bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Efficacy of Platelet Glycoprotein IIb/IIIa Antagonist in Blocking Platelet Function in Plasma of Patients with Heparin-induced Thrombocytopenia
Authors: Mak Koon-Hou , Brooks Linda , Topol Eric , Kottke-Marchant Kandice 
Published: March 2018

SummaryHeparin-induced thrombocytopenia (HIT) is an important complication following administration of heparin. Platelet activation and aggregation induced by heparin/platelet factor 4/immunoglobulin complexes are thought to be the underlying mechanism for this condition, so it was hypothesized that abciximab (a humanized murine monoclonal antibody directed against the glycoprotein IIb/IIIa receptor) would prevent heparin-induced platelet aggregation and activation in plasma from patients with HIT. Platelet aggregation was tested in vitro with platelet-poor plasma (obtained from 23 patients with HIT), platelet-rich plasma (from normal donors with known reactivity), heparin (0.5 U/ml), and ascending doses of abciximab (0.07-0.56 μg/ml). The ability of abciximab to prevent platelet activation was also evaluated using flow cytometry (P selectin expression, mepacrine release, microparticle formation) and platelet factor 4 immunoassay. In vitro, abciximab inhibited heparin-induced platelet aggregation in a dose-dependent fashion (IC50 0.103 μg/ml) and inhibited microparticle formation, the expression of P-selectin, release of mepacrine and platelet factor 4. These findings suggest that abciximab may be useful in treatment of patients with HIT and warrants further clinical evaluation.
Effect of the Antioxidants Selenium and Beta-carotene on HIV-related Endothelium Dysfunction
Authors: Seigneur M. , Blann A. D. , Renard M. , Resplandy F. , Amiral J. , Guérin V. , Boisseau M. R. , Conri C. , Constans J. 
Published: March 2018

SummaryPatients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-sero-positive subjects with 100 μg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers.The non-supplemented patients experienced increases in von Wille-brand factor and soluble thrombomodulin (both p < 0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene.Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.
Acute Pulmonary Embolism: Impact of Selection Bias in Prospective Diagnostic Studies
Authors: Prins M.H. , Büller H.R. , Banga J.D. , Hartmann I.J.C. ,   the ANTELOPE study group
Published: March 2018

SummaryWe evaluated selection bias in a prospective study of 1162 consecutive patients with suspected pulmonary embolism. Of these, 983 were eligible, and 627 could actually be included. During two months extensive data were collected on all non-included patients. Finally, our patient characteristics were compared with those of the PIOPED study (1990) and the study of Hull et al. (1994). Compared with included patients, the non-included patients had more often non-diagnostic V/Q scans (50% vs. 36%, p <0.01) and were more often already hospitalized (31% vs. 22%, P = 0.04). The subgroup of patients not included due to refusal or inability to give informed consent (IC) was older (mean age 61 vs. 53 years, P <0.01), more often suffered from malignancies (26% vs. 11%, P <0.01) and frequently had non-diagnostic V/Q scans (57%) as compared to included patients. In our study, 54% of all patients screened was eventually included versus 27% in the PIOPED study. In the PIOPED study patients who had contra-indications for pulmonary angiography were excluded, while in the study of Hull et al. those with inadequate cardiorespiratory reserve were excluded. In studies on new diagnostic technologies, patient selection bias does occur. The potential for such a selection bias should be taken into account when diagnostic strategies are devised to improve their generalizability and acceptability.
Differential Involvement of the P2Y1 and P2YT Receptors in the Morphological Changes of Platelet Aggregation
Authors: Eckly Anita , Gendrault Jean-Louis , Hechler Béatrice , Cazenave Jean-Pierre , Gachet Christian 
Published: March 2018

SummaryThe relative contributions of the P2Y1 and P2YT receptors to the morphological changes induced in platelets by ADP or ADP-releasing agonists were assessed using two P2 antagonists, A2P5P and ARC67085, selective for P2Y1 and P2YT, respectively. The P2Y1 receptor was found to be involved in i) the centralization of secretory granules elicited by ADP, ii) the formation of filopodia induced by released ADP in weakly activated platelets and iii) actin polymerization and the cyto-skeletal translocation of cdc42, rac1 and rhoA, in an integrin IIb 3 dependent manner, in ADP-stimulated platelets. In contrast, the P2YT receptor was shown i) to be essential for the formation of stable macro-aggregates, ii) to enhance actin polymerization and the cytoskeletal translocation of small GTPases, probably through amplification of platelet aggregation, and iii) not to be involved in the early steps of platelet activation since its blockade did not affect the cytoskeletal translocation of rhoA.
Effects of Diets Containing Olive Oil, Sunflower Oil, or Rapeseed Oil on the Hemostatic System
Authors: Kratz Mario , Neufeld Margitta , Erren Michael , Nofer Jerzy-Roch , Schulte Helmut , Nowak-Göttl Ulrike , Assmann Gerd , Wahrburg Ursel , Junker Ralf 
Published: March 2018

