bluuebunny/crossref_metadata_2025_split huggingface dataset:
Could Lipid Profile be Used as a Marker of Autonomous Cortisol Secretion in Patients with Adrenal Incidentalomas?
Authors: Mintziori Gesthimani , Georgiou Thomas , Anagnostis Panagiotis , Adamidou Fotini , Efstathiadou Zoe , Panagiotou Athanasios , Kita Marina 
Published: July 2018

AbstractAdrenal incidentalomas (AIs) have been associated with an increased risk of metabolic syndrome and dyslipidemia, though evidence regarding the latter is limited. Lipid abnormalities in patients with AIs have been associated with subclinical hypercortisolism. The current study aims to test whether lipid profile in patients with AIs predicts “autonomous cortisol secretion” (ACS). Patients with AIs found on either computerized tomography (CT) or magnetic resonance imaging (MRI), were included in a prospective cohort study. All patients were followed up for at least three years. Alterations in their hormonal and lipid profiles were recorded. Ninety-four patients (69 women) harboring 111 AIs were included. There were no differences between patients with ACS and those without, with respect to their baseline lipid profile [total cholesterol, low-density-lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C] and blood pressure (systolic and diastolic). Non-HDL-C concentrations decreased over time (Repeated Measures ANOVA, p=0.013), despite patients’ body mass index (BMI) remaining unchanged. Logistic regression analysis revealed that the only predictor of ACS was the size of AIs, as calculated by CT or MRI. The current study demonstrated that lipid profile at baseline or during follow-up cannot predict ACS in patients with AIs. However, larger AIs may have a greater probability of ACS.
Durch die kontinuierliche Blutdruckmessung lässt sich ein transienter orthostatischer Blutdruckabfall bei idiopathischer REM-Schlaf-Verhaltensstörung nachweisen
Authors: Schiefer J. , Reetz K. , Haubrich C. , Maier A. , Dogan I. , Heller J. , Reh K. , Mannartz V. , Fandyeyeva V. , Koch J. , Schulz J. 
Published: July 2018

Ziel der Studie Es gibt wenige Daten zum orthostatischen Blutdruck (BD) Verhalten und Veränderungen der Herzratenvariabilität (HRV) bei idiopathischer REM-Schlaf-Verhaltensstörung (iRBD). Unsere Hypothese war, dass orthostatische BD Veränderungen vorübergehend sind.
Methodik Wir untersuchten 16 männliche iRBD Patienten und 15 altersgematchte männliche Kontrollprobanden (HC) im Hinblick auf eine Dysautonomie, HRV und kontinuierliche BD Messung während der Kipptischuntersuchung.
Ergebnisse Die BD Abfälle in den ersten 5 Minuten Stehzeit waren bei iRBD Patienten signifikant größer. IRBD Patienten hatten häufiger eine reduzierte respiratorische Sinusarrhythmie (RSA).
Schlussfolgerungen Mittels kontinuierlicher BD Messung ließen sich transiente orthostatische BD Abfälle bei iRBD detektieren. Longitudinale Daten werden zeigen, ob diese Änderungen Hinweise für eine periphere sympathoneurale Dysfunktion darstellen und frühe Marker einer späteren orthostatischen Hypotonie sein können.
Intermittent Regional Therapy with rt-PA is not Superior to Systemic Thrombolysis in Deep Vein Thrombosis (DVT) - a German Multicenter Trial
Authors: Schwieder G , Grimm W , Siemens H J , Flor B , Hilden A , Gmelin E , Friedrich H J , Wagner T 
Published: July 2018

SummaryIn a prospective and randomized multicenter trial the efficacy of intermittent regional and systemic thrombolytic therapy for DVT was evaluated. 137 patients with phlebographically confirmed acute DVT above the calf region were treated with 20 mg of rt-PA for 4 h each day. Thrombolysis was applied either locally via a dorsal pedal vein of the firmly bandaged affected leg or systemically using a cubital vein. Treatment lasted for 4-7 days, and during this time unfractionated heparin was applied continuously with the dosage adjusted according to aPTT (1.5-2.0 times the normal value). A second phlebography was performed within 24 h after the end of treatment. Results were evaluated by an independent radiologist who was unaware of the treatment givenSignificant thrombolytic results (e.g. lysis of more than 50% of the original thrombus and complete recanalization of all affected veins) were reached in only 1/3 of all patients. Rates of recanalization did not differ in both groups and bleeding complications occurred in 26.5%. We conclude that intermittent local or systemic application of 20 mg rt-PA seems to be ineffective in the treatment of DVT
Variation of Phylioquinone (Vitamin K1) Concentrations in Hemodialysis Patients
Authors: Kohlmeier Martin , Saupe Jörg , Drossel Hans-Joachim , Shearer Martin J 
Published: July 2018

