Biomedical subjects

A Riutta

Publications and source records attributed to A Riutta.

At least 37 records · Page 2Linked to original sources

PubMed1996

Prostacyclin and thromboxane A2 synthesis are increased in acute lower limb ischaemia.

Prostacyclin (PGI2) and thromboxane A2 (TXA2) play an important role in the pathophysiology of various cardiovascular diseases. The balance between PGI2 and TXA2 regulates the interaction between platelets and the vessel wall in vivo. In this study we measured PGI2 and TXA2 synthesis by analysing their urinary index metabolites 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2, respectively, in acute (10 patients) and chronic (10 patients) lower limb ischaemia. Both PGI2 and TXA2 synthesis were increased about two-fold in patients with acute lower limb ischaemia compared to chronic lower limb ischaemia. However, the PGI2/TXA2 ratio was more or less the same in acute and chronic lower limb ischaemia. In patients with acute lower limb ischaemia caused by thrombotic occlusion, PGI2 and TXA2 formation were about two times higher than in patients with acute lower limb ischaemia caused by embolic occlusion. Elevation of PGI2 and TXA2 synthesis in acute lower limb ischaemia may reflect increased platelet-vascular wall interactions without changing the PGI2/TXA2 ratio.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Effects of noradrenaline and dopamine infusions on arachidonic acid metabolism in man.

We infused noradrenaline (0.025 micrograms/kg/min for 60 min, n=7) and dopamine (3.0 micrograms/kg/min for 60 min, n=6) into healthy male volunteers to study the effects of these catecholamines on in vivo thromboxane A2, prostacyclin and leukotriene E4 production measured as urinary excretions of 11-dehydro-thromboxane (TX) B2, 2,3-dinor-6-keto-prostaglandin (PG) F1alpha and leukotriene (LT) E4, respectively. Plasma noradrenaline and dopamine concentrations were 2.9+/-0.3 and 233+/-17 nmol/l at the endo fo the noradrenaline and dopamine infusions, respectively. Noradrenaline decreased thromboxane production and increased leukotriene production almost two fold. It had hardly any effect on prostacyclin production. Dopamine had no significant effects on any of the variables, however, it had a tendency to increase prostacyclin and leukotriene production. The results indicate that noradrenaline is a more important modulator of arachidonic acid metabolism than dopamine in vivo.

Adrenergic alpha-Agonists↗

PubMed1995

Effects of NO-donors, SIN-1 and GEA 3175 on prostacyclin and cGMP synthesis in cultured rat endothelial cells.

The aim of the present study was to investigate, whether nitric oxide (NO) modifies prostacyclin synthesis in endothelial cells. Two different NO-donors: SIN-1 (3-morpholino sydnonimine) and GEA 3175 (4-aryl-substituted oxatriazol derivative), and the NO-synthesis inhibitor; L-NAME were used. Endothelial cells were incubated with the tested compounds with or without Ca ionophore A23187 stimulation. SIN-1 (> 33 microM) and GEA 3175 (> 1 microM) increased the endothelial cGMP levels independently of A23187 stimulation. SIN-1 did not influence prostacyclin synthesis. GEA 3175 (> 33 microM) increased prostacyclin synthesis up to 2-fold, when incubated without A23187. GEA 3175 with A23187 induced about 30% inhibition in prostacyclin synthesis. L-NAME decreased unstimulated prostacyclin synthesis and this inhibition was reversed by GEA 3175. Obviously NO is able to modulate prostacyclin synthesis, however, much higher concentrations are needed than those to increase cGMP synthesis.

Animals↗

PubMed1995

Smoking cessation and nicotine substitution modulate eicosanoid synthesis ex vivo in man.

