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Biomedical subjects

H Juan

Publications and source records attributed to H Juan.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of exogenous 5,8,11,14,17-eicosapentaenoic acid on cardiac anaphylaxis.

The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts were investigated. EPA dose-dependently inhibited the profound early coronary flow reduction after antigen injection. The less pronounced late phase of anaphylactic coronary flow reduction was, however, not significantly affected. EPA (15 X 10(-8) mol min-1) significantly shortened the average duration of antigen-induced arrhythmias. EPA dose-dependently decreased release of immunoreactive TXB2 and 6-keto-PGF1 alpha from anaphylactic guinea-pig hearts. Release of immunoreactive SP-LT was dose-dependently increased after antigen challenge in the presence of EPA. Inhibiton of the release of SP-LT by the lipoxygenase inhibitor esculetin (1 X 10(-7) mol min-1) was accompanied by a significant attenuation of flow reduction during the late phase of anaphylactic vasoconstriction. Reversed phase h.p.l.c. of perfusates from anaphylactic guinea-pig hearts revealed immunoreactivity comigrating with authentic leukotriene C4 (LTC4), LTD4, and LTE4. In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC5, LTD5 and LTE5. In addition to immunoreactivity migrating with LTB4, as observed in control heart perfusates, in perfusates from EPA-treated hearts, a second peak was observed, which coincides with the retention time described for LTB5. Exogenous LTC5 (1 X 10(-12) mol min-1 and 20 X 10(-12) mol min-1) induced dose-dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC4, but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC4 (20 X 10(-12) mol min-1) was dose-dependently inhibited by infusions of EPA. However, the negative inotropic effect of LTC4 remained unaffected. Thus, in the isolated anaphylactic heart of the guinea-pig exogenous EPA was effectively metabolized via the 5-lipoxygenase pathway whereas the cyclo-oxygenase pathway of polyunsaturated fatty acid metabolism was found to be inhibited. The results are in agreement with the suggestion that cyclo-oxygenase products are mediators of the early phase of the anaphylactic coronary constriction, while vasoconstrictor SP-LT are involved in the later phase. However, in spite of enhanced release of SP-LT, EPA infusion did not result in increased coronary constriction. Considering the fact that EPA antagonizes LTC4-induced coronary constriction, it seems possible, that EPA might act as a functional antagonist of vasoconstrictor eicosanoids including EPA-derived SP-LT.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Vasoconstriction induced by noradrenaline and angiotensin II is antagonized by eicosapentaenoic acid independent of formation of trienoic eicosanoids.

The isolated perfused rabbit ear was used to investigate the effect of eicosapentaenoic acid (EPA) on the vasoconstriction induced by noradrenaline (NA) and angiotensin II (A II). EPA (0.1, 1.0, 10.0 micrograms/ml) was shown to reduce the vasoconstriction (inhibition of flow) induced by NA in a dose-dependent manner. The dose-response curves of NA were shifted to the right. Emax of NA was reduced in particular at the highest concentration of EPA. The maximum effect of EPA developed slowly and reached a steady state after 150 min (0.1 microgram/ml EPA), 120 min (1.0 microgram/ml EPA), 100 min (3.0 microgram/ml EPA) and 60 min (10 micrograms/ml), respectively. In the presence of indomethacin (3 micrograms/ml), the vasoconstrictor effect of NA was not significantly influenced. The effect of EPA (3 micrograms/ml) was not reduced by indomethacin. In the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 micrograms/ml), the vasoconstrictor effect of NA was not significantly influenced. The effect of EPA (3 micrograms/ml) was not reduced by NDGA. Concomitant addition of indomethacin (3 micrograms/ml) and NDGA (10 micrograms/ml) also did not reduce the effect of EPA. EPA (3.0, 10.0 micrograms/ml) was shown to reduce also the vasoconstrictor effect of A II in the absence and the presence of the cyclooxygenase and lipoxygenase inhibitors. Determination by radioimmunoassay showed that the levels of thromboxane B2 (TXB2)-like immunoreactivity were below the detection limit in the perfusate of the ear. The levels of 6-keto-PGF1 alpha- and PGE2-like immunoreactivity in the perfusate were low. EPA reduced the concentration of 6-keto-PGF 1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Influence of Epilobium extracts on prostaglandin biosynthesis and carrageenin induced oedema of the rat paw.

