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S Kapiotis

Publications and source records attributed to S Kapiotis.

At least 91 records · Page 5Linked to original sources
PubMed1997

Oxidized low-density-lipoprotein triggers programmed death of endothelial cells.

Incubation of bovine aortic as well as human umbilical vein endothelial cells with either oxidized or native low-density-lipoprotein in the presence of trace amounts of copper induced morphological changes of the cells and chromatin fragmentation characteristic for programmed cell death. Shrinkage of cells was evident after 6 to 8 hours of incubation and clearly preceded release of lactate dehydrogenase as a marker of cell permeability. Condensation of nuclear chromatin and internucleosomal cleavage was demonstrated by Hoechst staining and gel electrophoresis, respectively. Thus, by inducing active death of endothelial cells oxidized low-density-lipoprotein might negatively influence tissue homeostasis of the endothelium and thereby promote the development of atherosclerotic plaques.

Animals↗
PubMed1997

No evidence of activated blood coagulation in Crohn's disease.

BACKGROUND: Thromboembolism seems to be a significant and serious complication in Crohn's disease (CD), and multifocal microvascular infarction of the intestinal mucosa may be an important effector mechanism in the pathogenesis of CD. Therefore, it has been hypothesized that an increased activation of the blood coagulation system may favour thromboembolic complications. OBJECTIVES: To assess the activity of blood coagulation as a potential index of thromboembolic risk in CD using thrombin-antithrombin III complex (TAT). DESIGN: Prospective evaluation of TAT. SETTING: Out-patients at the gastroenterological department of a university hospital. PATIENTS: Eighty patients with CD, 47 with inactive (Crohn's disease activity index (CDAI) < 150) and 33 with active disease, and 80 healthy controls were investigated in this study. METHODS: TAT and fibrinogen were used as parameters of blood coagulation. C-reactive protein and orosomucoid were used as serum inflammatory parameters. RESULTS: Fibrinogen was significantly higher in patients with active CD (median 535 mg/dl; interquartile range 402-620 mg/dl) than in patients with inactive CD (357 mg/dl; 300-467 mg/dl) or controls (268 mg/dl; 231-299 mg/dl). Fibrinogen correlated with CDAI, C-reactive protein and orosomucoid. TAT did not show any difference between patients with active CD (3.2 ng/ml; 2.5-4.6 ng/ml), inactive CD (3.0 ng/ml; 2.4-3.9 ng/ml) and controls (3.1 ng/ml; 2.3-3.6 ng/ml). Correspondingly, TAT correlated neither with serum inflammatory parameters and CDAI nor with fibrinogen. CONCLUSION: We could not find evidence of activation of the blood coagulation system as determined by TAT plasma levels in CD, not even in patients with active disease. TAT is not, therefore, a potential index of thromboembolic risk in CD and of microvascular infarction as an effector mechanism in the pathogenesis of CD.

Adult↗
PubMed1997

Paracetamol catalyzes myeloperoxidase-initiated lipid oxidation in LDL.

The oxidative modification of LDL may play a significant role in atherogenesis. Myeloperoxidase (MPO) expressed in human atherosclerotic plaques has been suggested to be operative in vivo, making LDL atherogenic. Tyrosyl radicals generated by MPO have been shown to act as physiological pro-oxidants of lipid peroxidation in LDL. Assuming that a variety of phenolic compounds are able to form phenoxyl radicals when exposed to peroxidases, we tested the ability of paracetamol, a known analgesic drug with a tyrosine-like monophenolic structure, to act as a pro-oxidant of lipid peroxidation in LDL. Spectroscopic analyses indicated that paracetamol, similar to tyrosine, could undergo peroxidase-induced phenoxyl radical formation, which was inhibited by the radical scavenger ascorbic acid as well as by heme poisons and catalase. Measurement of conjugated dienes and lipid hydroperoxides in LDL preparations exposed to MPO/H2O2 in the absence or presence of paracetamol revealed that the drug could act as a catalyst of lipid oxidation in LDL. Similar results were found when LDL oxidation was performed with activated human neutrophils, which use MPO to promote lipid peroxidation. In conclusion, the results suggest that paracetamol could act, via a phenoxyl radical, as a catalyst of LDL oxidative modification by MPO.

