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Biomedical subjects

I Virgolini

Publications and source records attributed to I Virgolini.

At least 127 records · Page 7Linked to original sources
PubMed1989

[In vivo flow of autologous radioactively labeled low-density lipoproteins (LDL) in human blood vessels].

Following 123I-labelling and reinjection of autologous low-density lipoproteins (LDL) to patients with clinically manifest atherosclerosis and/or hyperlipoproteinaemia (HLP), an investigation was carried out of whole body kinetics and local kinetics over atherosclerotic lesions and areas of increased LDL entry identified by "hot spots" in the 123I-LDL scintigram. In patients with HLP the number and frequency of "hot spots" was higher than in normolipaemics. The time course of 123I-LDL influx into atherosclerotic lesion sites until scintigraphic visualization of "hot spots" exhibited three different types of LDL uptake among the patients. In the majority of patients LDL kinetics was characterized by entry into the vessels with the maximal radioactivity measured as early as within 60 minutes after reinjection. In some patients maximal radioactivity over lesion sites was discovered after 20 hours or even later. Morphological evaluation revealed that in comparison to control tissue, fatty streaks and lipid lesions show by far the highest 123I-LDL accumulation. Ex vivo measurement of the deposition of 125I-LDL in de- and re-endothelialized rabbit aortic segments exhibited a significantly (p less than 0.01 - p less than 0.001) higher 125I-LDL retention as compared with endothelialized segments (after i.v.-injection).

Adult↗
PubMed1989

[Do passive smokers have an increased risk of thrombosis?].

In contrast to the proven association between active smoking and vascular injury, as well as hemostatic imbalance, such a relation is not jet proven for passive smoking. Vascular damage induced by smoking, however, can be seen in the materno-fetal circulation of smoking mothers, being much more pronounced in the umbilical system than in fetal vessels. These lesions show fast recovery after birth. In non-smokers acute exposure to passive smoke induces a short-lasting activation of platelet function and the prostaglandin system, followed by a quick recovery. Chronic exposure of non-smokers to passive smoke, however, results in changes of these parameters comparable to those seen in smokers, characterized by an activation of platelet function and a decrease in platelet sensitivity to the antiaggregatory prostaglandin I2. These results suggest that in non-smokers with atherogenic risk factors passive smoking may contribute to the incidence of atherosclerosis, as well as acute complications (thrombosis).

Adult↗
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

Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF).

In order to evaluate the effect of PGI2 on left ventricular ejection fraction (LVEF) an intravenous infusion in 10 patients (3 males, 7 females; 36 to 63 years) with an impaired LVEF (34.7 +/- 14.8%) was performed. LVEF was determined by means of 99mTc-pertechnetate radionuclide ventriculography. An increase of LVEF to 36.2 +/- 13.5% during administration of PGI2 at a rate of 1 ng/kg/min for 15 min and to 43.8 +/- 15.8% during a rate of 5 ng/kg/min (p less than 0.01) for an additional 15 min was observed. Analyzing the data in more detail in 6 patients, an improvement in LVEF became obvious during the administration of 1 ng/kg/min (108, 109, 116, 118, 121, and 123% of pre-infusion value, respectively). In 5 out of these 6 patients a dose-increment to 5 ng/kg/min further increased LVEF (139, 179, 187, 148, and 128% of pre-infusion value, respectively). In contrast, in the other 4 patients no response of LVEF to PGI2 at a rate of 1 ng/kg/min could be observed. However, in 2 out of these 4 patients LVEF increased during the administration of 5 ng/kg/min (111 and 117% of pre-infusion value). Individual changes in hemodynamic parameters showed no correlation to the improvement seen in LVEF in response to PGI2. It is concluded that PGI2 may exert beneficial effects on LVEF, and might be used in certain clinical conditions, such as before heart transplantation, to achieve a temporary improvement in LVEF.

Adult↗
PubMed1989

Beneficial effect of long-term PGE1-treatment in left ventricular heart failure.

Five male patients aged 34-47 years with congestive heart failure showed an improvement of left ventricular ejection fraction (LVEF) at rather low PGE1-doses (10-30 ng/kg/min) without affecting blood pressure or heart rate. LVEF was estimated by means of radionuclide ventriculography (RNV) prior to and during i.v.-infusion of PGE1 at increasing dose rates (10-100 ng/kg/min). Therefore, we administered to these responders PGE1 at a rate of 20 ng/kg/min i.v. continuously on a long-term basis by means of a portable infusion pump. Until up to 4 months the remarkable benefit in LVEF induced by PGE1 was still present to a comparable extent in all the patients. No rebound desensitization phenomenon occurred either on platelet activity or on LVEF. PGE1, via a more practical route of application or by a stable analogue, may be a promising therapy at this stage of cardiomyopathy (CMP).