The effects of smoking cessation with and without nicotine substitution on prostaglandin E2, leukotriene B4, leukotriene E4, and thromboxane B2 synthesis ex vivo in man were investigated. Blood samples were obtained from 20 healthy non-smoking controls and from 30 healthy smoking volunteers before and 3, 7 and 14 days after smoking cessation. Half of the smokers used nicotine chewing gum as a substitution therapy. Urinary cotinine and trans-3'-hydroxycotinine as well as thiocyanate excretions were used as indicators for the use of nicotine chewing gum and smoking, respectively. Prostaglandin E2, leukotriene E4, and thromboxane B2 were measured from whole blood after calcium ionophore A23187 stimulation by direct radioimmunoassay and leukotriene B4 by RP-HPLC. Prostaglandin E2 and thromboxane B2 syntheses were about three times and leukotriene B4 and E4 syntheses four times higher in smokers than in controls. Three days after smoking cessation without nicotine substitution, levels were lowered significantly to about 70%, 80%, 45% and 60% of the initial values; and after 14 days to 55%, 80%, 45% and 50%, respectively. In the nicotine substitution group no significant decreases were seen during the two-week follow-up. The increased level of eicosanoid synthesis detected in smokers in this ex vivo study may contribute to the harmful cardiovascular effects of smoking. Long-term nicotine substitution might diminish the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo.

Adult↗

PubMed1995

Phenols inhibit prostaglandin E2 synthesis in A23187-stimulated human whole blood and modify the ratio of arachidonic acid metabolites.

We have previously demonstrated that the phenolic compounds catechol, hydroquinone, and phenol increase the prostaglandin (PG) E2/leukotriene (LT) B4 ratio in human polymorphonuclear leukocytes (PMNs), while resorcinol has the opposite effect. However, in human whole blood phenols have a different effect on the thromboxane (TX) B2/LT ratio than in PMNs on the PGE2/LTB4 ratio. To establish whether the discrepancy between the results of our previous studies is due to different indicators of prostaglandin H synthase activity in PMNs (PGE2) and in whole blood (TXB2), we measured the effect of phenols on PGE2 synthesis in whole blood. The phenols only inhibited PGE2 synthesis (IC50 values for resorcinol, catechol, hydroquinone, and phenol of 10 microM, 10 microM, 60 microM and 700 microM, respectively). No significant stimulatory activity was seen as earlier in PMNs. Thus, the effect of phenols on PGE2 synthesis in whole blood is different from that in PMNs, although their order of potency to inhibit PGE2 synthesis is the same.

Arachidonic Acid↗

PubMed1995

Noradrenaline and dopamine infusions modulate arachidonic acid cyclooxygenase and 5-lipoxygenase pathways ex vivo in man.

We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (TX/LT) ratio in whole blood in healthy volunteers. The aim of the present study was to see whether other catecholamines--noradrenaline and dopamine--are also capable of modulating arachidonic acid (AA) metabolism in man. Low doses of noradrenaline (0.025 microgram/kg/min) and dopamine (3.0 micrograms/kg/min), which did not change hemodynamics, were infused for 60 min into healthy male volunteers. Both dopamine and noradrenaline decreased TX synthesis stimulated by spontaneous clotting, but no remarkable effect was seen when calcium ionophore A23187 was used as a stimulus. Dopamine but not noradrenaline increased prostaglandin E2 (PGE2) synthesis in A23187-stimulated whole blood. They both marginally decreased LTB4 formation in A23187-stimulated whole blood. The findings indicate that not only adrenaline but also noradrenaline and dopamine modulate AA metabolism in man.

Adult↗

PubMed1995

Effects of propofol and Intralipid on immune response and prostaglandin E2 production.

The present study evaluated the effects of propofol and its solvent Intralipid on the immune response and in vivo prostaglandin E2 production in patients during induction of anaesthesia and in healthy volunteers after Intralipid injection. Fifteen female patients (median age 48 years, ASA 1-2) scheduled for uterine dilatation and curettage were randomly assigned to two groups. In group 1 propofol (median dose 3.1 mg.kg-1) and in group 2 thiopentone (median dose 6.0 mg.kg-1) were injected intravenously over 60 s. Surgery was started after collection of the last blood sample. In the second part of this study, Intralipid 10% 0.3 ml.kg-1 was injected intravenously in eight healthy volunteers (four women and four men, median age 32 years) over 60 s. Plasma bicyclo-PGE2 concentrations increased during anaesthesia induction in both anaesthetic groups (p < 0.01). By contrast, no changes were seen in plasma bicyclo-PGE2 concentrations after Intralipid injection in volunteers. Lymphocyte proliferative responses to mitogens did not change during anaesthesia induction in patients. In volunteers, Intralipid injection caused a slight increase in T-cell percentages (p < 0.01) and unstimulated lymphocyte proliferative responses (p < 0.05), but it did not affect other lymphocyte subsets and immunoglobulin production. Intralipid and propofol were not found to be immunosuppressive at clinical doses used during anaesthesia induction.

