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Biomedical subjects

J E Vincent

Publications and source records attributed to J E Vincent.

At least 37 records · Page 2Linked to original sources
PubMed1986

Opposite effects of adrenalectomy on eicosanoid release in rat peritoneal macrophages and spleen.

The effect of adrenalectomy on the formation of cyclo-oxygenase and lipoxygenase products by activated peritoneal rat macrophages was determined and compared with that of the spleen. After isolation, the cells and tissues were incubated with [1-14C] arachidonic acid and the Ca-ionophore A23187 and the metabolites isolated by HPLC chromatography. The main components formed in the macrophages of the controls are 6-keto-PGF1 alpha, TxB2 and 12-HETE. One peak represents 5, 12 di HETE. Smaller amounts of PGF2 alpha, PGE2, PGD2, LTB4 and 15-HETE are also present. After adrenalectomy, a considerable increase occurs in the amounts of LTB4, 15-HETE and 12-HETE. The increase in the PG is smaller. The compounds formed from endogenous arachidonic acid are also determined. In the cells of the controls, the formation of LTB4 is considerably increased after adrenalectomy. In the spleen, PGD2 and 12-HETE are decreased after adrenalectomy. The effect of the macrophages is most probably related to a diminished amount or inactivation of lipocortin, a glucocorticosteroid induced peptide with PlA2 inhibitory activity in adrenalectomized animals. In the decrease in formation in the spleen, the absence of the permissive effect of glucocorticosteroids on the hormone-induced lipolysis may play a role.

Adrenalectomy↗
PubMed1986

Increase in the formation of cyclooxygenase and lipoxygenase products in kidneys of adrenalectomized rats.

The effect of adrenalectomy on the formation of cyclooxygenase and lipoxygenase products from [1-14C]-arachidonic acid in rat kidneys after incubation with the Calcium-ionophore A23187 has been determined. The metabolites were isolated by HPLC. The main components formed are PGD2, PGE2, PGF2 alpha, LTB4, 5,12 di-HETE and 5-, 12- and 15-HETE. After adrenalectomy, an increase occurs in the formation of PG and LT, which is highest in that of PGD2 and 12-HETE. These effects are most probably related to a diminished formation or inactivation of lipocortin in adrenalectomized animals, a glucocorticosteroid induced peptide with phospholipase A2 inhibitory activity.

Adrenal Glands↗
PubMed1986

Sotalol potentiates the leukotriene C4-induced contractions and thromboxane A2 release of guinea pig lung parenchymal strips.

The leukotriene C4 (LTC4)-induced contraction and thromboxane A2 (TxA2) release of the guinea pig lung parenchymal (GPLP) strip are both inhibited by the beta 2-adrenergic agent salbutamol. The effect of LTC4 is restored to nearly normal by the beta-adrenergic antagonist sotalol. The latter substance alone also induces a contraction in the GPLP strip and potentiates the contractions and the TxA2 release of LTC4. During the sotalol-induced contractions, no TxA2 release occurs. An antihistaminic, mepyramine had no effect on the sotalol-induced contraction. When sotalol is added repeatedly to a GPLP strip, only the first time a contraction occurs.

Animals↗
PubMed1985

Incorporation into the tissues and turnover of arachidonic acid after administration to normal and essential fatty acid deficient rats.

A comparison was made of the incorporation into the tissues and metabolism of [1-14C] arachidonic acid (AA) after i.v. administration to normal and EFA-deficient rats. At different times, ultra-thin whole body sections were prepared and the distribution of the radioactivity determined by autoradiograms. After 5 min, a considerable incorporation occurs in the following organs: subcutaneous and perispinal fat, liver, heart muscle, kidney and adrenal. The EFA deficient rats show a similar distribution but the radioactivity is longer retained. The total amount of radioactivity in the heart, liver, kidney and adrenal was measured at different times. A decline occurs in the heart, and an increase in the adrenal. In the urine, the highest amount of radioactivity is excreted on the first day. The excretion is lower in the EFA-deficient rats. Small amounts of radioactive metabolites with the chromatographic characteristics of PGE2 and 13,14 dihydro-15ketoPGE2 were isolated from urine. The amounts of 14CO2 produced were determined after the administration of [1-14C] AA. Half times were: 39 +/- 2.9 min in the EFA-deficient and 28 +/- 2.8 min in the normal rats. In the heart, AA is incorporated into phospholipids and neutral lipids. The following percentages were determined: phosphatidylinositol: 6.9 +/- 0.6%, phosphatidylcholine: 44 +/- 4.1%, phosphatidylethanolamine: 10.0 +/- 1.0%, neutral lipids: 9.3 +/- 1.6%. Several explanations can be given for the higher requirements of some tissues for AA. It could be, that this substance is used in the formation of particular membranes with a high AA content. Differences in the amounts of metabolites produced may also play a role.