Acetaminophen↗
PubMed1997

Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis, and endothelial cell integrity in healthy men.

On the basis of an array of preclinical experimental results, it has been widely assumed that endothelin-1 (ET-1) may affect blood coagulation, fibrinolysis, and endothelial cell function, thereby playing a pathophysiological role in various cardiovascular diseases in humans. However, confirmation of this assumption is still lacking. ET-1 or placebo was administered intravenously to 12 healthy volunteers in a prospective, randomized, double-blind, crossover trial. Pathophysiologically relevant concentrations of ET-1 (an approximate threefold increase of normal blood levels) causing hemodynamic effects were reached by continuous intravenous infusion for 6 hours. Components of the coagulation (thrombin-antithrombin complexes, prothrombin fragment F1 + 2, activated factor VII, and factor VII antigen) and fibrinolytic (fibrin split product D-dimer, plasmin-plasmin inhibitor complex, tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1) systems and markers of endothelial cell perturbation/dysfunction (von Willebrand factor and thrombomodulin) were measured before the start of infusion and after 2, 6, 12, and 24 hours. Comparing changes in the plasma concentrations of these parameters during and after infusion of ET-1 and placebo, we found no specific effects of ET-1. In contrast to previous reports from preclinical experiments, ET-1 does not appear to affect coagulation or fibrinolysis, nor does this peptide induce relevant endothelial cell perturbations in humans.

Adult↗
PubMed1997

Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL.

There is now growing evidence that the oxidative modification of LDL plays a potential role in atherosclerosis. In this study, genistein, a compound derived from a soy diet with a flavonoid chemical structure (4',5,7-trihydroxyisoflavone), which was found to inhibit angiogenesis, has been evaluated for its ability to act as an LDL antioxidant and a vascular cell protective agent against oxidized LDL. The results showed that genistein was able to inhibit the oxidation of LDL in the presence of copper ions or superoxide/nitric oxide radicals as measured by thiobarbituric acid-reactive substance formation, alteration in electrophoretic mobility, and lipid hydroperoxides. Bovine aortic endothelial cell- and human endothelial cell-mediated LDL oxidation was also inhibited in the presence of genistein. The 7-O-glucoside of genistein, genistin, was much less effective in inhibiting LDL oxidation in the cell-free and cell-mediated lipoprotein-oxidating systems. Incubating human endothelial cells in the absence or presence of genistein and challenging the cells with already oxidized lipoprotein revealed that in addition to its antioxidative potential during LDL oxidating processes, genistein effectively protected the vascular cells from damage by oxidized lipoproteins. The tyrosine kinase inhibitor genistein was found to block upregulation of two tyrosine-phosphorylated proteins of 132 and 69 kDa in endothelial cells induced by oxidized LDL. Parallel experiments with the inactive analogue daidzein, however, showed that the cytoprotective effect of the isoflavones seems not to be dependent on tyrosine phosphorylation. Our findings will support the suggested and documented beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Animals↗
PubMed1997

Hemodynamic effects of parathyroid hormone-related peptide-(1-34) in humans.

It has been suggested that PTH-related peptide-(1-34) (PTHrP) is a regulator or modulator of regional or systemic cardiovascular function with varying vasodilating actions in different species. We have studied the cardiovascular pharmacodynamic profile of PTHrP in healthy humans. In a double blind, placebo-controlled, cross-over study design, eight healthy subjects were assigned to stepwise increased i.v. doses of PTHrP. In addition, a dose-response curve to PTHrP was constructed in a dorsal hand vein in eight subjects. PTHrP dose-dependently increased pulse rate and renal plasma flow by more than 50% (P < 0.0001 for both parameters, by ANOVA), but only a small venodilating response was seen in hand vein experiments, and no effect was noted on mean arterial blood pressure or cardiac inotropic performance. Although it is unlikely that PTHrP regulates systemic hemodynamics, its chronotropic effect and its potent action on renal plasma flow may represent the primary cardiovascular physiological targets of action.

