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Biomedical subjects

A G Herman

Publications and source records attributed to A G Herman.

At least 181 records · Page 10Linked to original sources
PubMed1986

Prostacyclin and thromboxane in benign and malignant breast tumours.

6-keto-PGF1 alpha and thromboxane B2 were determined by radioimmunoassay in 37 extracts of breast carcinomata, 8 fibroadenomata, 12 sclerocystic-disease specimens and 51 normal breast tissues. More prostanoids were extracted from carcinomata than from normal specimens, fibroadenomata or sclerocystic-disease tissues (P less than 0.05). The 6-keto-PGF1 alpha/TXB2 ratio was higher in carcinomata than in normal tissues and fibroadenomata (P less than 0.05) but was not significantly different from the ratio in sclerocystic disease. The prostaglandin levels and the 6-keto-PGF1 alpha/TXB2 ratios from carcinomata did not correlate significantly with age, tumour size, differentiation, lymph node status, nuclear-cytoplasmic ratio, host cell reaction, mast cells, necrosis, elastosis, fibrosis or blood vessel density. Lower nuclear density was associated with lower 6-keto-PGF1 alpha/TXB2 ratios (P = 0.01) whereas the latter value was higher when infiltration was lower (P = 0.03). There was a positive correlation between mitotic index and the 6-keto-PGF1 alpha/TXB2 ratio (P = 0.04). Cumulation of variables revealed lower prostanoid ratios in tumours greater than 2 cm without lymph node metastasis then tumours less than 2 cm with lymph node metastasis (P = 0.04). A first follow-up (14 months) showed a higher 6-keto-PGF1 alpha/TXB2 ratio in patients who developed metastasis (P = 0.04). Our study does not confirm the hypothesis that high prostacyclin levels are a good prognostic index in breast cancer.

Adolescent↗
PubMed1986

Study of prejunctional beta-adrenoceptors in kidneys of normotensive and hypertensive rats using the new beta-adrenoceptor blocking drug tertatolol.

The prejunctional beta-adrenoceptors present in the isolated perfused kidney of normotensive rats (NR) and spontaneously hypertensive rats (SHR) were compared and the effects of tertatolol on these receptors were investigated. Kidneys of NR (Wistar + Wistar-Kyoto [WKY]) and SHR, were continuously perfused with Tyrode solution at constant flow and the changes in perfusion pressure were monitored. The constrictor responses to norepinephrine (2-8 X 10(-10) moles) were slightly but significantly decreased by isoproterenol (2 X 10(-7) M) to a similar degree in NR and SHR. Tertatolol (3 X 10(-7) M) did not alter the constriction caused by norepinephrine, but abolished the dilator response to isoproterenol. Electrical stimulation of renal nerves (8 Hz) evoked constrictions in both NR and SHR; these constrictor responses were augmented in the presence of isoproterenol (2 X 10(-7) M) to a similar extent in NR and SHR. In kidneys of NR and SHR, previously incubated with 3H norepinephrine, renal nerve electrical stimulation (6 Hz) evoked an overflow of the 3H transmitter. This overflow was enhanced by isoproterenol (2 X 10(-6) M) to a similar degree in NR and SHR. Both the augmented constrictor response and the augmented overflow of 3H norepinephrine caused by electrical stimulation in the presence of isoproterenol, were inhibited by tertatolol (3 X 10(-7) M). Our results show that the beta-receptor agonist isoproterenol evokes comparable effects at prejunctional beta-adrenoceptors in kidneys of NR and SHR; they also show that tertatolol is an inhibitor of pre- and postjunctional beta-adrenoceptors in the renal circulation of the rat.

Adrenergic beta-Antagonists↗
PubMed1986

Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits.

We studied the effects of hypercholesterolemia on vascular responsiveness in different arteries isolated from rabbits: control groups of rabbits and groups receiving the atherogenic diet consisted of eight animals each. In the arteries, 16 weeks of cholesterol-rich (0.3%) diet evoked intimal lesions which were more pronounced than those noted after 8 weeks of hypercholesterolemia; the aortic arch was affected significantly more by the lesions than the abdominal aorta and the pulmonary artery. Segments of the arteries were mounted in organ chambers for isometric tension recording or for measurement of the endothelium-derived relaxant factor. Contractions caused by acetylcholine and prostaglandin F2 alpha were not altered by the hypercholesterolemia; those evoked by serotonin were moderately augmented only in the aortic arch of hypercholesterolemic rabbits. As the degree of intimal lesion formation increased, the contractions to norepinephrine and clonidine were progressively inhibited. The endothelium-independent relaxations to nitroglycerin were inhibited in only the most severely affected arteries; the endothelium-dependent relaxations to acetylcholine and adenosine triphosphate were progressively inhibited as the degree of fatty streak formation augmented. Thus, in the aortic arch, the relaxations to 3 X 10(-6) M acetylcholine, expressed as percent of the initial contraction, decreased from 86.7 +/- 3.3% in control tissues to 16.3 +/- 8.6% in the 16-week hypercholesterolemic vessels; in the abdominal aortas these relaxations averaged 93.5 +/- 2.2% in control vessels and 72.0 +/- 6.9% in the hypercholesterolemic tissues. The acetylcholine-induced release of endothelium-derived relaxant factor from the abdominal aorta was not significantly affected by the hypercholesterolemia. We conclude from these studies that in arteries obtained from hypercholesterolemic rabbits: the contractions caused by serotonergic mechanisms tend to be augmented, while those to alpha-adrenergic activation are decreased, the endothelium-independent relaxations are modified only in the more severely affected arteries, and the endothelium-dependent relaxations are progressively inhibited as the degree of fatty streak formation augments, probably because a step subsequent to the release of endothelium-derived relaxant factor is altered.