Animals↗
PubMed1985

Production of leukotrienes and prostaglandins by human ascites cells.

Ascites was collected from six patients with liver cirrhosis and the cells isolated. These cells, mainly macrophages, were labelled with 14C-arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by HPLC. The main substances formed by the ascites cells were leukotriene B4, 5-hydroxy-6,8,11,14 eicosatetraenoic acid and leukotriene C4. Smaller amounts of thromboxane B2, 12-hydroxy-5,8,10 heptodecatrienoic acid and 6-keto-prostaglandin F1 alpha were isolated. Human peritoneal macrophages are therefore capable of producing leukotrienes and prostaglandins. Production of these substances might play a role in some of the complications of patients with liver cirrhosis and ascites.

Arachidonic Acid↗
PubMed1984

Determination of leukotrienes and prostaglandins in [14C] arachidonic acid labelled human lung tissue by high-performance liquid chromatography and radioimmunoassay.

A liquid chromatographic method for the determination of 14C-labelled prostaglandins, leukotrienes and other lipoxygenase products formed by human lung tissue is described. In this paper we report our problems identifying these substances when 3H- or 14C-labelled compounds are compared with measurements of the mass by absorption or radioimmunoassay. Furthermore, some preliminary results of [14C] arachidonic acid labelled human lung tissue, stimulated by the Ca-ionophore A23187, show that, of the lipoxygenase products, mostly leukotriene B4 like compounds are formed and less leukotriene C4, E4 and D4. Relatively large amounts of hydroxyeicosatetraenoic acids are present. The main cyclooxygenase products are thromboxane B2, 6-ketoprostaglandin F1 alpha and prostaglandin D2.

Arachidonic Acid↗
PubMed1984

The effects of leukotrienes, thromboxane A2 and phospholipase A2 on human, porcine and guinea pig lung parenchyma.

A comparison was made of the contractions, induced by LTD4, histamine and phospholipase A2 in parenchymal strips of guinea pig (GPLP), porcine and human lung in a cascade superfusion system. The effects of LTD4 and phospholipase A2 on the release of TxA2 in these tissues and of TxA2, 5-HT and acetylcholine on the GPLP were also determined. In the GPLP strip, the LTC4-induced contractions are due for +/- 80% to the release of TxA2 and for +/- 20% to the direct effect of LTC4. The guinea pig tissue displayed the highest sensitivity towards all substances, except to the contraction induced by histamine, which was most effective in the porcine tissue. Low activities were found in the human tissue in all tests. The reason for these effects may be a difference in activities or number of cell types which participate in the reactions leading to the contractions.

Aged↗
PubMed1984

Determination of the ratio of the contractions, induced by thromboxane A2 in the guinea pig lung parenchymal strip after exogenous administration and formation in the tissue.

A comparison was made of the contractile effects of exogenously added and endogenously formed TxA2 on guinea pig lung parenchyma. Aggregating platelets were used as a source of exogenous TxA2. After the addition to the lung strip, the contractions were measured. Endogenous formation of TxA2 was induced by adding either 1 micrograms P1A2 or 50 ng LTD4 to the strip. It was found that the ratio of potency of action of endogenous/exogenous TxA2 was 5.1 +/- 0.62 for P1A2 and 5.0 +/- 1.3 for LTD4.

Animals↗
PubMed1984

The effect of 5-(2-chlorobenzyl)-5,6,7,7a-tetrahydro 4H-thieno (3.2-C)-pyridine-2-one hydrochloride (PCR 3787), a metabolite of ticlopidine, on the aggregation of human platelets in vitro and on the aggregation inhibiting action of PGI2 and PGD2.

