bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-acetyl-cysteine Reduces Neointimal Thickening and Procoagulant Activity after Balloon-induced Injury in Abdominal Aortae of New Zealand White Rabbits
Authors: Eisenberg Paul , Martelli Antonietta , Orsi Patrizia , Sini Daniela , Spallarossa Paolo , Ghigliotti Giorgio , Mereto Eugenio 
Published: March 2018

Summary
Background: Procoagulant activity and oxidative stress generated by balloon injury to normal vessels promote the migration of medial smooth muscle cells and their proliferation in the intima. We hypothesised that administering levo N-acetyl-cysteine (NAC) i.v. at the time of injury, and s.c. before and after injury would reduce neointimal formation 4 weeks later and would regulate procoagulant activity in vessels with neointima undergoing ballooning a second time. Methods and Results: at the time of injury rabbits received: NAC, unfractionated heparin (HEP) or both (NAC + HEP). Neointimal thickening at 28 days, calculated as the ratio between the intimal and medial area, was attenuated after NAC, HEP and NAC+HEP by 39%, 30% and 47% respectively when compared to untreated injured animals (CONTROLS) (p 0.05). At 28 days, bound thrombin activity and platelet adhesion 1 h after a repeated balloon injury decreased in animals receiving NAC, HEP and NAC+HEP by 54%, 63% and 64% for thrombin activity (p 0.05 vs CONTROLS), and by 56%, 66% and 75% respectively for 111Indium-platelet deposition (p 0.05 vs CONTROLS). Conclusions: NAC in-vivo was effective in reducing neointimal thickening and procoagulant response after balloon injury.
Thrombin Induces the Release of Angiopoietin-1 from Platelets
Authors: Li Jian-Jun , Huang Yao-Qi , Basch Ross , Karpatkin Simon 
Published: March 2018

SummaryBlood platelets contain angiopoietin-1, a growth factor essential for blood vessel development via stabilization of proliferating endothelial cells. It has recently been reported that angiopoietin-1 can act as a vascular stability factor (Nature Medicine 6:460, 2000). In investigating the normal tissue distribution of angiopoietin-1 from surgically-removed frozen specimens by RT-PCR, we found it consistently present in platelets and megakaryocytes, usually absent in relatively non-vascular tissue: breast, colon, lung, skin, kidney, thyroid, testicle, cervix and occasionally present in tissue enriched with vasculature: prostate, endometrium, ovary, under conditions in which mRNA stability was verified by the positive detection of internal control, actin mRNA. The consistent distribution in platelets and relatively absent distribution in non-vascular normal tissue suggested that the well-known role of platelets in maintaining vascular stability, may in part be due to platelet release of angiopoietin-1 following platelet activation. In this communication we report the incidence of Ang-1 in various normal tissues and demonstrate that thrombin-treated human platelets release angiopoietin-1 in vitro.
Evidence for Platelet αIIbβ3 Activation despite Elevated Cytosolic cAMP
Authors: Riondino Silvia , Pulcinelli Fabio , Gazzaniga Pier Paolo 
Published: March 2018

SummaryCyclic nucleotides, such as cAMP, are known to inhibit the multistep cascade that results in platelet aggregation. In the present study we provide evidence that it is possible to bypass cAMP inhibitory effect on fibrinogen binding site exposure induced by the thromboxane A2 synthetic analogue U46619, the snake venom toxin convulxin, or by the direct PKC activator OAG, by concomitantly activating a Gi-coupled receptor by means of epinephrine or by inducing cytosolic calcium influx by means of ionomycin. In fact, in our study we demonstrate that, in iloprost-treated platelets, the inhibition of both platelet aggregation and fibrinogen binding was overcome by adding epinephrine or ionomycin. To further confirm this, we used the cAMP analogue dibutyryl cAMP and we obtained platelet aggregation in response to U46619, convulxin or OAG plus epinephrine. Moreover, a complete inhibition of platelet aggregation in the presence of high concentrations of cAMP was observed only in the case of U46619, while a small percentage of aggregation persisted when convulxin or OAG were used, due to the small amount of ADP that both convulxin and OAG are able to release.Since PKC inhibition didn’t allow platelet aggregation to occur in response to the concomitant activation of U46619 or convulxin, plus epinephrine or ionomycin, we can conclude that cAMP-induced inhibition of aggregation can be counteracted by the simultaneous activation of PKC in the presence of an activated Gi-coupled receptor or of an induced calcium influx.
Platelet Activation and Platelet-erythrocyte Aggregates in End-stage Renal Disease Patients on Hemodialysis
Authors: Sirolli Vittorio , Strizzi Luigi , Di Stante Silvio , Robuffo Iole , Procopio Antonio , Bonomini Mario 
Published: March 2018