SummaryIntra- and interindividual variation of phylloquinone (vitamin K1) concentrations was investigated by repeat analysis of serum from 28 hemodialysis patients with different apolipoprotein E genotypes. Phylloquinone concentrations ranged from 0.1 to 9.0 nM, with a mean of 1.08 nM (standard deviation 1.90 nM).Most of the variation in serum phylloquinone concentrations was due to differences between patients; the ratio of intra-to interindividual variation was 0.17. Serum triglyceride concentrations and apoE genotype together accounted for 64% of interindividual variation; in contrast, only 6% of intraindividual variation could be attributed to differences in triglyceride concentrations.The small residual variance implies that different phylloquinone consumption levels contributed relatively little to the variation of serum concentrations (<36% of interindividual variance). The results suggest that individual disposition is a more important determinant of serum phylloquinone concentrations than dietary phylloquinone intake.
Characterization of the Interaction of a Complex of Tissue-type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 with Rat Liver Cells
Authors: Kuiper J , Otter M , Voorschuur A H , Zonneveld A J van , Rijken D C , Berkel Th J C van 
Published: July 2018

SummaryThe present study was undertaken in order to determine the recognition site for tissue-type plasminogen activator-plasminogen activator inhibitor type 1 [t-PA-PAI-1] complexes in rat liver in vivo and in vitro. After intravenous injection into rats t-PA-PAI-1 complexes were rapidly removed from the plasma and the liver took up 80% of the injected dose. Within the liver parenchymal and endothelial liver cells contributed mainly to the uptake of t-PA-PAI-1, and were responsible for 62% and 24% of the liver uptake, respectively. The interaction of t-PA- PAI-1 with isolated rat parenchymal liver cells was of high affinity (Kd 17 nM). A well-known antagonist of the α2-macroglobulin receptor (α2MR/low-density lipoprotein receptor-related protein (LRP), GST-39kDa protein (GST-39kDaP) efficiently inhibited the binding (IC50 0.7 nM) of t-PA-PAI-1 to rat parenchymal liver cells. The interaction of t-PA-PAI-1 with LRP on rat parenchymal liver cells was not Ca2+-dependent and is most probably mediated by a specific determinant on PAI-1, since an anti-PAI-1 monoclonal antibody inhibited the binding of t-PA-PAI-1, where as free t-PA did not. The binding of t-PA-PAI-1 to rat hepatocytes could not be inhibited by a complex of plasmin and α2-antiplasmin nor by various other ligands of LRP like β-VLDL and lactoferrin. Binding of t-PA-PAI-1 to rat parenchymal liver cells was followed by internalization and subsequent degradation in the lysosomal compartment.It is concluded that parenchymal and endothelial liver cells mediate the removal of t-PA-PAI-1 complexes from the circulation. LRP on rat parenchymal liver cells is responsible for the uptake and degradation of t-PA-PAI-1 and may therefore be important for the regulation of the t-PA levels in the circulation.
A Comparison of the Effect of Decorsin and Two Disintegrins, Albolabrin and Eristostatin, on Platelet Function
Authors: McLane Mary Ann , Gabbeta Jagadeesh , Rao A Koneti , Beviglia Lucia , Lazarus Robert A , Niewiarowsk Stefan 
Published: July 2018