Adult↗

PubMed1994

Effects of Trolox C and SIN-1 on arachidonic acid metabolism and on cyclic GMP formation in leukocytes.

The effects of Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a vitamin E analogue, (60-900 microM) and SIN-1 (3-morpholino sydnonimine), a nitric oxide donor, (30-3000 microM) on arachidonic acid metabolism and on cyclic GMP formation in calcium ionophore A23187 (calcimycin)-stimulated human polymorphonuclear leukocytes were investigated. Trolox C elicited a dose dependent decrease in leukotriene B4 levels and increase in prostaglandin E2 levels but did not affect cyclic GMP levels. SIN-1 dose dependently inhibited leukotriene B4 and stimulated prostaglandin E2 and cyclic GMP formation. Dibutyryl cyclic GMP did not affect the formation of leukotriene B4 and prostaglandin E2. Trolox C (180 microM), which itself had no effect on cyclic GMP levels, enhanced the effect of SIN-1 (100 microM) on cyclic GMP levels more than 5-fold. The effects of SIN-1 on arachidonic acid metabolism seem to be independent of cyclic GMP and are probably due to nitric oxide. In this experimental model both Trolox C and SIN-1 have similar actions on the prostaglandin/leukotriene ratio, and Trolox C potentiates the SIN-1-induced increase in cyclic GMP levels.

Antioxidants↗

PubMed1994

Selective solid-phase extraction of urinary 2,3-dinor-6-ketoprostaglandin F1 alpha for determination with radioimmunoassay.

This paper describes a method for selective two-step solid-phase extraction of urinary 2,3-dinor-6-ketoprostaglandin F1 alpha for reliable determination with radioimmunoassay. In the immunoreactivity profile of non-selectively extracted urine after HPLC separation, over 90% of the total 2,3-dinor-6-ketoprostaglandin F1 alpha immunoreactivity consisted of interfering material coeluting with 6-ketoprostaglandin F1 alpha and 2,3-dinor-6-ketoprostaglandin F1 alpha. Among the alkyl silica sorbents studied (methyl, butyl, octyl, and octadecyl), an efficient separation of 2,3-dinor-6-ketoprostaglandin F1 alpha from 6-ketoprostaglandin F1 alpha and the lowest immunoreactive concentration of analyte were achieved in extraction on the methyl silica sorbent by elution of 2,3-dinor-6-ketoprostaglandin F1 alpha with chloroform: hexane (85:15, v/v) from the cartridge. The proportion of specific immunoreactivity could be further increased by two-step extraction of sample on methyl silica cartridges, first at pH 3 and then at pH 10 using diethyl ether:hexane (85:15, v/v) and chloroform as eluent, respectively. After this, a high correlation was found with concentrations of samples determined by radioimmunoassay using three different antisera. A significant correlation of values was also observed between samples measured by radioimmunoassay and those measured by GC-MS. The values of 12-h excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha in eight volunteers (268 +/- 204 ng/g creatinine, mean +/- SD) as well as the inhibitory effect of acetylsalicylic acid (74 +/- 12%) are in accordance with those reported in the literature. This selective extraction procedure provides a high validity in radioimmunoassay without requiring subsequent TLC or HPLC purification.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Adrenaline infusion increases systemic prostacyclin production in man.