Adult↗
PubMed1997

Thrombin augments vascular cell-dependent migration of human mast cells: role of MGF.

Recent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine- (HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 +/- 344 cells [100 +/- 11.4%] vs. MGF, 100 ng/ml: 8806 +/- 1019 [291 +/- 34%] vs. HAUEC: 9703 +/- 1506 [320.8 +/- 49.8%] vs. HUTMEC: 8950 +/- 1857 [295.9 +/- 61.4%] vs. HSMEC: 9965 +/- 2018 [329.4 +/- 66.7%] vs. HUVEC: 9487 +/- 1402 [313.6 +/- 46.4%], p < 0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

Blotting, Northern↗
PubMed1997

Partial blockade of nitric oxide synthase blunts the exercise-induced increase of von Willebrand factor antigen and of factor VIII in man.

BACKGROUND: Until now the effects of beta-adrenergic agonists have largely been ascribed to their ability to induce intracellular formation of cyclic adenosine monophosphate. Recently evidence has been accumulating that at least some beta1 and beta2-adrenoceptor effects may be mediated by nitric oxide (NO). Based on these studies, we hypothesized that the beta-adrenoceptor mediated increase of von Willebrand factor and factor VIII-activity (FVIII:C) in plasma during exercise, is caused by an NO-dependent mechanism. METHODS: Thirteen young healthy subjects finished an exhaustive bicycle exercise protocol while they were infused placebo or the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) on two separate days in a randomized, double blind cross-over design. FINDINGS: During exercise systemic haemodynamic changes were parallel in both treatment periods, but L-NMMA caused a partial inhibition of NO-synthase as evidenced by a 30% decrease in exhaled NO. The workload capacities were not different during L-NMMA or placebo infusion. However, under placebo treatment exercise increased vWF-Ag by a maximum of 61% (CI: 43-84; p = 0.002) and FVIII:C by 44% (CI: 31-59; p = 0.001), which was significantly attenuated when subjects were treated with L-NMMA (p <0.05): under L-NMMA treatment vWF-Ag increased by only 25% (CI: 5-51; p = 0.001) and FVIII:C by 12% (CI: 6-39; p = 0.001). INTERPRETATION: Partial blockade of NO-synthase with L-NMMA blunts the exercise-induced increase in vWF-Ag and FVIII:C. Our trial points to a role of endogenous NO-generation in the beta2-adrenergic increase in vWF/FVIII. Thus, we propose that physiologic processes which are induced by systemic beta2-adrenoceptor stimulation may at least partly be mediated by NO.

Adult↗
PubMed1996

Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells.

Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug.

Base Sequence↗
PubMed1996

Effects of desmopressin on circulating P-selectin.

Von Willebrand factor (VWF) and P-selectin share an identical intracellular storage compartment and transport to the cell surface. We induced degranulation of the Weibel-Palade bodies and measured circulating (c)P-selectin in plasma to test whether soluble P-selectin is present in the Weibel-Palade bodies, or if P-selectin bound to the cell membrane of endothelial cells (EC) is rapidly proteolytically cleaved in vivo. A dose of 0.3 microgram/kg of desmopressin (DDAVP) or placebo was infused over 30 min to eight healthy men in a double-blind cross-over study. Plasma levels of cP- selectin and VWF-Ag were followed for 24 h. Despite a twofold increase in VWF-Ag levels immediately after a 2 h after infusion of DDAVP, no significant change in plasma concentrations of cP-selectin were observed. In summary, degranulation of the Weibel-Palade bodies is an unlikely source of cP-selectin. Thus cP-selectin in healthy subjects is conceivably attributable to other mechanisms, such as minor degrees of platelet activation or transcription induction of an alternatively spliced P-selectin.