SummaryNaturally-occurring fibrinogen receptor antagonists and platelet aggregation inhibitors that are found in snake venom (disintegrins) and leeches share many common features, including an RGD sequence, high cysteine content, and low molecular weight. There are, however, significant selectivity and potency differences. We compared the effect of three proteins on platelet function: albolabrin, a 7.5 kDa disintegrin, eristostatin, a 5.4 kDa disintegrin in which part of the disintegrin domain is deleted, and decorsin, a 4.5 kDa non-disintegrin derived from the leech Macrobdella decora, which has very little sequence similarity with either disintegrin. Decorsin was about two times less potent than albolabrin and six times less potent than eristostatin in inhibiting ADP- induced human platelet aggregation. It had a different pattern of interaction with glycoprotein IIb/IIIa as compared to the two disintegrins. Decorsin bound with a low affinity to resting platelets (409 nM) and to ADP-activated platelets (270 nM), and with high affinity to thrombin- activated platelets (74 nM). At concentrations up to 685 nM, it did not cause expression of a ligand-induced binding site epitope on the (β3 subunit of the GPIIb/IIIa complex. It did not significantly inhibit isolated GPIIb/IIIa binding to immobilized von Willebrand Factor. At low doses (1.5-3.0 μg/mouse), decorsin protected mice against death from pulmonary thromboembolism, showing an effect similar to eristostatin. This suggested that decorsin is a much more potent inhibitor of platelet aggregation in vivo than in vitro, and it may have potential as an antiplatelet drug.
HES 200/0.5 Is not HES 200/0.5
Authors: Treib Johannes , Haass Anton , Pindur Gerhard , Seyfert Ulrich T , Treib Wolfgang , Grauer Markus T , Jung Friedel , Wenzel Ernst , Schimrigk Klaus 
Published: July 2018

SummaryThe plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch.10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7.After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p<0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs.8.6 mg/ml). Hematocrit was lowered more (-30,5 vs. -23,5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p <0.01), which exceeded the dilution effect.The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.
The Effect of the Synthetic Pentasaccharide SR 90107/ORG 31540 on Thrombin Generation Ex Vivo Is Uniquely due to ATIII-Mediated Neutralization of Factor Xa
Authors: Lormeau J C , Herault J P 
Published: July 2018

SummaryThe inhibition of thrombin generation (TG) was studied in plasma from human volunteers after single subcutaneous administrations of 4000, 8000 or 12,000 anti-Xa units (i.e., 6, 12 or 18 mg) of the synthetic pentasaccharide (SR 90107/ORG 31540) (SP).SP impaired TG in plasma for up to 18 h after injection, and the time-courses of TG and factor Xa inhibitions were similar.In untreated plasma supplemented in vitro with SP to obtain the same anti-Xa activity as in ex vivo samples, equivalent TG inhibitions were observed thus showing that no transformed SP molecules were involved in the TG inhibition ex vivo.Functional as well as immunological assay of TFPI indicated that subcutaneous injection of 12,000 anti-Xa units of SP did not induce any TFPI release, whereas under the same conditions, 13,000 IU of Fraxiparine® produced a significant rise of TFPI in plasma.The plotting of TG inhibition versus SP concentration could be fitted with a good correlation (r = 0,94) to the graphical representation linking [ATIII-SP] to [SP].These results demonstrate that following subcutaneous administration to man, SP inhibits TG ex vivo and likely in vivo exclusively through the same selective ATIII-mediated inhibition of factor Xa as the one elicited in vitro.
Inhibition of Factor X Activation at Extracellular Matrix of Fibroblasts During Flow Conditions: A Comparison Between Tissue Factor Pathway Inhibitor and Inactive Factor VIIa
Authors: Valentin Sanne , Reutlingsperger Chris P M , Nordfang Ole , Lindhout Theo 
Published: July 2018

SummaryTissue factor pathway inhibitor (TFPI) is a naturally occurring factor Xa-dependent inhibitor of factor VIIa/tissue factor activity. In the present study, we examined the importance of the TFPI C-terminus and 3rd Kunitz-like domain for the inhibitory capacity of TFPI towards factor VIIa/tissue factor-catalyzed factor X activation and compared the inhibition with that of inactivated factor VIIa (factor VIIai). The extracellular matrix of fibroblasts, mounted in a parallel-plate flow chamber, were perfused with reaction mixtures that contained factors X, VIIa, and varying amounts of TFPI or factor VIIai. Inhibition was evaluated from the time course of factor Xa production at the outlet of the flow chamber. The factor VIIa/tissue factor-catalyzed factor Xa production was inhibited by factor VIIai and compatible with a direct competition between factor VIIai and factor VIIa for tissue factor. In contrast, TFPI showed a progressive inhibition of factor Xa production; the initial rate of factor X activation, however, was not inhibited by TFPI. Inhibition of factor Xa generation already in progress was seen for TFPI but not factor VIIai. In both cases we found that the truncated TFPI variants were as potent as full length TFPI. As to the stability of the enzyme- inhibitor complexes, TFPI/Xa/VIIa/tissue factor and factor VIIai/tissue factor, marked differences were observed. About 60% of the factor VIIa/tissue factor activity was recovered from the truncated TFPI/Xa/VIIa/tissue factor complex after 150 min of perfusion with reaction mixtures that contained factors X and VIIa. In contrast, full length TFPI did not dissociate from the complex, nor could factor VIIai be displaced by a large excess of factor VIIa.
An Amino Acid Polymorphism in Histidine-rich Glycoprotein (HRG) Explains 59% of the Variance in Plasma HRG Levels
Authors: Hennis B C , Boomsma D I , van Boheemen P A , Engesser L , Kievit P , Dooijewaard G , Kluft C 
Published: July 2018