We have previously shown that adrenaline infusion induces an almost twofold increase in systemic thromboxane synthesis, measured as urinary 11-dehydrothromboxane B2. The purpose of the present study was to investigate whether high levels of adrenaline, found e.g. in heavy physical exercise and myocardial infarction are involved in the regulation of prostacyclin synthesis. To this end the effect of adrenaline infusion (0.1 microgram/kg/min for 45 min and thereafter 0.2 microgram/kg/min for 15 min) on prostacyclin synthesis in healthy male volunteers was investigated. Adrenaline infusion produced an over twofold increase in systemic prostacyclin synthesis, measured as urinary 2,3-dinor-6-keto-prostaglandin F1 alpha. Our study demonstrates that high circulating levels of adrenaline are associated with increased formation of prostacyclin.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Nicotine and cotinine modulate eicosanoid production in human leukocytes and platelet rich plasma.

We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leukotriene B4 production in human polymorphonuclear leukocytes and on thromboxane B2 formation in human platelet-rich plasma, stimulated by calcium ionophore A23187. Nicotine and cotinine dose-dependently increased prostaglandin E2 synthesis in polymorphonuclear leukocytes from 25% (0.5 nM) up to nearly four-fold (0.5 mM). In concentrations found in the plasma of smokers, nicotine and cotinine increased prostaglandin E2 production by 33% (50 nM) and 50% (500 nM), respectively. Nicotine and cotinine equipotentially reduced both leukotriene B4 production in polymorphonuclear leukocytes and thromboxane B2 production in platelet rich plasma, the inhibition increasing from 20% (0.5 nM) to 60% (0.5 mM). The stimulation of prostaglandin E2 and inhibition of leukotriene B4 and thromboxane B2 production by nicotine and cotinine may due to the pyridine moiety that these compounds have in common.

Blood Platelets↗

PubMed1993

Modulation of arachidonic acid metabolism by phenols: relation to positions of hydroxyl groups and peroxyl radical scavenging properties.

We have shown earlier that catecholamines have opposite regulative effects on prostaglandin (PG)E2 and leukotriene (LT)B4 formation with a receptor-independent mechanism in human polymorphonuclear leukocytes (PMNs) and whole blood. To shed further light on the mechanisms involved and structure-action relationship, we tested the effects of phenols (catechol, hydroquinone, phenol, and resorcinol) on the synthesis of PGE2 and LTB4 in human A23187-stimulated PMNs. To study the mechanism of how phenols influence PGE2 and LTB4 synthesis, their peroxyl radical-scavenging properties were analyzed. In general, low concentrations of phenols stimulated (catechol > hydroquinone >> phenol) and high concentrations inhibited (resorcinol > catechol > hydroquinone > phenol) PGE2 formation. Resorcinol was different from the other phenols: It did not stimulate PGE2 synthesis at all, but it was effective inhibitor at high concentrations. Phenols had only an inhibitory effect on LTB4 formation (catechol = hydroquinone >> phenol > resorcinol). The order of both stochiometric factors and reactivities of phenols for scavenging peroxyl radicals was catechol > hydroquinone > resorcinol >> phenol. According to these results, phenols having hydroxyl groups in ortho- or paraposition have the greatest stimulative effect on PGE2 synthesis, the highest inhibitory action on LTB4 synthesis, and are good antioxidants. Resorcinol, having hydroxyl groups in the metaposition, behaves differently. It neither stimulates PGE2 nor inhibits LTB4 formation, but it is the most potent inhibitor of PGE2 formation. In spite of resorcinol's two hydroxyl groups, it mimics as an antioxidant phenol more than catechol and hydroquinone.

Antioxidants↗

PubMed1992

Solid-phase extraction of urinary 11-dehydrothromboxane B2 for reliable determination with radioimmunoassay.