Epilobium species have been used as remedies in folk-medicine for the treatment of pathophysiological processes of the prostata. In this paper the influence of extracts of Herba Epilobii angustifolii L. and Herba Epilobii parviflori Schreb. on prostaglandin biosynthesis and the carrageenin rat paw oedema is described. Aqueous extracts of Herba E. angustifolii reduced the release of prostaglandins I2, E2 and D2 (in the perfused rabbit ear) approximately 5 times more effectively than did similar extracts of Herba E. parviflori. Methanolic extracts were inactive. The aqueous extract of E. angustifolium strongly reduced the carrageenin-induced rat paw oedema whereas that of E. parviflorum was inactive. The chemical nature of the active compound(s) is as yet unknown but flavonoids and sitosterol derivatives can be excluded.

Animals↗
PubMed1985

Eicosapentaenoic acid inhibits the release of 14C-prostacyclin from a perfused tissue after incorporation of 14C-prostaglandin precursors.

The isolated rabbit ear was labeled by perfusion either with 14C-arachidonic acid (AA) or 14C-dihomo-gamma-linolenic acid (DGLA). The influence of unlabeled eicosapentaenoic acid (EPA) on the release and metabolism of the labeled prostaglandin (PG) precursors was studied with the aid of radio-thin-layer-chromatography (TLC). After incorporation of 14C-AA, the ionophore A 23187 (10 micrograms) stimulated the release of products comigrating on TLC plates with authentic PGI2 (measured as 6-keto-PGF1 alpha), PGE2, PGD2 and AA. In unlabeled ears, A 23187 (10 micrograms) stimulated the release of PGI2 and PGE2 (determined by radioimmunoassay) in similarly relative amounts as found for the labeled products. The release of PGD2 was not measured. After incorporation of 14C-DGLA, A 23187 (10 micrograms) stimulated the release of labeled products comigrating in several TLC-systems with 6-keto-PGF1 alpha (but not PGF1 alpha), PGE1, PGD1 and DGLA. After incorporation of 14C-AA, infusion of unlabeled EPA (0.1, 1 and 10 micrograms/ml) reduced the release of 14C-PGI2 but not of the other bisenoic PGs. Furthermore, in ears labeled with 14C-DGLA, EPA strongly reduced the release of a product comigrating with 6-keto-PGF1 alpha and to a lesser extent of a product comigrating with PGE1. Infusion of unlabeled EPA (1 and 10 micrograms/ml) did not reduce the release of 14C-AA or 14C-DGLA indicating that a phospholipase A2 was probably not inhibited by EPA. It is concluded that EPA inhibits PGI2 synthase rather than cyclooxygenase since after incorporation of 14C-AA, only the release of PGI2 is reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Influence of a diet rich in eicosapentaenoic acid on the development of rat paw oedema and on the formation of prostaglandins I2 and E2.

The influence of feeding a marine oil (MaxEPA) with a high content of eicosapentaenoic acid (EPA) to rats for 10 weeks on the development of carrageenin oedema was studied. Since prostaglandins (PGs) are involved in the development of this acute experimental inflammation, the influence of EPA feeding on PG release from aorta (PGI2) and from the subplantar skin of the inflamed foot (PGI2, PGE2) was investigated also. MaxEPA was fed in two daily doses containing 50 or 100 mg EPA/kg/day. In both rat groups there was no influence of EPA on the development of the oedema. However, the capacity of aorta and skin of the plantar region of the experimentally inflamed foot to release PGI2 was strongly reduced by EPA. On the other hand, the release of PGE2 from the skin was not reduced. Indomethacin at a low dose (2 mg/kg perorally) reduced the development of the paw oedema as well as the release of PGs in control rats and rats on an EPA-containing diet. It is concluded that EPA did not influence carrageenin oedema because there was an adequate production of the oedema promoting substance PGE2.