Adult↗
PubMed1989

Decrease of the prostaglandin I2 binding capacity in thyroids from patients with Graves' disease.

Properties of prostaglandin (PG) I2-binding sites in human thyroids from euthyroid and thyrotoxic patients were investigated. The specific binding of 3H-iloprost (ZK 36374, a chemically stable PGI2-analogue) to normal thyroids approached saturation at a concentration of more than 150 nmoles/L and could be displaced most effectively by unlabeled iloprost (concentration causing the half maximal inhibition, IC-50 = 5.9 +/- 2.9 mumoles/L) and PGI2 (IC-50 = 9.8 +/- 3.1 mumoles/L) and less effectively by unlabeled PGF2 alpha (IC-50 = 847.9 +/- 123.8 mumoles/L) at 4 degrees C. The Scatchard analysis clearly indicated heterogeneity revealing the presence of 0.65 +/- 0.18 pmoles/mg protein at the high-affinity binding sites (equilibrium dissociation constant, Kd = 18.2 +/- 9.1 nmoles/L) and 5.35 +/- 1.6 pmoles/mg protein at the low-affinity binding sites (Kd = 151.3 +/- 43.1 nmoles/L). In contrast, in diffuse colloid struma derived from patients with Graves' disease a single class of binding sites with an apparent binding capacity of 0.18 +/- 0.05 pmoles/mg protein (Kd = 70.4 +/- 27.3 nmoles/L) was indicated. However, in diffuse colloid struma derived from euthyroid patients no difference in the number of binding sites and binding affinity of 3H-iloprost was noted compared to normal thyroids. The data provide evidence for the presence of specific PGI2-binding sites in the human thyroid gland and demonstrate a significant decrease of the receptor density in patients with Graves' disease. It is suggested, that PGI2 has an important role in the regulation of human thyroid function.

Binding Sites↗
PubMed1989

Glucocorticoid-treatment does not influence the synthesis of thromboxane B2 and bicyclo-PGE2 in humans.

It has been reported that the anti-inflammatory action of glucocorticoids is due to the inhibition of phospholipases. Consequently, after high-dose steroid treatment in humans a decrease in cyclooxygenase products should be expected. In 15 patients (10 males, 5 females, 29-62 y) undergoing 6-methyl-prednisolone-treatment (40-80 mg daily) for various clinical reasons and in 5 healthy volunteers (4 male, 1 female, 28-37 y) receiving 500 mg 6-methyl-prednisolone daily for 3 days plasma- and serum-thromboxane B2 (TXB2), as well as bicyclo-prostaglandin E2 (bicyclo-PGE2) were monitored over 3 weeks. In the entire follow-up period, however, no significant change in either serum- or plasma-TXB2 or bicyclo-PGE2 could be measured in either, patients and volunteers, under glucocorticoid-treatment. These findings indicate that even high-dose glucocorticoid-treatment does not affect the serum- and plasma-metabolites of the eicosanoids examined. It is concluded that in humans a significant inhibition of phospholipases by glucocorticoids and subsequently reduced formation of cyclooxygenase products seems to be rather unlikely.

Adult↗
PubMed1989

Effects of taprostene, a chemically stable prostacyclin analogue, in patients with ischaemic peripheral vascular disease: a placebo controlled double-blind trial.

Thirty patients with ischaemic peripheral vascular disease and intermittent claudication were randomly allocated to receive either placebo or taprostene, a chemically stable prostacyclin analogue, intravenously at a rate of 25 ng/kg/min for 6 hours daily on 5 consecutive days. Taprostene produced a significant (p less than 0.05) increase in absolute walking time compared to placebo on one day after infusion and at 1, 4 and 8 weeks (14% vs 2.8%) later. Taprostene also produced a significant (p less than 0.05) increase in the pain-free walking time compared to placebo in the follow-up period (8 weeks after infusion: 23% vs 3.8%). During the infusion period systolic and diastolic blood pressure decreased (p less than 0.05) and heart rate was accelerated (p less than 0.05) in the taprostene treated group whereas no change was monitored in the placebo group. The ankle/brachial Doppler index was unaffected by taprostene. The platelet half-life was significantly (p less than 0.05) prolonged following taprostene-infusion (72.6 +/- 9.35 vs 77.9 +/- 7.44 hours). However, no change on platelet half-life was found in the placebo group (p less than 0.05). Various measures of platelet function parameters followed in vitro (ADP-induced aggregation, platelet sensitivity to PGI2, PGE1, PGD1 and taprostene, concentrations of platelet factor 4 and beta-thromboglobulin) showed no change with taprostene. Measures of circulating platelet aggregates and endothelial cells count showed no changes during the 2 months follow-up period too. It is assumed that taprostene may be of clinical benefit in patients with ischaemic peripheral vascular disease. However, future investigations have to be carried out to assess the optimal dose regime.