In this paper we elaborate a one-step procedure for the selective extraction of urinary 11-dehydrothromboxane B2 on octylsilyl silica cartridges for reliable determination with radioimmunoassay. The immunoreactivity profile of nonselectively extracted urine after HPLC separation showed that as much as 70% of the total 11-dehydrothromboxane B2 immunoreactivity comigrates with polar interfering material. Its amount could be considerably decreased using acetonitrile:water (18:82, v/v) as wash solvent before elution of 11-dehydrothromboxane B2 from the cartridge. Alternatively, very high immunoreactive purity was achieved without the preceding wash step by selective elution of the analyte with dichloromethane:hexane (70:30). After both optimized steps in the extraction procedure were combined, immunoreactivity was found only in HPLC fractions corresponding to the retention volume of authentic 11-dehydrothromboxane B2. The homogeneity of this immunoreactivity was confirmed by two-step HPLC separation. A significant correlation of values was observed between samples measured after extraction and those measured after subsequent HPLC purification. A high correlation was also found with concentrations determined by radioimmunoassay using four different antisera. The values of 24 h excretion of 11-dehydrothromboxane B2 in 10 male volunteers (595 +/- 114 ng/g creatinine, mean +/- SD) as well as the inhibitory effect of acetylsalicylic acid (80 +/- 13%) closely correspond with those reported in the literature. This selective extraction procedure provides a high validity in radioimmunoassay without requiring any further purification step.

Chromatography, High Pressure Liquid↗

PubMed1992

Effects of catecholamines on eicosanoid synthesis with special reference to prostanoid/leukotriene ratio.

Catecholamines (adrenaline, dopamine, and noradrenaline) stimulate prostanoid synthesis by acting as "cosubstrates." On the other hand, many inhibitors of leukotriene synthesis, such as nordihydroguaiaretic acid and caffeic acid, have a catecholic structure. Catecholamines have opposite effects on prostanoid and leukotriene synthesis in human polymorphonuclear leukocytes and whole blood. Basic phenols (catechol, hydroquinone, and phenol) also increase the prostanoid/leukotriene ratio in polymorphonuclear leukocytes. These actions correlate to their antioxidant capacities and oxidation potentials, and they are not mediated via adrenergic receptors. There is only limited knowledge about the effects of natural catecholamines on the prostanoid/leukotriene ratio in vitro and in vivo. Indirect data suggest that catecholamines could increase prostanoid production in physiological or pathological situations, such as heavy physical exercise, myocardial infarction, and surgical stress. This interaction may also be of clinical importance in asthma, gastric ulcer, and psoriasis, where decreased prostanoid/leukotriene ratios have been reported.

Animals↗

PubMed1992

Adrenaline stimulates thromboxane and inhibits leukotriene synthesis in man.

Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism in human polymorphonuclear leukocytes and whole blood in vitro. The hypothesis that high levels of adrenaline, found e.g. in myocardial infarction, are involved in the regulation of arachidonic acid metabolism was tested. Adrenaline (0.1 micrograms/kg per min for 45 min and thereafter 0.2 micrograms/kg per min for 15 min) was infused to healthy male volunteers to mimic relationships between high levels of adrenaline and arachidonic acid metabolism in myocardial infarction. Adrenaline infusion increased Ca ionophore A23187-induced TXB2 formation in whole blood. The effect was smaller when spontaneous clotting was used as a stimulus. Urinary 11-dehydro-TXB2 excretion, an indicator of total in vivo thromboxane synthesis, increased twofold. Adrenaline infusion decreased both LTB4 and LTE4 synthesis in A23187-stimulated whole blood. These results demonstrate that high levels of adrenaline influence the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism differentially in man.

Adult↗

PubMed1991

Catecholamines decrease leukotriene B4 and increase thromboxane B2 synthesis in A23187-stimulated human whole blood.

Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic compound without adrenergic receptor activity) decreased leukotriene (LT)B4 synthesis in A23187-stimulated human whole blood. Salbutamol, a non-catecholic beta 2-adrenergic agonist, did not influence LTB4 synthesis. Catecholamines stimulated thromboxane (TX)B2 synthesis with a concomitant inhibition of LTB4 synthesis; caffeic acid and salbutamol did not stimulate TXB2 synthesis. These results, obtained in A23187-stimulated whole blood, which also takes into account the complex interaction between different cell types, are similar to our previous results with polymorphonuclear leukocytes. Catecholamines show an opposite effect on lipoxygenase and cyclooxygenase pathways, which may give rise to a marked change in LT/TX ratio in physiological or pathological conditions where sufficient concentrations of catecholamines are present.

