly lower contractile responses (7.6 +/- 2.7% of 100 mmol/L K+) associated with an almost selective inhibition of the synthesis of thromboxane measured in the organ bath solution (untreated platelets, 2.19 +/- 0.43 nmol/L; aspirin-treated platelets, 0.66 +/- 0.05 nmol/L). The amount of 5-HT secreted in the organ bath remained unaltered (65.17 +/- 9.94 and 64.03 +/- 8.98 nmol/L, respectively). This explains why ketanserin significantly attenuated the residual contractile responses caused by platelets obtained from aspirin-treated subjects, whereas SQ30741 caused minor, nonsignificant additional attenuation. CONCLUSIONS: The results of the present study therefore suggest that additional antagonism of the contractile 5-HT receptors in the coronary artery may increase the efficacy of low-dose aspirin in vivo.

Adolescent↗
PubMed1993

Increased platelet activating factor synthesis in experimental colitis after diclofenac and 5-amino-salicylic acid.

We examined the role of platelet activating factor in dextran induced colitis in mice. The release of pro-inflammatory platelet activating factor by colonic mucosa after the application of prednisolone was markedly decreased, unaffected after treatment with the platelet activating factor receptor antagonist BN52021 and significantly increased after treatment with 5-amino-salicylic acid and diclofenac. This increase of platelet activating factor could be responsible for the harmful effects often seen after treatment with specific cyclooxygenase inhibitors during inflammation.

Aminosalicylic Acid↗
PubMed1993

Inflammatory mediators and activity of human peritoneal macrophages.

Human peritoneal macrophages (hp-M phi) are a source of inflammatory mediators. After stimulation in vitro for 24 h with LPS there was a significant increase in cytokine production (IL-1, IL-6 and TNF alpha), but not in the production of eicosanoids from endogenous arachidonate. Leukotrienes are the predominant eicosanoids formed after stimulation with calcium ionophore for 15 min, while prostaglandin formation is insignificant. The fluorescence intensity of TPA-stimulated and DHR123 loaded hp-M phi (a measure of the respiratory burst) increases significantly in a short period of time. Hp-M phi will be useful as a model for testing the effects of anti-inflammatory drugs on eicosanoid and cytokine production and respiratory burst activity in vitro.

Ascitic Fluid↗