Alprostadil↗
PubMed1989

Human hepatocellular cancers show decreased prostaglandin E1 binding capacity.

Specific binding of 3H-PGE1 to plasma membranes prepared from normal human hepatic tissue in the presence of Mg2+ reached saturation at concentrations greater than 50 nM, and could be displaced in the rank-order PGE1 greater than PGE2 greater than PGI2 greater than PGD2 greater than PGF2 alpha at 4 degrees C. Plasma membranes prepared from normal human hepatic tissue showed a high-affinity 3H-PGE1-binding capacity of 51.3 +/- 19.2 fmol mg-1 plasma membrane protein with an equilibrium dissociation constant of 3.8 +/- 1.9 nM, and a low-affinity 3H-PGE1-binding capacity of 104.2 +/- 17.3 fmol mg-1 protein with an equilibrium dissociation constant of 13.9 +/- 2.7 nM. Plasma membranes prepared from hepatocellular cancer tissue revealed a single class of binding sites with an apparent binding capacity of 38.4 +/- 17.3 fmol mg-1 plasma membrane protein (P less than 0.05) and an equilibrium dissociation constant of 12.1 +/- 2.8 nM. Competition studies on plasma membranes prepared from hepatocellular cancer tissue indicated no significant difference in the affinity of various prostaglandins to the receptor proteins as compared to normal hepatic tissue. It is assumed that the decreased 3H-PGE1-binding capacity found in human hepatocellular cancer tissue may reflect an alteration of the receptor protein content of the hepatocytes during carcinogenesis.

Adult↗
PubMed1989

[Loss of high-affinity prostacyclin binding sites in patients with Basedow's disease].

Prostacyclin (PGI2) mediates like TSH its cellular effects through the interaction with specific binding sites associated with the adenylate cyclase-cAMP-system. Binding of PGI2 and the generation of cAMP induced by PGI2 was evaluated in thyroid tissue obtained intraoperatively from euthyroid and hyperthyroid patients with diffuse normofollicular colloid struma. Transformation of the binding data according to Scatchard revealed heterogeneity of the PGI2 binding sites in the tissue of euthyroid patients: the high-affinity binding sites were calculated to be 0.68 +/- 0.18 pmol/mg protein (Ka = 16.2 +/- 9.1 nM) and the low-affinity binding sites to be 5.4 +/- 1.6 pmol/mg protein (Ka = 151 +/- 43.1 nM). In contrast, in the hyperthyroid patients the low-affinity binding sites were not demonstrable and the high-affinity sites were significantly (p less than 0.001) reduced (0.17 +/- 0.05 pmol/mg protein, Ka = 83.5 +/- 19.6 nM). The competition of the agonist for the PGI2 sites in hyperthyroid patients was significantly (p less than 0.005) diminished (IC-50-values: 0.98 +/- 3.1 vs 46.9 +/- 12.1 microM). PGI2 stimulated cAMP-production in a dose-dependent manner. However, the basal value was significantly lower also in the hyperthyroid patients (p less than 0.001). The evidence of reduced PGI2 sites as well as reduced PGI2-induced cAMP production in the thyroid gland of patients with Graves' disease may indicate an important role for PGI2 to play in the modulation of thyroid cell function.

Adult↗
PubMed1989

Platelet aggregation and platelet sensitivity-behaviour during normal and abnormal glucose tolerance testing.

Platelet aggregation response to ADP and platelet sensitivity to the antiaggregatory prostaglandin I2 (PGI2) were measured in 15 patients and 8 healthy volunteers undergoing intravenous glucose tolerance testing (GTT). Eight patients (5 female, 3 male, 44-57a) showed pathological GTT, in 7 patients (6 female, 1 male, 39-55a) and the healthy volunteers (6 female, 2 male, 24-39a) a normal response was monitored. After GTT in patients with pathological GTT the slope of the ADP-induced aggregation curve was diminished showing high variations, whereas the height of the aggregation curve remained unaltered. The platelet sensitivity to PGI2 was significantly (p less than 0.05) decreased during the performance of GTT and returned to prevalues until the end of GTT. In the patients as well as in the healthy volunteers with normal GTT no change could be monitored during the test. However, healthy volunteers showed significant (p less than 0.05) lower prevalues. The findings indicate, that an abnormal glucose tolerance is associated with a decreased platelet sensitivity to PGI2.

Adult↗
PubMed1989

Pathomechanisms of atherosclerosis beneficially affected by prostaglandin E1 (PGE1)--an update.