SummaryActivated platelets may engage in dynamic interplay with other blood cells. We examined the evidence for platelet activation and the formation of platelet-erythrocyte aggregates in chronic hemodialysis patients. Circulating activated platelets (P-selectin/CD63-positive platelets) were higher than normal controls (p <0.001) and further increased during hemodialysis sessions, the increase being higher when patients were dialyzed with cellulosic than with synthetic membranes. We found direct evidence of uremic platelet-erythrocyte adherence in vitro and increased levels of circulating platelet-erythrocyte aggregates in dialysis patients, which represents a new observation in uremia. Platelet-erythrocyte aggregates were subject to further increase during hemodialysis, and again higher levels were found with cellulosic than synthetic membranes. This phenomenon was reproduced in vitro by both ADP and PAF, but not by either complement factor C3a or by heparin concentrations corresponding to those used for clinical hemodialysis. We conclude that platelet-erythrocyte aggregates occur in hemodialysis patients probably owing to a primary platelet activation mechanism.
Benigne Weichteiltumoren des Kopf-Hals-Bereiches im Kindes- und Jugendalter
Authors: Rendenbach C. , Precht C. , Henningsen A. , Kreutzer K. , Hauber A. M. , Köhnke R. , Schöllchen M. , Heiland M. , Rashad A. , Friedrich R. E. 
Published: March 2018

ZusammenfassungBenigne Weichteiltumoren treten mit einer Inzidenz von 300/100 000 auf. Sie sind häufig im Kopf-Hals-Bereich lokalisiert. Das klinische Erscheinungsbild ist aufgrund der vielen verschiedenen Entitäten variabel und beinhaltet durch die hier engen Lagebeziehungen oft neben einer Schwellung auch funktionelle Einschränkungen des Kau-, Schluck-, Sprech-, Hör- und Sehapparats. Neben Anamnese und körperlicher Untersuchung sind vor allem die Sonografie und Magnetresonanztomografie diagnostische Mittel. Die Therapie besteht zumeist in einer kompletten Resektion.
Neurobiologische Grundlagen von Temperament und Persönlichkeit
Authors: Rujescu D. , Watzke S. 
Published: March 2018

ZusammenfassungTemperament und Persönlichkeit sind seit jeher zentraler Bestandteil psychologischer Forschung. Während frühe Ansätze die Entstehung des Charakters in der Auseinandersetzung mit Eltern und Umwelt bzw. in Lernerfahrungen begründet sahen, entwickelte sich zeitgleich mit phänomenologisch orientierten statistischen Persönlichkeitssystemen das Interesse an der neurobiologischen Grundlage von Temperament und Persönlichkeit. Eysenck sah Persönlichkeitsmerkmale an die Aktivität spezifischer Hirnareale gebunden. Gray erweiterte diese Sicht um beteiligte Transmittersysteme. Aktuell werden die Grundlagen dieser basalen biochemischen Prozesse auf ihre jeweiligen genetischen Ursachen untersucht. Dabei zeigt sich, dass diese zum einen nur in hochkomplexen Zusammenhängen zu beschreiben sind, zum anderen aber auch nicht genetisch-deterministisch wirken. In epigenetischen Prozessen nehmen frühe Erfahrungen und Umweltfaktoren Einfluss darauf, in welchem Rahmen sich die genetische Basis in der Ausgestaltung der individuellen Persönlichkeit niederschlägt.
Wirkfaktoren psychosozialer Behandlungen bei Sucht und komorbiden psychischen Störungen
Authors: Moggi F. 
Published: March 2018

