PubMed Health⌕ Search

Biomedical subjects

B A Peskar

Publications and source records attributed to B A Peskar.

At least 91 records · Page 5Linked to original sources
PubMed1990

Afferent nerve-mediated protection against deep mucosal damage in the rat stomach.

Intragastric capsaicin protects against ethanol-induced gross mucosal lesion formation by stimulation of afferent nerve endings in the rat stomach. The aims of the present study were to examine histologically the protective effect of capsaicin and to test whether this effect is related to changes in mucosal eicosanoid formation and mucosal blood flow. Intragastric capsaicin (160 microM) significantly reduced gross mucosal lesion formation induced by 25% ethanol. Light microscopy revealed that the depth of erosions was attenuated likewise. However, capsaicin did not prevent ethanol from causing superficial damage to the mucosa as observed by light and scanning electron microscopy. The protective action of capsaicin against ethanol remained unchanged by a dose of indomethacin that reduced the ex vivo formation of prostaglandin E2 and 6-oxo-prostaglandin F1 alpha in the gastric mucosa by about 90%. Capsaicin alone did not affect the ex vivo formation of these prostaglandins and of leukotriene C4. Intragastric capsaicin (160 microM) enhanced gastric mucosal blood flow by 89% as measured by the hydrogen gas clearance technique. This effect was also observed when capsaicin was administered together with 25% ethanol. These data indicate that afferent nerve stimulation by intragastric capsaicin protects against deep mucosal damage in response to ethanol, an effect that seems related to an increase in mucosal blood flow but not to eicosanoid formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Impaired conversion of exogenous arachidonic acid by platelets to thromboxane B2 and correction of that deficiency by interferon-alpha.

In the course of an investigation of cyclooxygenase and 12-lipoxygenase activity in platelets of patients with myeloproliferative syndrome receiving treatment with interferon-alpha 2 patients showed unusual results which have not been reported so far. Both patients had thrombocytosis, in one case associated with polycythaemia. In platelets of both patients, a reduced conversion of exogenous 14C arachidonic acid to TXB2 was observed accompanied by a shift in conversion to PGE2 and 12-HETE in one patient and to 12-HETE alone in the other before therapy. These findings were paradoxically associated with evidence of enhanced platelet activation in vivo. Treatment of both patients with interferon-alpha resulted in reversal of the biochemical abnormalities and in clinical remission.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Defects in the prostaglandin-system--heredity, prevalence and vascular risk analysis.

2180 healthy adults, 620 patients (90% with cardiovascular disease, 10% others), 143 newborns and 351 relatives of persons in whom any abnormality of the prostaglandin (PG)-system had been discovered were involved in the Viennese Initiative for Prostaglandin (VIP)-Screening from 1984 through May 1989. The defects discovered were either inborn or acquired ones and were either familial or non-familial. The highest number of defects (54.8% of the total) identified were associated with PGI2. They indicated a lack of the PGI2-synthesis stimulating plasma factor (PF)-activity (n = 17) and PGI2-stabilizing capacity in plasma (defect 'Vienna-Döbling', n = 4, 12.9% of total), absence of high-affinity PGI2-binding sites on platelet membranes and lack of response of platelets to PGI2 (defect 'Vienna-Hietzing', n = 2, 6.5% of total). Furthermore, a lack of cyclooxygenase (n = 2, 6.5% of total), 12-lipoxygenase (defect 'Vienna-Penzing', n = 3, 9.7% of total) and thromboxane synthetase (n = 3, 9.7% of total) activities were diagnosed. In newborn screening, the PF-absence amounted to 2.8% (4/143), the lack of PGI2-stabilizing capacity to 0.7% (1/143). In adults, the prevalence is difficult to assess. Nevertheless, our findings indicate a frequency of 0.93% (26/2800) of defects in the PG-system among the adult Viennese population. The lack of PF-activity seems to be by far the most frequent one (0.46%, 13/2800). Other defects are much less common. It is not clear whether the incidence in healthy subjects or in patients with cardiovascular disease is different from each other. Further, it remains to be assessed whether there is a causative relation to vascular events or just an association. More intensive screening activities should validate the diagnostic, pathogenetic and therapeutic impact of the various defects in the PG-system.

Adult↗
PubMed1990

Identification and characterization of cysteinyl-leukotriene formation in tissue slices from human intracranial tumors: evidence for their biosynthesis under in vivo conditions.