Calcimycin↗

PubMed1991

Factors affecting the reliability of direct radioimmunoassay for urinary 11-dehydrothromboxane B2 with 125I-labelled ligand: albumin and heterogeneous immunoreactivity.

The determination of 11-dehydrothromboxane B2 (11-dehydro-TXB2) from unextracted human urine was studied by means of a specific radioimmunoassay based on the use of the 125I-labelled tyrosine methyl ester derivative of 11-dehydro-TXB2 as radioligand. The assay was evaluated in various incubation media by either dextran-coated charcoal (DCC) or polyethylene glycol (PEG) separation. Both the non-specific and the specific binding showed high variation in different assay media with DCC separation but with the use of PEG separation, however, the non-specific binding was constant. The verification tests carried out in both separation systems revealed a high variation of equilibrium with the individual samples. The albumin content of urine is proposed to be one important factor underlying poor reliability of direct radioimmunoassay. Both the immunoreactivity profiles observed after HPLC separation and the apparent 11-dehydro-TXB2-like immunoreactivity values determined by direct radioimmunoassay demonstrated that the unextracted urine contained a high ratio of interfering materials. It is concluded that efficient purification of human urine before determination is essential when this type of 125I-labelled radioligand is employed in radioimmunoassay.

Albumins↗

PubMedDate not supplied

Determination of 9alpha, 11beta prostaglandin F2 in human urine. combination of solid-phase extraction and radioimmunoassay.

This paper describes a new iodine-125 radioimmunoassay of 9alpha ,11beta-PGF2, and its use for the determination of urinary 9alpha,11beta-prostaglandin F2 after a selective one-step solid-phase extraction. The newly reported immunoassay is based on the use of 125I-tyrosyl methyl ester derivative of 9alpha,11beta-PGF2 and specific polyclonal antibody raised in rabbits. The assay detected as lowas 0.85 pg/tube 9alpha,11beta-PGF2, and the antibodyshowed lessthan 0.01 cross-reaction with PGF-ring metabolites (e.g., 8-iso-PGF2alpha, PGF2alpha 2,3-dinor-6-keto-PGF1alpha, and 5 more PGF-ring compounds). Both the intra-assay, and inter-assay CVs were lessthan 20% for internal controls containing low, medium and high concentrations of 9alpha,11beta-PGF2. Immuno-HPLC analysis showed a very low ratio of specific immunoreactivity in both non-extracted urine (6.5%), and in urine extracted on C18-silicacartridge (14.8%). By contrast, approximately 80% specific immunoreactivity could be achieved by using C2-silicaas the sorbent, acetonitrile: water (15:85, v/v) as wash solvent, and ethyl acetate as eluent of 9alpha,11beta-PGF2. This extraction procedure enabled a reasonably high extraction efficiency of 80.4 +/- 0.855 (mean +/- SEM, n=82), as determined by 3H-9alpha,11beta-PGF2. The new SPE/RIA method was applied for the determination of urinary 9alpha,11beta-PGF2 values in 50 healthy human volunteers. For the concentration and for the excretion rate 37.52 +/- 4.61 pg/ml (mean +/- SEM), and 3.50 + 0.35 ng/mmol creatinine (mean +/- SEM), respectively, was measured. The specificity of the SPE/RIA method was supported by the observed 69% decrease in 9alpha, 11beta-PGF2 excretion rate after acetylsalicylic acid treatment. The effect of nicotinic acid, a PGD2-stimulatory agent, was monitored by the urinary excretion of 9alpha ,11beta-PGF2 in 6 patients, by using the new SPE/RIA method. In patients responding with flushing symptoms nicotinic acid induced an increase of the urinary excretion of 9alpha,11beta-PGF2 in the range between 11% and 187%. In summary, the combination of the newly developed specific [125I] radioimmunoassay with solid-phase extraction on C2-silica cartridges enables the specific, sensitive, and reliable determination of 9alpha,11beta-PGF2 in human urine without the need for further laborious chromatographic purification before radioimmunoassay.

Adult↗