Zusammenfassung
Gegenstand und Ziel: Es werden die wichtigsten Wirkfaktoren erfolgreicher psychosozialer Behandlungen von Patienten mit einer Komorbidität von psychischen Störungen und Sucht (Doppeldiagnosen) herausgearbeitet. Material und Methoden: In den wissenschaftlichen Datenbanken PubMed, PsycINFO und Web of Science wurden neuere Metaanalysen und umfassende Übersichtsarbeiten zur Wirksamkeit psychosozialer Behandlungen bei Doppeldiagnose-Patienten gesucht und aus deren Ergebnisse das vorliegende „narrative review“ erarbeitet. Dabei wird näher auf die Studienergebnisse zu schweren und zu leichten Formen von Komorbidität eingegangen. Ergebnisse: Integrative, gestufte Behandlungsprogramme, die störungsspezifische Interventionen kombinieren, sind Kontrollgruppen (z. B. Wartegruppen, Standardbehandlungen) meistens, bzw. anderen aktiven Behandlungen (z. B. Psychoedukation) manchmal in den drei Ergebnisbereichen (Sucht, psychische Störung und Funktionsniveau) überlegen. Erfolgreiche Behandlungsprogramme enthalten meist motivierende Gesprächsführung, kognitiv-verhaltenstherapeutische Interventionen, substanzkonsumbezogene Interventionen wie Rückfallprävention oder Kontingenzmanagement und/oder Familieninterventionen. Schlussfolgerung: Die Heterogenität der Patienten-, Behandlungs-, Settings- und Ergebnismerkmale erschweren allgemeingültige Schlussfolgerungen über die Wirksamkeit psychosozialer Behandlungen. Bei Patienten mit Doppeldiagnosen sind integrierte Behandlungsangebote am erfolgversprechendsten.
Blockade of CD40/CD40 Ligand Interactions Prevents Induction of Factor VIII Inhibitors in Hemophilic Mice but Does not Induce Lasting Immune Tolerance
Authors: Reipert Birgit , Sasgary Maria , Ahmad Rafi , Turecek Peter , Schwarz Hans Peter 
Published: March 2018

SummaryPatients with severe hemophilia A frequently develop neutralizing anti-factor VIII antibodies after replacement therapy with factor VIII (FVIII). In a search for new strategies to induce immune tolerance against FVIII in these patients, we used a murine model of hemophilia A to investigate the importance of CD40/CD40 ligand (CD40L) interactions for the initiation of the anti-FVIII immune response. We focused our attention in particular on the induction of neutralizing anti-FVIII antibodies and the Th1/Th2 polarization of FVIII-specific T cells. The development of anti-FVIII antibodies was analyzed by ELISA systems (detection of total anti-FVIII antibodies) and Bethesda assays (determination of neutralizing anti-FVIII antibodies). Factor VIII-specific T cells were characterized by multiparameter flow cytometry and cytokine ELISAs for the detection of cytokine production in splenic CD4+ T cells after in vitro restimulation with FVIII. Hemophilic mice received four doses of FVIII and anti-CD40L antibody MR1 (24 h before FVIII). Subsequently mice received four doses of FVIII only. The induction of neutralizing anti-FVIII antibodies in hemophilic mice after treatment with human FVIII could be prevented completely by a blockade of CD40/CD40L interactions using MR1. Furthermore, FVIII-specific T-cell responses that included both Th1 and Th2 cells were suppressed when mice were treated with FVIII and MR1. The initial blockade of CD40/CD40L interactions was, however, not sufficient to induce a lasting immune tolerance against FVIII. The immune suppression was abolished and both neutralizing anti-FVIII antibodies and FVIII-specific T cells developed when treatment with FVIII was continued after the omission of MR1. In addition, there were no alterations in the Th1/Th2 polarization induced by the initial blockade of CD40/CD40L interactions.
Low Molecular Weight Heparin and Warfarin in the Treatment of Patients with Antiphospholipid Syndrome during Pregnancy
Authors: Dulitzki Mordechai , Langevitz Pnina , Livneh Avi , Kenett Ron , Many Amira , Pauzner Rachel 
Published: March 2018

SummaryFifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient’s consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.
Complexes between Activated Protein C and Protein C Inhibitor Measured with a New Method
Authors: Strandberg Karin , Astermark Jan , Björgell Ola , Becker Charlotte , Nilsson Paul , Stenflo Johan 
Published: March 2018

SummaryA first clinical evaluation has been made of the performance of a newly devised immunofluorometric assay for measuring plasma concentrations of activated protein C (APC) in complex with protein C inhibitor (PCI). The method was compared with testing for other markers of hypercoagulability in a case-control study comprising 123 patients with clinical suspicion of deep vein thrombosis (DVT). The diagnosis was confirmed by ascending phlebography, and the thrombotic burden estimated with a newly developed scoring system. Receiver operating characteristics (ROC) curves calculated to demonstrate the discriminatory capacity of the methods, showed the area under the curves (AUCs) to be similar for the APC-PCI and D-dimer methods. However, in contrast to the D-dimer method, the APC-PCI method measures a well-defined analyte, a prerequisite for reliable comparisons of future clinical studies. The APC-PCI method appears to be particularly useful as a marker for detection of recently developed proximal thrombi.
A Naturally Occurring Point Mutation in the β3 Integrin MIDAS-like Domain Affects Differently αvβ3 and αIIbβ3 Receptor Function
Authors: Melchior Chantal , Chen Ping , Ammerlaan Wim , Lecompte Thomas , Kaplan Cécile , Kieffer Nelly , Morel-Kopp Marie-Christine 
Published: March 2018