In previous studies, it had been shown that human gray and white matter tissue slices have the capacity to synthesize large amounts of cysteinyl-leukotrienes (cysteinyl-LT) in vitro. This study was initiated to investigate cysteinyl-LT formation by tissue slices from intracranial tumors in comparison with cyclooxygenase products such as prostaglandin (PG) F2 alpha and thromboxane (TX) B2. Tissue slices from meningiomas and astrocytomas were found to release large amounts of cysteinyl-LT spontaneously and even higher amounts after ionophore A 23187 stimulation, which could not be accounted for by blood possibly remaining in the tissue slices. Cysteinyl-LT were identified by their immunoreactive characteristics, their biological activity in the guinea pig ileum bioassay, and their retention time on reversed-phase HPLC. With increasing malignancy, astrocytomas were shown to have an increasing biosynthetic capacity for cysteinyl-LT and TXB2 in vitro. In comparison with meningioma patients, malignant astrocytoma patients had an enhanced urinary excretion of LTE4, the major urinary metabolite of cysteinyl-LT in humans, which dropped in level within 7 days after operation by 79%. A correlation exists between the in vivo cysteinyl-LT production in patients with malignant astrocytomas and that observed under basal conditions in the tissue slices in vitro. The results provide evidence that in malignant astrocytoma patients, the tumor tissue produces large amounts of cysteinyl-LT, which may be detected in the patients' urine.

Astrocytoma↗
PubMed1989

Response of thromboxane B2, malondialdehyde and platelet sensitivity to 3 weeks low-dose aspirin (ASA) in healthy volunteers.

To examine the effects of low-dose aspirin thromboxane B2 (TXB2), malondialdehyde (MDA) and platelet sensitivity to prostaglandin I2 (PGI2) have been measured in a total of 18 healthy volunteers. They were randomly assigned to 3 groups, 6 volunteers each, receiving either 1, 10 or 20 mg ASA orally a day for 3 weeks in a double-blind fashion. In order to assess the time course of ASA-induced changes, blood was drawn before, 1 hour and 2, 3, 5, 7, 9, 12, 14, 16 and 21 days after the first drug-intake. Serum-TXB2 was depressed time- and dose-dependently, after 1 mg daily to about 60%, after 10 mg to about 30%, after 20 mg to about 5% of controls. MDA-formation and conversion of exogenously added arachidonic acid (AA) to TXB2 also dropped significantly, (p less than 0.01), the extent depending on the ASA-dosage administered. The drop in MDA- and TXB2-values in the 3 groups correlated with r = 0.98, 0.94, 0.98, respectively. The platelet sensitivity during 20 and 10 mg ASA-administration did not change at all, whereas a significant increase (p less than 0.01) in platelet sensitivity during treatment with 1 mg ASA was observed.

Adult↗
PubMed1989

The effects of platelet-activating factor on flow rate and eicosanoid release in the isolated perfused rat gastric vascular bed.

In the isolated rat stomach perfused via the vasculature in situ under constant pressure bolus injections of platelet-activating factor (PAF, 3, 16, or 50 ng) induced dose-dependent, long-lasting reductions of flow rates and simultaneously significant increases in the release of cysteinyl-leukotrienes (cys-LT), thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha. Reversed phase high pressure liquid chromatography demonstrated the release of a mixture of comparable amounts of LTC4, LTD4 and LTE4 by PAF. Inhibition of cys-LT synthesis by the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and L-651,896 did not significantly affect PAF-induced flow reduction indicating that endogenous cys-LT are of minor importance for the PAF effect on gastric vascular flow. This conclusion is supported by the fact that the cys-LT receptor antagonist FPL 55712 in a concentration (1 x 10(-6) M) that completely antagonized gastric flow reduction by exogenous LTC4 (1 x 10(-7) M) had no effect on the PAF-induced reduction of flow. The cyclooxygenase inhibitor indomethacin aggravated the PAF-induced flow reduction suggesting that the endogenous vasodilator PGI2 might act as a functional PAF antagonist in the rat gastric vascular bed. In contrast to FPL 55712 the PAF antagonist BN 52021 significantly and concentration-dependently antagonized the PAF effect on gastric vascular flow. The results demonstrate that PAF and LTC4 induce flow reductions in the rat gastric vascular bed by activating different receptors and that endogenous eicosanoids released by PAF do not contribute significantly to the PAF effect on gastric vascular flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

[Defects in the prostaglandin system. VIII. A pathologic thrombocyte population in myeloproliferative syndrome, which forms no thromboxane from exogenous arachidonic acid].

In 2 out of 29 patients suffering from the myeloproliferative syndrome a lack of thromboxane conversion by platelets from exogenous arachidonic acid was discovered. In one patient PGE2 (30.9%) and 12-HETE (12-Hydroxyeicosatetraenoic acid) (42.8%) were formed instead, whilst in the other patient 12-HETE (72.9%) was the main metabolic product. In both the patients, serum and plasma TXB2, as well as malondialdehyde, were quite low. It is claimed that this phenomenon is due to the expression of a pathological population of platelets related to the disease.

Aged↗
PubMed1988

[Collection, preparation and storage of human plasma for radioimmunologic determination of thromboxane B2].

There are at present several methods available for the quantitative determination of thromboxane B2. However, they give results differing in precision and biological information. If it were possible to exclude sampling and storage artefacts, radioimmunological plasma thromboxane B2 measurement would be the method of choice for routine clinical determinations. The optimum conditions for processing the plasma for such purposes were assessed in 10 healthy volunteers (6m, 4f, 24-37a). They include a 30-minute resting period before blood sampling, constant needle diameter, blood withdrawal without venous occlusion, proper anticoagulation and cyclooxygenase inhibition. Storage at -70 degrees C for less than 2 weeks and the avoidance of repeated freezing and thawing are further prerequisites. In contrast to widely-held opinion, the plasma levels of thromboxane B2 obtained using these precautions are of practical value, roughly comparable to those employing the platelet proteins beta-thromboglobulin and platelet factor 4. However, practically speaking determinations are limited to a small number of carefully handled samples. Hence, the method cannot be unreservedly applied to daily routine clinical use.