Acetylcholine↗
PubMed1986

Effect of hypercholesterolemia on vascular reactivity in the rabbit. II. Influence of treatment with dipyridamole on endothelium-dependent and endothelium-independent responses in isolated aortas of control and hypercholesterolemic rabbits.

The effects of cholesterol-feeding in the presence of dipyridamole (0.60 g daily) on contractile responses and on endothelium-dependent and endothelium-independent relaxations in isolated rabbit aortas are described. The investigations were performed simultaneously with those described in Part I (Circ Res 1986; 58:552-564), where the effects of cholesterol feeding on vascular reactivity in rabbit arteries (n = 8 in each group) selected at random from the same group of animals was studied. In the hypercholesterolemic rabbits treated with dipyridamole for 8 or 16 weeks, both the increases in plasma cholesterol and the formation of fatty streaks were significantly less pronounced than in the hypercholesterolemic rabbits not receiving the drug. Segments of the isolated arteries were mounted in organ chambers for isometric tension recording. The contractions caused by acetylcholine, prostaglandin F2 alpha, norepinephrine, clonidine, and serotonin and the endothelium-independent relaxations to nitroglycerin were not significantly altered by the hypercholesterolemia in rabbits treated with dipyridamole, even after 16 weeks of treatment. Thus, the decreased responses to norepinephrine, clonidine, and nitroglycerin and the augmented responses to serotonin noted in aortas of hypercholesterolemic rabbits in Part I were absent in the dipyridamole-treated hypercholesterolemic animals. The endothelium-dependent relaxations to ATP and acetylcholine were not affected after 8 weeks of hypercholesterolemia in presence of dipyridamole, while after 16 weeks the relaxations to ATP and acetylcholine were attenuated only in the more severely affected arteries. The effects of hypercholesterolemia + dipyridamole on endothelium-dependent relaxations were significantly less pronounced than those induced by hypercholesterolemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of the amino-oxazoline derivative S-3341 on pre- and postjunctional alpha-adrenoceptors in isolated blood vessels.

In segments of isolated dog saphenous veins, S-3341 (10(-8) to 10(-4) M) induced concentration-dependent contractions which, like those to clonidine, were progressively inhibited by increasing concentrations of yohimbine (10(-8) to 10(-6) M) but not by prazosin (10(-8) to 10(-6) M). In strips of the rabbit main pulmonary artery, previously labelled with [3H]noradrenaline and mounted for superfusion, S-3341 and clonidine both decreased the overflow of [3H] caused by electrical stimulation; these effects of S-3341 and clonidine were inhibited by 10(-6) M of yohimbine but not by 10(-6) M of prazosin. Our results illustrate that both S-3341 and clonidine cause contraction by activation of postjunctional alpha 2-adrenoceptors and decrease noradrenaline-release by stimulating prejunctional alpha 2-adrenoceptors. At the postjunctional alpha 2-adrenoceptors clonidine is 27 times more potent than S-3341, while at the prejunctional alpha 2-adrenoceptors, clonidine is only 15 times more potent than S-3341.

Animals↗
PubMed1986

6-keto-PGF1 alpha levels and prostacyclin therapy in 2 adult patients with hemolytic-uremic syndrome.

Evidence supports the hypothesis that plasma prostacyclin activity is deficient in hemolytic-uremic syndrome (HUS). We studied 2 adult patients with HUS. Plasma levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, were measured by radioimmunoassay. Both patients were found to have elevated 6-keto-PGF1 alpha levels. These findings are in contradiction with the prostacyclin deficiency hypothesis and with earlier reports of low or undetectable plasma levels of this metabolite. The patients were treated with IV prostacyclin after a single plasma exchange. The first patient, admitted with advanced renal failure, obtained a rapid remission but renal function did not recover; the second patient, admitted with a less pronounced degree of renal failure, reacted slowly to therapy but renal function partially recovered. We believe that, if any benefit is to be expected from prostacyclin therapy in HUS, it should be started early in the course of the disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Vernolepin: an antiplatelet compound of natural origin.