SummaryA pedigree-based maximum likelihood method developed by Lange et al. (12) was used to study the contribution of a newly defined di-allelic polymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritability of 70%, an age effect of 3% and an effect of individual environmental factors of 27%. These results are remarkably similar to the results found in a previous parent-twin study in which a heritability of 69% and an effect of random environment of 31% was found. The overall genetic influence in the present study can be subdivided into an effect of 59% by the HRG phenotype and 11% by residual genetic factors. The influence of the HRG phenotype of 59% can entirely be explained by adding up the effect of the two alleles that make up the phenotype. These results indicate a codominant inheritance pattern of HRG levels in which the genetic influence can almost completely be ascribed to the additive effect of the di-allelic HRG locus whereas only a small part is due to other loci.
Modulation of Urokinase-type Plasminogen Activator Gene Expression by Inflammatory Cytokines in Human pre-B Lymphoma Cell Line RC-K8
Authors: Niiya Kenji , Shinbo Masahiro , Ozawa Tetsuo , Hayakawa Yumiko , Sakuragawa Nobuo 
Published: July 2018

SummaryWe examined the effects of inflammatory cytokines, such as interleukin-lα (IL-lα), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ) and lipopolysaccharide (LPS), on the urokinase-type plasminogen activator (uPA) gene expression in RC-K8 human pre-B lymphoma cells. Recombinant IL-1α, recombinant IL-1β and LPS but not recombinant IL-6, recombinant TNFα and TGFβ dose-dependently increased uPA accumulation in the conditioned medium. Northern blot analysis revealed that uPA mRNA levels rapidly increased with a peak induction at 2 h after stimulation with IL-lα and IL-1β, but uPA mRNA increase by LPS began at 9 h after stimulation and the increase was maintained until the experiment ended at 24 h. These responses were independent of de novo synthesis, rather amplified in the presence of a protein synthesis inhibitor. The effects by IL-1α and IL-1β were prevented by addition of anti-IL-1α and anti-IL-1β neutralizing antibodies, respectively. In contrast, both antibodies did not prevent LPS-induced uPA gene expression. Therefore, it is unlikely that the effect by LPS is through induction of IL-1. Both IL-1α and IL-1 β rapidly activated uPA gene transcription, but not increased stability of uPA mRNA. These results suggest that both IL-1α and IL-1 β cause a rapid activation of uPA gene transcription in which de novo protein synthesis is not required and that LPS induces uPA gene expression independently of the IL-1 pathway. These modulations of uPA production by inflammatory mediators may be implicated in tumor growth and metastasis.
Peripheral Blood Monocyte Synthesis of Plasminogen Activator Inhibitor 2 in Response to Native and Modified LDL
Authors: Ritchie Helen , Jamieson Alec , Booth Nuala A 
Published: July 2018

SummaryFibrin deposition is a characteristic feature of the atherosclerotic plaque. The balance of fibrinolytic activity is modulated by plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs). We examined expression of components of the fibrinolytic system by peripheral blood monocytes following stimulation by native LDL and LDL modified by acetylation, copper oxidation or minimal modification. Monocytes responded to LDL stimulation by increased production of PAI-2, with no corresponding increase in u-PA. PAI-1 was detected but did not change relative to untreated control; u-PA was undetectable in all samples. Native LDL consistently upregulated PAI-2; this stimulation was not inhibited by inclusion of antioxidants. Acetylated, copper oxidized and minimally modified LDLs increased production of PAI-2, but the ability to stimulate PAI-2 synthesis varied between preparations of modified LDL. Increased levels of PAI-2 in a local environment such as the artery wall may promote fibrin persistence.
Procoagulant Albumin Increases Vascular Endothelial Cell Prostacyclin Secretion
Authors: Gubler David B , Ahlstrom Chad R , Liu Lihua , Zhou Jin-Feng , Parker Charles J , Rodgers George M 
Published: July 2018