Animals↗
PubMed1985

Dihomo-gamma-linolenic acid increases the metabolism of eicosapentaenoic acid in perfused vascular tissue.

The isolated rabbit ear was perfused with 14C-arachidonic acid (AA), with 14C-eicosapentaenoic acid (EPA) or with 14C-dihomo-gamma-linolenic acid (DGLA). After incorporation of 14C-AA, the ionophore A 23187 (10 micrograms) stimulated the release of products comigrating with authentic PGI2 (measured as 6-keto-PGF1 alpha), PGE2 and PGD2 on the thin layer chromatography plate. After incorporation of 14C-EPA, A 23187 did not release any trienoic 14C-PGs. After incorporation of 14C-DGLA, A 23187 stimulated the release of labeled products comigrating with 6-keto-PGF1 alpha (but not PGF1 alpha), PGE1 and PGD1. Infusion of unlabeled AA (1 and 10 micrograms/ml) did not influence the metabolism of 14C-EPA or 14C-DGLA. Infusion of unlabeled DGLA (10 micrograms/ml) strongly stimulated the release of trienoic 14C-PGs but did not significantly increase the release of bisenoic 14C-PGs. Neither DGLA nor AA influenced the release of any other labeled incorporated PG precursor, indicating that a phospholipase A2 was not affected. The results show that DGLA is able to stimulate the metabolism of incorporated 14C-EPA resulting in an increased release of antiaggregatory trienoic PGs. The mechanism of this effect is unclear but it may be mediated via the formation of a hydroperoxide derivative of DGLA. Thus, an increased generation of antithrombotic trienoic PGs may be expected under special conditions, possibly also in vivo, depending on the supply of unsaturated fatty acids or the level of various hydroperoxide derivatives.

8,11,14-Eicosatrienoic Acid↗
PubMed1984

Prostaglandin release and nociceptor stimulation by peptides.

The effects of substance P, somatostatin, vasoactive intestinal polypeptide, cholecystokinin octapeptide, eledoisin and bombesin on release and metabolism of incorporated (1-14C)-arachidonic acid was investigated in the isolated rabbit ear. The influence of eledoisin and bombesin on release of prostaglandins was compared with that of bradykinin (Sametz and Juan 1982). Only eledoisin and bombesin stimulated the release of prostaglandins I2 and E2 but with a lesser potency than bradykinin. Only eledoisin in a high dose stimulated nociceptors per se whereas bombesin did not. Eledoisin and bombesin in a low dose enhanced nocicpetion induced by acetylcholine in the rabbit ear; this enhancement of the algesic effect of acetylcholine was abolished by indometacin which indicates a sensitization of nociceptors by released prostaglandins. Although effects of eledoisin and bombesin are mediated at least in part by released prostaglandins, the nociceptor-stimulating and prostaglandin-releasing potency of bradykinin remaines unique among all peptides tested so far.

Animals↗
PubMed1984

Prostaglandin determination with fluorescent reagents.

Fluorescent derivatives of PGE2 as a model substance were formed with naphthyl isocyanate, anthracene isocyanate, 4-(6-methyl- benzothiazol -2-yl)phenyl isocyanate, benzocoumarin -3-carboxylic acid chloride and 4-bromomethyl-7- methoxycoumarin . The optimum conditions for derivatization with these reagents were investigated and the results were compared. Quantitative determination was performed by means of fluorodensitometric measurement of the derivatives. Using 4-bromomethyl-7- methoxycoumarin as a reagent as little as 100 pg of the PGE2 derivative can be detected.

Chemical Phenomena↗
PubMed1984

[The pharmacology of gold compounds].