Blood Platelets↗
PubMed1988

Formation of cysteinyl-leukotrienes by human brain tissue.

Using sensitive radioimmunoassay techniques, the formation of cysteinyl-leukotrienes (LT) and prostaglandin (PG) F2 alpha was investigated in human brain tissue slices in vitro. Under basal conditions spontaneous release of considerable amounts of LTC4-like material and PGF2 alpha could be detected from slices of both human grey and white matter. Ionophore A23187 stimulated the release of large amounts of LTC4-like material while leaving unaffected the formation of the cyclo-oxygenase product PGF2 alpha. Incubation of grey or white matter in the presence of the cyclo-oxygenase inhibitor indomethacin inhibited the release of PGF2 alpha but did not affect that of LTC4-like material. Preincubation of brain tissue in the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished the ionophore A23187-induced release of LTC4-like material from both grey and white matter and also significantly reduced the spontaneous release of LTC4-like material from white matter slices. Formation of PGF2 alpha was not affected by NDGA. Using the isolated guinea pig ileum the LTC4-like material was shown to possess biological activity which could be antagonized with the slow-reacting substance of anaphylaxis (SRS-A) antagonist FPL 55712. By reversed phase HPLC the immunoreactive LTC4-like material from human grey matter was shown to coelute with authentic LTC4, LTD4 and LTE4, while material from human white matter coeluted with authentic LTD4 and LTE4. The capacity of human brain tissue to synthesize cysteinyl-LT may be important for cellular functions in the central nervous system.

Brain↗
PubMed1988

[Fibrinolytic activity, thrombocyte function and pharmacokinetics during intra-arterial or intravenous prostaglandin E1 infusion in patients with chronic arterial occlusive disease].

Monitoring various parameters of fibrinolytic activity in 6 patients with arterial occlusive disease during intra-arterial (i.a.) or intravenous (i.v.) prostaglandin (PG) E1 infusions indicated activation of the endogenous fibrinolytic system. However, due to the small number of patients not all test parameters revealed significant changes. None of the PGE1 infusion regimens used (1.25 or 2.5 ng/kg/min i.a. or 5 or 10 ng/kg/min i.v. for 120 min in each case) led to any significant change in various parameters checked for ex-vivo platelet function. In agreement with these data the radioimmunological determination of PGE1 in venous plasma did not reveal any significant rise. On the other hand, the circulating metabolite of PGE1, 15-keto-13, 14-dihydro-PGE1, reached plasma levels which correlated well with expected theoretical values taking the infusion rate into consideration. A potential mechanism by which even low plasma concentrations of PGE1 might affect platelet function in vivo is discussed.

Alprostadil↗
PubMed1988

Effect of muscarinic receptor stimulation on release of cysteinyl-leukotrienes and thromboxane B2 from anaphylactic guinea-pig hearts.

The effects of muscarinic receptor stimulation by infusions of methacholine (6.25 x 10(-8) mol/min or 1.9 x 10(-7) mol/min) into isolated perfused, spontaneously beating sensitized guinea-pig hearts on the anaphylactic release of cysteinyl-leukotrienes (LT) and thromboxane (TX) B2 were investigated. Methacholine increased coronary flow and decreased heart rate under basal conditions. Furthermore, infusions of methacholine (1.9 x 10(-7) mol/min) significantly increased the anaphylactic release of TXB2 as well as of immunoreactive cysteinyl-LT, which were demonstrated by reversed phase high pressure liquid chromatography to consist of a mixture of LTC4, LTD4 and LTE4. Infusions of atropine (1.3 x 10(-7) mol/min) alone did not significantly affect coronary flow and heart rate prior to ovalbumin injection nor anaphylactic release of cysteinyl-LT. The anaphylactic release of TXB2 was, however, significantly decreased in the presence of atropine. Atropine (1.3 x 10(-7) mol/min) infused in addition to methacholine (1.9 x 10(-7) mol/min) abolished the effects of the muscarinic receptor agonist on spontaneous heart rate and significantly antagonized the increase in coronary flow prior to ovalbumin injection. Similarly, the simultaneous infusion of atropine abolished the effects of methacholine on the anaphylactic release of TXB2 and cysteinyl-LT. After antigen challenge hearts infused with methacholine, atropine or the combination of both drugs did not exhibit any differences with respect to anaphylactic changes of heart rate or the time course of anaphylactic coronary flow reduction. Thus, in the isolated perfused anaphylactic guinea-pig heart, muscarinic receptor stimulation significantly enhanced the release of the arachidonic acid-derived mediators TXB2 and cysteinyl-LT.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