The antiplatelet action of PGE1 was the basic concept for introducing this substance into clinical therapy of atherosclerosis. However, in the meanwhile a variety of other mechanisms have been discovered, which might be of importance, especially concerning the long-term benefit seen after treatment with PGE1, such as stabilization of endothelial lining, reflected by a decreased number of circulating endothelial cells and a decreased thrombogenicity (potentiated by endogenous EDRF-release), an inhibitory action on smooth muscle cells of the vessel wall such as decrease in mitotic and proliferative activity associated with a diminished extracellular matrix formation, an increase in fibrinolytic capacity, beneficial effects on white and red blood cells and some beneficial effects on the lipid metabolism by decreasing the arterial wall cholesterol content and upregulation of LDL-receptors as well as a moderate drop in serum cholesterol, seen in severe hypercholesterolemics only. It is assumed, that especially the vascular effects together with the hypolipidemic actions of PGE1 might be of major importance underlying the long-term benefit.

Alprostadil↗
PubMed1988

[Detection of a high-affinity prostaglandin I2 binding site in the human thyroid].

This study is concerned with the identification and the pharmacological properties of PGI2 receptor binding sites on human thyroid membrane fractions. Scatchard analysis is not linear, revealing a high- and a low-affinity receptor binding site. (3 H)Iloprost binding experiments were performed under various clinical conditions: in thyroid cancer the low-affinity binding sites disappear totally and the specific high-affinity binding sites are diminished according to the grade of differentiation of the cancer. An alteration in Bmax and Kd is also observed in cold nodules, in Hashimoto's and Riedl's thyroiditis and in hyperthyroidism, whereas hot nodules exhibit an increase in both the receptor subpopulations. The data provide evidence for specific PGI2 binding sites and support the suggestion of a direct regulatory key-role of PGI2 in thyroid intermediary metabolism.

Adult↗
PubMed1988

Evaluation of prostaglandin-receptors in human and rat liver: interspecies differences at the prostaglandin receptor-level.

The properties of PGE1-, PGE2- and iloprost (stable PGI2-analogue)-binding sites on normal human and rat liver surface cell membranes were investigated. The specific binding of [3H]PGE1 to human (rat) liver surface cell membranes could be displaced most effectively by unlabeled PGE1 (IC-50:2.5 +/- 1.7, (6.1 +/- 2.1) microM) and the specific binding of [3H]PGE2 by unlabeled PGE2 (IC-50: 1.9 +/- 0.9 (2.0 +/- 0.8) microM. The Scatchard analysis on [3H]PGE1- as well as on [3H]iloprost-binding was curvilinear whereas it was clearly linear on [3H]PGE2-binding in both the species. The high-affinity [3H]PGE1-sites showed a Bmax of 36.3 +/- 5.2 (21.3 +/- 4.3) fmol/mg protein and a Kd of 2.1 +/- 1.8 (1.9 +/- 0.7) nM, the low-affinity [3H]PGE1-sites a Bmax of 93.4 +/- 18.2 (86.1 +/- 13.2) fmol/mg protein and a Kd of 10.5 +/- 2.9 (15.1 +/- 3.2) nM. The high-affinity [3H]iloprost-sites exhibited a Bmax of 71.4 +/- 13.9 (35.9 +/- 8.2) fmol/mg protein and a Kd of 4.1 +/- 1.2 (1.7 +/- 1.8) nM, the low-affinity [3H]iloprost-sites a Bmax of 217.3 +/- 42.1 (142.9 +/- 17.8) fmol/mg protein and a Kd of 16.3 +/- 4.9 (9.2 +/- 7.2) nM. The [3H]PGE2-sites showed a Bmax of 135.4 +/- 51.9 (38.8 +/- 7.4) fmol/mg protein and a Kd of 16.2 +/- 3.2 (2.5 +/- 1.2) nM. It is assumed that prostaglandins of the E-series are promising substances in the regulation of human and rat liver function since liver cells are able to bind reasonable amounts of these substances in a high affinity manner. However, interspecies differences in the affinity of the prostaglandins to their receptor-sites make it strange to assume that the same biological findings claimed several times for the rat liver are relevant for human too.

Animals↗
PubMed1988

High-performance-liquid-chromatographic analysis of radiolabelled prostaglandins and fatty acids with the radial compression column.

The method described is a rapid and reproducible separation of different prostanoids. With the use of a reversed phase 5 micron-radial compression column instead of a steel column-HPLC analysis is improved within a shorter time. In order to separate also the non-polar substances like arachidonic acid (AA) and hydroxy fatty acids in an appropriate time, a gradient-elution is used. The radioactivity is counted immediately after the column within a radioactivity monitor. With this system it is possible to examine the AA-metabolites enzymatically formed in cells or tissue from exogenous AA.

Aged↗