Adult↗
PubMed1996

Improved characteristics of aPC-resistance assay: Coatest aPC resistance by predilution of samples with factor V deficient plasma.

Screening for a resistance against activated protein C (aPCR), which is in most cases caused by FV:Q506 mutation, is performed by functional tests measuring the effect of aPC on activated partial thromboplastin time (aPTT). Because of an insufficient discrimination between FV:Q506 mutation negative and positive individuals with the first generation of the functional test Coatest aPC Resistance (Chromogenix AB, Mölndal, Sweden), the definition of an arbitrary cut-off level was only possible using the results of DNA analysis. The use of an arbitrary cut-off level still resulted in unsatisfactory low sensitivity and specificity for the functional test. Thus, time- and cost-consuming DNA analyses had to be performed frequently to establish the diagnosis. The objective of this study was to evaluate an improved version of this assay that uses predilution of samples with factor V deficient plasma containing a heparin neutralizer. Using the data from 32 FV:Q506 mutation positive and 55 mutation negative individuals, the authors calculated a cut-off value resulting in an enhanced sensitivity (0.91 versus 1.0) and specificity (0.77 versus 1.0) compared to the old one. Imprecision was lowered from 5.36% (first generation) to 2.43%, in particular in samples with longer clotting times. In patients with prolonged aPTT, either caused by therapy with oral anticoagulants or heparin, correct results were obtained with the second generation assay, in contrast to the first generation assay. With this second generation assay the number of DNA analyses can be substantially reduced.

Adult↗
PubMed1996

Immunoglobulin E response to human proteins in atopic patients.

The demonstration that human IgE recognizes both exogenous allergens and structurally related human proteins has led to the hypothesis that IgE autoreactivity may be a pathogenic factor in atopic diseases. To determine the frequency of occurrence as well as the disease specificity of this phenomenon, we tested sera from patients with atopic diseases and, for control purposes, from persons with immunologically mediated disorders for serum IgE reactivity with nitrocellulose-blotted human proteins. We found that 12 of 20 sera from atopic patients with pronounced skin lesions contained Western blot-detectable IgE antibodies. Patients suffering predominantly from allergic rhinoconjunctivitis as well as control individuals failed to display serum IgE autoreactivity, but occasionally exhibited elevated serum IgE levels. The molecular weights of the IgE-defined autoantigens ranged predominantly from 10 to 100 kDa. Whereas some of these were expressed in only certain cell types, others were detected in histogenetically different cells. Our results suggest that IgE autoimmunity occurs frequently in atopic dermatitis patients and may be of pathogenic relevance for the chronicity of skin manifestations typical of this disease.

Antibody Specificity↗
PubMed1996

Course of pseudocholinesterase isozymes during an acute phase in Crohn's disease.

We have previously shown that the percentage distribution of the pseudocholinesterase isozymes (C1, C2, C3 and C4) is significantly altered in patients with active Crohn's disease (CD). The aim of the present study was to assess the time course and the clinical meaning of the pseudocholinesterase isozymes during an acute phase in CD. Ten healthy volunteers and 10 patients with active CD (Crohn's disease activity index, CDAI, > 200) were examined. In CD patients an acute phase treatment with prednisolone was administered for 7 weeks reaching an improvement (CDAI < 200) in 7 patients. Before initiation of steroid treatment, the isozymes C1 (controls: median 19.7%, interquartile range 16-22.2%; CD: 6.2%, 5-8%; p < 0.001) and C4 (controls: 63.5%, 59-71%; CD 81.7%, 72.9-84.7%; p < 0.001) were decreased and increased, respectively, and did not change significantly during the time of acute phase treatment. The isozymes C2 and C3 did not show any difference between controls and CD patients. Five of the patients were followed up for the subsequent 3 months of remission (CDAI < 150). During the period C1 and C4 normalized and no difference between controls and CD patients was obtained (C1: 16.4%, 15.5-20.2%; C4: 59.4%, 55.8-60.5%). Therefore, pseudocholinesterase isozymes are useful parameters in CD to to indicate active CD or long-term remission.