Parenterally administered gold compounds have been used for decades for treatment of rheumatoid arthritis. The new gold compound triethylphosphine gold (auranofin) can be partially absorbed in the gut following oral administration due to its higher lipophilic nature. This is probably also the main cause for the differences in kinetic properties versus the parenteral gold compounds. Following administration of auranofin, there are lower concentrations of gold in blood and organs; 95% of the gold is excreted in feces whereas 70% of gold, following gold sodium thiomalate, is excreted in the urine. These differences have consequences for the mode of adverse reactions. A common property of all gold compounds, however, is the relative distribution in organs. The highest concentrations of gold were found in the reticuloendothelial system, in liver, kidney and spleen, followed by joints. The mode of action of gold compounds is still unexplained. They inhibit some types of experimental inflammation and the activity of various cells involved in inflammatory processes. In some cases auranofin exerts a higher influence. Following incorporation of gold in lysosomes, the impairment of macrophage function appears to be most important. This effect probably influences (indirectly) the immune system since macrophages interact with T- and B-lymphocytes. The significance of these findings for the therapeutic effect of gold compounds is, however, not known. The rate of undesirable effects of gold compounds is very high requiring exact supervision during chrysotherapy. Mucosal and cutaneous reactions are very frequent, followed by proteinuria, diarrhea and thrombocytopenia. Bone marrow aplasia is most serious but relatively rare.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

[Recently discovered mechanisms of action of non-steroidal antirheumatic agents: possible, not only symptomatic therapeutic effects].

Non-steroidal antirheumatic agents are assumed to exert their therapeutic effects by inhibiting biosynthesis of prostaglandins at the level of cyclo-oxygenase. This effect leads to a reduction of inflammatory symptoms caused or potentiated by prostaglandins. Recently, some new further effects (partly also induced by inhibition of prostaglandin synthesis) of non-steroidal antirheumatic drugs have been discovered. These effects influence functions and interactions of white blood cells involved in pro-inflammatory and immunological processes, and appear to be causal rather than symptomatic. Furthermore, there are differences in the mode of action of some antirheumatic agents, in particular with regard to inhibition of generation of inflammatory superoxide anions.

Anti-Inflammatory Agents↗
PubMed1983

[Preliminary results of prostaglandin E1 therapy in peripheral obliterating arteriopathy].

Prostaglandin E1 was given intraarterially to twenty persons with severe peripheral ischaemia at risk of requiring amputation of a limb for ischaemic ulcers or necrosis. All patients had received conventional therapy without success before PG E1 treatment. An average dose of 6.14 ng/kg/min of PG E1 was given intraarterially for 2 hrs daily over a period of six days. In fifteen cases PG E1 therapy resulted in complete or partial healing of the ulcers and necrotic areas while the patients no longer suffered from pain at rest. No beneficial effects of PG E1 treatment were seen in five patients. In these cases cases multiple arterial occlusions, caused by arteriosclerosis and diabetes mellitus, existed, in more than three levels. Side effects like pain in the infused limb and swelling of the extremity occurred in fourteen patients, but were reversible in each case.

Alprostadil↗
PubMed1983

Uptake, stimulated release and metabolism of (1-14C)-eicosapentaenoic acid in a perfused organ of the rabbit.

The isolated rabbit ear was prelabeled by perfusion with (1-14C)-eicosapentaenoic acid (EPA). Uptake and distribution in lipids, basal release and, in particular, stimulated release and metabolism was studied. In a series of experiments a comparison with results obtained by labeling the perfused organ with (1-14C)-arachidonic acid (AA) was made. Approximately 80% of the perfused labeled EPA was incorporated into the tissue. The main peak (74% of the incorporated radioactivity) was found in the phospholipids. Following incorporation of labeled EPA, basal release of EPA but ot of trienoic prostaglandins (PGs) could be observed. Bolus injection of bradykinin (3 micrograms) and the calcium-ionophore A23187 (10 micrograms) led to an immediate increased release of radioactivity in the effluent which declined within 10--20 min. Analysis of the extracted effluent by thin layer chromatography (TLC) showed that only the release of EPA and of radioactivity at the Rf-value of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) was increased following stimulation by bradykinin and A23187. No labeled trienoic PGs could be detected. Upon injection of A23187 in the presence of indomethacin (3 micrograms/ml) there was no reduction of any peak of radioactivity on the TLC-plate, indicating that no cyclooxygenase product of EPA was generated. The extremely high dose of 10 micrograms bradykinin or 50 micrograms A23187 led to a small release of labeled PGI3 (A23187) and to a somewhat higher release of labeled PGE3 (bradykinin, A23187). In some experiments release and metabolism of labeled EPA were compared with those of labeled AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