SummaryWe have investigated the effect of a new Leu196Pro mutation, identified in the MIDAS-like domain of the β3 integrin subunit in a patient with type II Glanzmann thrombasthenia, on β3 integrin receptor function. Expression of the mutant β3Pro196 subunit in CHO cells, either associated with recombinant human αIIb or αv, resulted in normal biosynthesis of β3 and heterodimerization with αv or IIb, but selectively interfered with αIIbβ3 maturation and transport to the cell surface. Functional analysis of the β3 mutant receptors revealed strong inhibition of αvβ3-mediated cell spreading on immobilized fibrinogen, focal contact formation, p125FAK phosphorylation and fibrin clot retraction, as opposed to normal αIIbβ3-mediated cell interaction with immobilized fibrinogen, focal contact translocation and signaling. In contrast, antibody- or DTT-activated mutant αIIbβ3 was unable to bind soluble fibrinogen or the ligand mimetic PAC-1 monoclonal antibody, but underwent a conformational change following RGD peptide binding as demonstrated by AP5-LIBS epitope expression. These results suggest that (1) the highly conserved TL196T motif in the β3 integrin subunit is located in a domain structurally important for the exposure of a functional binding site for soluble fibrinogen; and (2) that the MIDAS-like contact site in β3 is not involved in αIIbβ3-mediated cell adhesion to immobilized fibrinogen, while it is essential for αvβ3-mediated interaction with this ligand.
A Frameshift Mutation in the Human Fibrinogen Aα-chain Gene (Aα [499] Ala Frameshift Stop) Leading to Dysfibrinogen San Giovanni Rotondo
Authors: Vecchione Gennaro , Santacroce Rosa , D’Angelo Francesca , Casetta Bruno , Papa Maria Luisa , Grandone Elvira , Minno Giovanni Di , Margaglione Maurizio 
Published: March 2018

SummaryWe have investigated a 53-yr-old asymptomatic white man with decreased functional, but not immunologic, fibrinogen plasma levels together with prolonged thrombin and reptilase times, detected through routine coagulation studies prior to a surgical procedure. A new heterozygous single nucleotide deletion (C) at position Ala499 within the Aα-chain gene was identified, which predicted changes of the corresponding aminoacids encoded by the subsequent portion of the exon V and the appearance of a premature stop codon at position 518 (A [499]Ala frameshift stop). The new dysfunctional fibrinogen, San Giovanni Rotondo variant, was confirmed in vivo by SDS-PAGE analysis of HPLC-purified fibrinogen chains. Mass spectrum examination of the abnormal HPLC-purified peak gave an estimated mass (56,088 Da) similar to that predicted by DNA analysis of the mutated Aα-chain gene (56,088 Da) and, after tryptic digestion, the truncated Aα-chain was shown only in the propositus, who also carried normal Aα-chain. In addition, mass spectrum analysis of the tryptic digest of the abnormal chain confirmed the presence of a new and unpaired cysteine at the last position that was predicted to form a disulfide bridge with human serum albumin. Immuno-blot analysis confirmed that fibrinogen San Giovanni Rotondo variant, but not normal fibrinogen, contained substantial amounts of albumin. Present findings confirm that truncated Aα-chain lacking part of the terminal domain may be incorporated into mature fibrinogen molecules and normally secreted in the bloodstream.
The Ability of Poloxamers to Inhibit Platelet Aggregation Depends on their Physicochemical Properties
Authors: Ahmed Fariyal , Alexandridis Paschalis , Shankaran Harish , Neelamegham Sriram 
Published: March 2018

SummaryPoloxamers, block copolymers of polyethylene glycol (PEG) and polypropylene glycol (PPG), are thought to reduce cell-cell adhesion during vascular disorders. We examined how the amphiphilic nature of these polymers may contribute to their ability to inhibit ADP-induced platelet aggregation. Four Poloxamers (184, 188, 335 and 338) with varying PEG and PPG block lengths were examined. Of these, Poloxamer 184 at 2 mM markedly inhibited platelet aggregation. We observed that: i) Typically, less than 10% of the platelet surface is covered by Poloxamers, and greater than 99% of the polymer either remains in solution or binds soluble components in blood plasma. ii) Increasing the PEG side-chain length does not significantly augment the ability of Polox-amers to inhibit platelet aggregation. iii) Poloxamer 184, but not Polox-amers 188 and 335, significantly reduces the ability of stimulated platelets to bind fibrinogen and antibody PAC-1. The study demonstrates that the physical adsorption of some Poloxamers may allow them to inhibit platelet aggregation. The inhibition mechanism involves either binding of Poloxamers to platelet GPIIb-IIIa or inhibition of cellular activation pathways.
The Type of Factor VIII Deficient Plasma Used Influences the Performance of the Nijmegen Modification of the Bethesda Assay for Factor VIII Inhibitors
Authors: Giles Alan , Samis John , Verbeek Kitty , Mensink Ewald , Novákovà Irena , Verbruggen Bert 
Published: March 2018