A metabolite of ticlopidine, PCR 3787, in concentrations from 25-200 micrograms/ml inhibited the aggregation of human platelets, induced by different amounts of collagen. The effect of PCR 3787 on PG formation was tested in rat platelets. After incubation with PCR 3787, platelets were labelled with 1-14C arachidonic acid and aggregation induced with collagen. The sum of the PG formed (PGF2 alpha + PGE2 + PGD2) was higher in the platelets incubated with PCR 3787 than in the controls. The aggregation-inhibiting effects of PGI2 (1 ng/ml) and PGD2 (10 ng/ml) on human platelets were enhanced by the addition of PCR 3787 (100 micrograms/ml). A stable derivative of PGI2, ciloprost was used. These results indicate, that part of the aggregation-inhibiting effect of ticlopidine can be attributed to the formation of this metabolite.

Collagen↗
PubMed1984

The effect of inhibitors on the LTD4-induced contractions and release of thromboxane A2 in the guinea pig lung parenchymal strip.

The guinea-pig lung parenchymal (GPLP) strip is sensitive to leukotrienes (LT) C4 and D4 (LTC4 and LTD4). These substances induce contractions during which thromboxane (TX) A2 (TxA2) is released. This event was measured both by bioassay of TxA2 and radioimmunoassay of thromboxane B2 (TxB2). Indomethacin partially inhibited the contractile response and completely abolished the release of TxA2. The proportional participation of TxA2 in the contractile response was calculated quantitatively, and appeared to be 70-90%. On basis of these results, it is concluded that only a small proportion of the contractions is due to the direct action of the leukotrienes and a major part to the formed thromboxane A2. The action of the phospholipase A2 (PLA2) inhibitor chloroquine and the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), were measured both on the contraction and the TxA2 release. Chloroquine in a dose of 40 /micrograms/ml totally inhibited the TxA2 release induced by 50 ng LTD4. At higher doses, the contractions were also completely inhibited. IBMX in a dose of 22 /micrograms/ml inhibited both the contraction and the TxA2 release to a large extent. These effects are most probably due to an inhibition of the phospholipase A2 which is activated by the leukotrienes. It is supposed that chloroquine acts directly and that the action of IBMX is due to an increase in cyclic AMP, which also leads to an inhibition of the enzyme. After the incubation of lung strips with [1-14C] arachidonic acid (AA), mainly TxB2 and lipoxygenase products are formed.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Correlation between the distribution of 3H-labelled enkephalin in rat brain and the anatomical regions involved in enkephalin-induced seizures.

The correlation between the distribution of the intraventricularly (i.v.t.) administered delta agonist [3H](D-ala2,D-leu5)-enkephalin ([3H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [3H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 microns. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of delta opiate receptors, localized within the first 100 microns of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.

Animals↗
PubMed1983

Separation of the two components of the contractile activity of leukotriene C4 on the guinea pig lung parenchymal strip.

The contractions, induced by LTC4 in the guinea pig lung parenchymal strip are composed of two parts, one of which is due to the effect of the released TxA2 and the other one to the direct action of LTC4. After the addition of indomethacin, the TxA2 release is totally inhibited, but the contractions only partly. It is shown that the release of TxA2 only occurs during the initial period of the contractions. This indicates that the direct action of LTC4 represents the slow acting component in the contraction.

Animals↗
PubMed1983

Raised plasma thromboxane B2 levels in alcoholic liver disease.

In experimental animals endotoxin administration causes increased levels of thromboxane B2 and prostaglandins. Liver cirrhosis is often complicated by endotoxemia. In sixteen patients with alcoholic liver cirrhosis, we measured plasma thromboxane B2 levels. In twelve patients we found on one or more occasions raised plasma thromboxane B2 levels. Raised plasma thromboxane B2 levels were associated with significantly higher serum levels of urea, alkaline phosphatase, gamma glutamyl transpeptidase and lower antiplasmin and antithrombin III levels. It is possible that some of the complications in patients with alcoholic liver cirrhosis are mediated by thromboxanes.

Adult↗
PubMed1983

Raised plasma levels of thromboxane B2 in systemic mastocytosis.

Plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in six patients with systemic mastocytosis. Patients with systemic mastocytosis had significantly higher plasma thromboxane B2 levels (530 +/- 105 pg/ml, mean +/- SEM) than controls (118 +/- 8.2 pg/ml, P less than 0.001) and significantly lower 6-keto-prostaglandin F1 alpha levels (40 +/- 3.1 pg/ml, mean +/- SEM) than controls (49 +/- 1.6 pg/ml, P less than 0.05). The mechanism of the raised plasma thromboxane B2 levels is not clear. One possible explanation is that the high thromboxane levels are secondary to an increased production of leukotrienes C and D, which are constituents of slow reacting substances of anaphylaxis.

6-Ketoprostaglandin F1 alpha↗