Vernolepin, a natural compound isolated from Vernonia amygdalina Del., shows platelet anti-aggregating properties. In this paper some of its pharmacological activities towards rabbit platelets are studied. Vernolepin has a "stabilizing" effect during freeze-thawing of platelets, it inhibits arachidonic acid, ADP and collagen-induced platelet aggregation and interferes with ATP-release. Electromicroscopy shows a protection of platelets by the drug against adhesion and a desaggregating effect. All these activities are time dependent; a steep dose response relationship is seen. A concentration of 1 X 10(-5) g/ml seems to be optimal.

Adenosine Diphosphate↗
PubMed1985

No evidence for a physiological role of 5-hydroxykynuramine in chicken hemostasis.

Pharmacological effects of 5-hydroxykynuramine (5-HK) were investigated in chicken whole blood. It was shown that 5-HK had a time-depending inhibiting activity on platelet aggregation induced by 5-hydroxytryptamine (5-HT). Experiments were carried out in order to determine whether the inhibitory effect of chicken aorta upon 5-HT-induced aggregation of chicken whole blood could be explained by the formation of 5-HK, a metabolite of 5-HT. Using high performance liquid chromatography (HPLC) in combination with sensitive electrochemical detection, the presence of 5-HK could not be confirmed in chicken blood or aortic tissue, despite the fact that 5-HT levels of chicken blood (6.78 +/- 0.54 micrograms/ml) and aorta (0.69 +/- 0.11 micrograms/g of tissue wet weight) could be determined. These results do not point to a physiological role of 5-HK in chicken whole blood aggregation.

Animals↗
PubMed1985

Isolation and identification of two isomeric trihydroxy octadecenoic acids with prostaglandin E-like activity from onion bulbs (Allium cepa).

Two fractions with prostaglandin E-like activity were isolated from onion (Allium cepa) by using XAD-2 adsorption, silicic acid column chromatography and thin layer chromatography. The fractions were analyzed by gas chromatography/mass spectrometry and were characterized as isomeric mixtures of 9,10,13-trihydroxy-11-octadecenoic and 9,12,13-trihydroxy-10-octadecenoic acid, which are lipoxygenase metabolites of linoleic acid. Bio-assay, for which cascade superfusion was used and the rabbit coeliac and mesenteric arteries and the rat fundus strip were employed as assay organs, was utilized to monitor the bio-active profile throughout the isolation procedures. The activity of 1 microgram of the pharmacologically active fractions T1 and T2 was found to be equivalent to that of respectively 1.33 and 0.63 ng of prostaglandin E2.

Chromatography, Gel↗
PubMed1985

Prostaglandin F2 alpha in benign and malignant breast tumours.

Prostaglandin F2 alpha (PGF2 alpha) was determined by radioimmunoassay in 57 breast carcinomata, 16 fibroadenomata, and 33 sclero-cystic-disease (SCD) specimens. In 41 cases of carcinoma and 10 cases of fibroadenoma, histologically non-malignant tissue was also obtained from the same breast. PGF2 alpha levels were significantly elevated in breast cancer when compared with the normal tissues and benign diseases (P less than 0.005 for each group). High PGF2 alpha levels were positively correlated with differentiation, positive oestrogen and progestagen receptor status, and low mitotic index. Tumours with good prognosis (less than 20 mm, negative lymph nodes, some degree of differentiation) showed significantly higher PGF2 alpha levels than tumours with a bad prognosis (greater than 20 mm, positive nodes and undifferentiated). A tendency for elevated PGF2 alpha levels was observed with negative lymphatic permeation, postmenopausal status, low grade of nuclear and cellular polymorphism and high degree of elastosis and fibrosis. No correlation was observed between PGF2 alpha levels and host-cell reaction. Plasma levels of 15-keto-13, 14-dihydro-PGF2 alpha were not elevated in cancer patients when compared with the SCD-group. The present study demonstrates that PGF2 alpha levels are high in tumours with good prognosis. However, since other authors have suggested that a high PGE2 production is a bad prognostic index, it is possible that conversion of PGE2 to PGF2 alpha by 9-keto-reductase explains this relationship. Nevertheless, the presented results question the unrestricted use of prostaglandin-synthesis-inhibitors in the treatment of breast cancer.

Adenofibroma↗
PubMed1985

Modification of endotoxin-induced haemodynamic and haematological changes in the rabbit by methylprednisolone, F(ab')2 fragments and rosmarinic acid.