Acute Disease↗
PubMed1996

Effects of estradiol on circulating P-selectin.

The membrane protein P-selectin tethers leukocytes to endothelial cells (EC) and on activated platelets, and may play a role in atherosclerosis. Lower plasma levels of a soluble (c) P-selectin have recently been observed in premenopausal women compared to those in men. Given the antiatherogenic-cardioprotective effect of 17 beta-estradiol (E2), we hypothesized that E2 may down-regulate the expression of P-selectin and subsequently decrease cP-selectin levels. The effects of E2 on levels of plasma cP-selectin were evaluated during the menstrual cycle in healthy women (n = 18) and by measuring the effect of a single im injection of 10 mg E2 valerate (n = 9) or placebo (n = 10) on cP-selectin levels in healthy male volunteers. In women, the cyclic increase in serum E2 concentrations was accompanied by a decrease in cP-selectin levels from 110 ng/mL [95% confidence interval (CI), 100-137 ng/mL] in the follicular phase. The decrease reached a maximum of 13% (95% CI, 2-19%, P = 0.014) in the luteal phase. In men, cP-selectin decreased from a median of 139 ng/mL (95% CI, 113-165) to 125 ng/mL (95% CI, 97-152; P = 0.038) 4 days after E2 injection. The median baseline value of cP-selectin in the 19 male volunteers was 133 ng/mL (95% CI, 115-143 ng/mL) and was approximately 30% higher than those in the female volunteers during the midcycle (P = 0.024) and luteal (P = 0.012) phases, but was not different from that during the follicular phase. In sum, our study suggests that E2 lowers cP-selectin levels. An E2-induced decrease in cP-selectin reflects either decreased activation or damage of platelets and/or endothelial cells in vivo. Thus, our study may point to an additional mechanism for the residual antiatherogenic-cardioprotective effect of E2 that cannot be explained by its lipid-lowering effects.

Adult↗
PubMed1996

Serum levels of erythropoietin in acute Plasmodium falciparum malaria.

The pathophysiologic backgrounds of anemia in malaria are complex and multifactorial. The purpose of the present study was to measure serum concentrations of erythropoietin (EPO) and to evaluate the adequacy of EPO production in patients suffering from acute Plasmodium falciparum malaria. Fifteen patients with complicated malaria were included in the study. Serum samples were taken on the day of admission, and days 7, 14, 21 and 28. Serum EPO concentrations were measured using an enzyme-linked immunosorbent assay. The median serum EPO concentration was 15.6 mU/ml on the day of admission (range 0.5-567) mU/ml, 10.6 mU/ml (1.2-863) on day 7, 11.8 mU/ml (0.5-72.8) on day 14, 10 mU/ml (0.5-74.6) on day 21, and 8.3 mU/ml (2.2-61.6) on day 28. Inadequate EPO production was found in 46.6% of the patients on the day of admission, which increased to 67% and 68% on days 7 and 14, and reached a maximum of 80% on day 21. Almost 54% of patients had inadequate EPO production on day 28. Our data indicate inadequate EPO production in patients suffering from acute P. falciparum malaria, which might contribute to the prolonged anemia observed in these patients.

Acute Disease↗
PubMed1996

Elevated circulating P-selectin in insulin dependent diabetes mellitus.

Based on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients. The aim of this study was to compare the plasma levels of cP-selectin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays. Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p > 0.05). In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

Adolescent↗