SummaryWe have investigated the influence of the type of factor VIII deficient plasma used on the assay results of the Nijmegen modification of the Bethesda method for factor VIII inhibitors. Immuno depleted factor VIII deficient plasmas, lacking besides factor VIII also von Willebrand factor, gave decreased inhibitor titres compared to assay results with factor VIII deficient plasmas containing von Willebrand factor suggesting the need of the latter in the test system for the stability of factor VIII:C. Moreover the performance of the assay with immuno depleted plasma was contaminated in a certain type of this plasma by the presence of a factor VIII:C inhibitor. Chemically depleted factor VIII deficient plasma appeared to give falsely elevated titres when used in combination with other types of deficient plasmas as substrate plasma in the factor VIII:C assay due to the presence of activated factor Va in the preparation. Suggestions are described with respect to the observed limitations in order to obtain reliable results.
Gerinnungsanalyse bei Transplantationspatienten
Authors: Riess H. , Loew A. 
Published: March 2018

ZusammenfassungBei Patienten nach Organtransplantation können sich aufgrund der zur Transplantation führenden Grundkrankheit als auch transplantationsbedingt sowohl vorbestehende Hämostasestörungen maskieren als auch entwickeln. Da die Leber den Hauptbildungsort für die Gerinnungsfaktoren darstellt, prädestiniert die orthotope Lebertransplantation für den Erwerb bzw. Verlust eines genetisch determinierten Gerinnungsdefektes. Hier kann es in der Gerinnungsdiagnostik zur Diskrepanz zwischen funktionellen Tests im Plasma und molekularbiologischen Befunden kommen, sofern diese wie üblich aus kernhaltigen Zellen des peripheren Blutes erhoben werden.Die Seltenheit der meisten Defekte und die fehlenden Konsequenzen bei Nachweis der häufigeren Gerinnungsstörungen führen dazu, dass kein prinzipielles Screening vor oder nach Transplantation gefordert wird. Der Umstand einer zur Transplantation führenden Grundkrankheit ist ebenso wie die Transplantation selbst in die Interpretation von Befunden einzubeziehen.
Faktor-Xa-Inhibition in der interventionellen Kardiologie
Authors: Peter K. , Bode C. , Ahrens I. 
Published: March 2018

ZusammenfassungEine zwei-oder dreifache antithrombozytäre Therapie kombiniert mit einer systemischen Antikoagulation, wie in der interventionellen Kardiolgie häufig angewandt, kann das Blutungsrisiko deutlich erhöhen. Wie vor kurzem gezeigt, geht ein erhöhtes Blutungsrisiko mit einer höheren Rate ischämischer Ereignisse sowie einer höheren Mortalität einher. Letzteres unterstreicht die Notwendigkeit für die Entwicklung neuer Antikoagulanzien mit besserem Sicherheitsprofil. Die zentrale Position der Gerinnungsfaktoren IIa und Xa im Gerinnungssystem machen diese zu idealen Zielen für die Entwicklung von Antikoagulanzien. Unfraktioniertes Heparin (UFH) bewirkt eine variable Inhibition beider Faktoren. Im Vergleich zu UFH weisen die niedermolekularen Heparine (NMH) vorteilhafte pharmakologische Eigenschaften auf, NMH zeigen eine stärkere Selektivität für die Inhibierung von Faktor Xa. Eine Gruppe neuer Antikoagulanzien ermöglicht die selektive Inhibition von Faktor Xa. Aktuelle klinische Studien mit einem indirekten selektiven Faktor-Xa-Inhibitor zeigen überzeugende Ergebnisse bei Patienten mit akutem Koronarsyndrom (ACS) und STStreckenhebungs-Myokardinfarkt (STEMI) sowie ACS und Non-STEMI. Dieser Artikel diskutiert die pharmakologischen Eigenschaften der indirekten selektiven Faktor-Xa-Inhibitoren Fondaparinux und Idraparinux sowie der direkten selektiven Faktor-Xa-Inhibitoren DX-9065a und Otamixaban zusammen mit deren Einsatz in klinischen Studien in der interventionellen Kardiologie.