SummaryVascular endothelium regulates multiple aspects of platelet function through secretion of a variety of substances, including von Willebrand factor, nitric oxide, and prostacyclin (PGI2). The objective of this study was to determine whether procoagulant albumin (P-AI), a modified form of albumin present in normal human plasma could modulate endothelial cell secretion of these substances. P-AI did not affect constitutive secretion of von Willebrand factor or nitric oxide, but did increase PGI2 secretion in a time- and concentration-dependent manner. Pretreatment of endothelial cells with aspirin, or use of suramin, a broad- specificity inhibitor, prevented the response to P-AI. Prostaglandin H synthase-2 contributed to the P-AI-induced PGI2 secretion. These results indicate that in addition to inducing tissue factor activity and reducing protein C activation and fibrinolysis, P-AI also modulates vascular endothelial cell PGI2 secretion, and potentially, platelet function.
Inhibition of Thrombus Formation by Endothelin-1 in Canine Models of Arterial Thrombosis
Authors: Leadley Robert J , Humphrey William R , Erickson Laurence A , Shebuski Ronald J 
Published: July 2018

SummaryThe effect of enclothelin-l (ET-1) on thrombus formation in vivo was evaluated in two well-established canine models of coronary artery thrombosis. First, the possible antithrombotic effect of ET-1 was examined using the cyclic flow reduction (CFR) model of coronary artery stenosis, vascular endothelial cell and intimal smooth muscle cell injury, and periodic acute platelet thrombus formation. Using a rating system of 0 (no inhibition) to 3 (complete inhibition), ET-1 administration at 0.1, 0.5, and 1.0 μg/kg, i.v. bolus, produced scores of 1.0 ± 0.2 (n = 10), 1.8 ± 0.4 (n = 8), and 2.1 ± 0.3 (n = 7), respectively. ET-1 injection inhibited ex vivo platelet aggregation induced by ADP and U-46619 by 30-60%. When aspirin was administered at 5 mg/kg prior to ET-1 administration at 0.5 pg/kg, ET-1 produced a CFR rating of 2.7 ± 0.2 (n = 6). However, higher dose aspirin (30 mg/kg, i.v.) significantly inhibited the antithrombotic effect of ET-1 (0.5 ± 0.5, n = 4). The antithrombotic effect of ET-1 was also examined using an electrolytic injury model of arterial thrombosis. The time required to produce an occlusive thrombus during the experiments in which ET-1 was administered at 10 and 20 ng kg-1 min-1 was 77 ± 15 (p <0.08) and 105 ± 16 min (p <0.05), respectively, compared to 44 ± 5 min when vehicle was infused. Cardiovascular changes following occlusion were not significantly different between dogs given ET-1 and those given vehicle, suggesting that elevated plasma levels of ET-1 did not exacerbate the adverse effects of coronary occlusion. In addition, plasma ET-1 levels were elevated significantly after occlusion in the dogs given vehicle (from 7.4 to 12.4 pg/ml). Taken together, these data provide further evidence to support the notion that ET-1 release during ischemia may be involved in a protective mechanism that impedes thrombus formation in the stenosed coronary artery.
Contribution of a New, Rapid, Individual and Quantitative Automated D-Dimer ELISA to Exclude Pulmonary Embolism
Authors: de Moerloose Philippe , Desmarais Sylvie , Bounameaux Henri , Reber Guido , Perrier Arnaud , Dupuy Georges , Pittet Jean-Louis 
Published: July 2018

SummaryThe performance of a new automated ELISA for a rapid, individual and quantitative measurement of plasma D-dimer (VIDAS D-dimer) has been evaluated. First, a study of 100 patients was performed in order to choose the best couple of antibodies in comparison with an already clinically validated ELISA. Then the results were certified in a prospective study including 195 consecutive patients suspected of pulmonary embolism (PE). For a cut-off level of 500 ng/ml VIDAS D-dimer showed a sensitivity of 100% (95% confidence interval 92-100), a specificity of 37.6%, a negative predictive value of 100% (95% CI 93.3-100) and a positive predictive value of 33.1%. During a 6 months’ follow-up no patient (95% CI 0-6.4) with D-dimer <500 ng/ml presented a new suspicion of venous thromboembolic disease. These results suggest that this rapid and single-dose ELISA provides a very useful tool for the clinician to exclude on a day-to-day basis the diagnosis of PE.