The effects of methylprednisolone, F(ab')2 fragments of human gamma globulins and rosmarinic acid, an inhibitor of complement activation, were tested on endotoxin-induced haemodynamic and haematological changes in the rabbit. Their effects were compared with complement depletion by cobra venom factor (CVF) pretreatment. The results provide further evidence for the role of complement activation and the concomitant triggering of the arachidonic acid cascade in the early phase of shock. The formation of vasoactive prostanoids (prostacyclin and thromboxane A2), the arterial hypotension and the thrombocytopenia were largely dependent on the presence of the intact complement system. F(ab')2 fragments (150 mg kg-1, i.v.) diminished the second fall in blood pressure to some extent but failed to alter any of the other endotoxin-induced changes. Methylprednisolone (40 mg kg-1, i.v.) given 10 min before endotoxin significantly reduced the activation of complement, the second rise of prostacyclin and the secondary hypotension, but was without effect on the early thromboxane peak of the haematological features of endotoxin shock. Rosmarinic acid (20 mg kg-1, i.v.) may be of potential interest for treatment of septic shock, since the drug suppressed the endotoxin-induced activation of complement, the formation of prostacyclin, both hypotensive phases, the thrombocytopenia and the concomitant release of thromboxane A2. The role of leukocytes and their arachidonic acid metabolites in plasma exudation deserves further investigation, because leukopenia and pulmonary oedema were not complement-dependent and were not affected by any of the treatments. Our results indicate that drugs, interfering with complement activation and/or prostaglandin biosynthesis, may be beneficial in endotoxin shock, provided that they are administered at an early stage.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Formation of prostanoids during intravascular complement activation in the rabbit.

Plasma concentrations of 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (TXB2) were measured by radioimmunoassay in arterial blood before and after injections of the complement activator, cobra venom factor (CVF). During the control period, the concentration of 6-oxo-PGF1 alpha, which gives the sum of prostacyclin plus 6-oxo-PGF1 alpha, and TXB2 were, respectively, less than 20 pg ml-1 and 70 +/- 15 pg ml-1. Intravenous injections of CVF induced dose-dependent, reversible elevations in the plasma levels of both prostanoids. The time courses for the increases of 6-oxo-PGF1 alpha and TXB2 paralleled the arterial hypotension and thrombocytopenia, suggesting the existence of a causal relationship between these parameters. The results further support our hypothesis that complement-dependent formation of arachidonic acid metabolites contributes to some of the haemodynamic and haematological changes occurring during endotoxin shock.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Effects of tertatolol on post- and prejunctional beta adrenoceptors.

The effects of tertatolol, a new and powerful beta adrenoceptor blocking drug, on post- and prejunctional beta receptors were investigated; canine vascular tissues (saphenous veins, coronary arteries and splenic arteries) and guinea-pig trachea and atria were used. At concentrations below 10(-5) M, tertatolol did not alter basal tension or contractile responses to electrical stimulation, norepinephrine, K+ or prostaglandin F2 alpha; at doses at or above 10(-5) M the drug-evoked contractions which were reduced by phentolamine and were absent in denervated veins. Tertatolol at 10(-5) M and 3 X 10(-5) M augmented the basal efflux of [3H] norepinephrine in saphenous veins labeled with the 3H-transmitter. In veins, 10(-5) M of tertatolol depressed the contractions caused by electrical stimulation without affecting those to exogenous norepinephrine; this concentration of the drug also inhibited the stimulation-induced overflow of [3H]norepinephrine. The major part of the present study was designed to test the beta receptor blocking properties of tertatolol and to compare its effects with those of propranolol. Tertatolol inhibited, in a concentration-dependent manner, the relaxations caused by isoproterenol in saphenous veins, splenic arteries and coronary arteries and the relaxations evoked by norepinephrine and epinephrine in coronary arteries; the potency of tertatolol was higher than that of propranolol. In trachea and right atria of the guinea-pig, tertatolol inhibited, in a concentration-dependent manner, the dose-response curves to isoproterenol; the relative potency of tertatolol was higher than that of propranolol. In dog saphenous veins, previously incubated with [3H]norepinephrine, tertatolol (10(-7)M) blocked the increased stimulation-evoked overflow of the 3H-transmitter induced by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

Stimulation of prostacyclin production by vitamin C in ram seminal vesicle microsomes: possible mode of action.

The enhancing effect of vitamin C on the conversion of arachidonic acid, endoperoxide G2 and endoperoxide H2 to 6-keto-PGF 1 alpha, the stable metabolite of prostacyclin, by ram seminal vesicle microsomes was further investigated. From the incubations of these substrates with 1-tryptophan, catalase, superoxide dismutase and 15-HPETE it became clear that vitamin C apparently acts mainly through neutralization of the oxidative species formed during the reduction of endoperoxide G2 to endoperoxide H2. Although it has also a more direct stimulating activity on the prostacyclin synthase, a possible interference with hydroperoxy derivatives of arachidonic acid cannot be completely ruled out.

Animals↗