SummaryVarious studies have already shown that the fatty acid composition of dietary fat has different effects on hemostasis and platelet function. However, knowledge on this topic is incomplete. In the present study, fifty-eight healthy students received either a 4-week rapeseed oil [high content of monounsaturated fatty acids (MUFA) and high n-3/n-6 PUFA ratio], an olive oil (high content of MUFA, low n-3/n-6 PUFA ratio) or a sunflower oil (low content of MUFA, low n-3/n-6 PUFA ratio) diet. In each group, effects on hemostatic parameters were compared with a wash-in diet rich in saturated fatty acids with respect to intermediate-time effects on the hemostatic system and platelet function. With the olive oil diet, a reduction of coagulation factors VIIc, XIIc, XIIa, and Xc was found, whereas sunflower oil led to lower values of coagulation factors XIIc, XIIa, and IXc. In all study groups levels of plasmin-α2-antiplasmin were lower in week 4 than at baseline. Lower fibrinogen binding on platelets was found after the sunflower oil diet, whereas expression of CD62 and spontaneous platelet aggregation were slightly higher after the olive oil diet. However, given the major differences in the fatty acid compositions of the diets, the differences between the groups with respect to hemostasis tended to be small. Therefore, the clinical significance of the present findings remains to be evaluated.
Vitamin E and Cardiovascular Disease
Authors: Marchioli Roberto 
Published: March 2018

SummaryInterest in the use of antioxidants for the treatment of human disease, and in the role of dietary antioxidants in the prevention of disease development, has been sustained for at least two decades. Several anti-oxidant protective mechanisms exist and constitute a primary defensive system including enzymatic defences (glutathione peroxidase and superoxide dismutase, which depend on the presence of ions such as selenium, zinc, copper, and manganese) and naturally occurring vita-mins such as vitamin E, vitamin A, beta-carotene, and vitamin C. The most important natural antioxidants are vitamin E (in the form of α-, β-, γ-, and δ-tocopherols), beta-carotene, vitamin C and selenium (fundamental constituent of glutathione-peroxidase, i.e., an enzyme with antioxidant function). The first two are lipophilic substances whilst ascorbic acid is hydrophilic. Each antioxidant has a different important mechanism of action since oxidative damage can be caused by lipid- or water-soluble molecules. Lipid-soluble antioxidants are likely to be very important in preventing the peroxidation of low-density lipo-proteins (LDL) and this action could be paramount in the prevention of atherosclerosis. On the other hand, water-soluble antioxidants could be useful where a water-soluble oxidative stress occurs (e.g., inflammation). As lipophilic molecules, vitamin E and beta-carotene are incorporated into the LDL particle. Vitamin E is the main lipid-soluble chain-breaking antioxidant in plasma and tissues and converts the peroxyl-free radical to hydroperoxide, a less reactive radical. It acts as a first-line anti-oxidative defence of LDL particles, protecting unsatu-rated fatty acids from peroxidation. Beta-carotene is a carotenoid (precursor of vitamin A, pro-vitamin) that acts as scavenger of oxidising radicals such as singlet oxygen and is a second-line antioxidative defence of LDL cholesterol. Vitamin C (ascorbic acid) can react with singlet oxygen, superoxide, hydroxyl radicals, and is the first line of antioxi-dative defence in water-soluble compartments. In addition, it plays an important role in regenerating reduced -tocopherol.
Prospective Study on the Usefulness of Lung Scan in Patients with Deep Vein Thrombosis of the Lower Limbs
Authors: Ruiz Joan , Fraile Manuel , Bonet Montserrat , Davant Ester , Muchart Jordi , Vallejos Virginia , Monreal Manuel 
Published: March 2018

Summary
Background: Asymptomatic pulmonary embolism (PE) is a common finding in patients with deep venous thrombosis (DVT) of the lower limbs, but the usefulness of seeking for silent PE in patients with acute DVT has not been evaluated. Patients and methods: This was a prospective study involving consecutive patients with acute symptomatic proximal DVT (confirmed by objective methods) and no clinical suspicion of PE. All patients underwent chest X-ray, ventilation-perfusion lung scan and arterial blood gases on admission, and received anticoagulant therapy. Those with scintigraphic evidence of PE underwent repeated lung scan and blood gases 7 days later. The aim of the study was to assess how many patients with silent PE develop symptoms while on heparin therapy, and in how many of them such symptoms are due to recurrent PE. Results: 946 consecutive patients with acute, proximal DVT had no contraindications to full-dose anticoagulant therapy. Baseline lung scan revealed high-probability defects (silent PE) in 200 (21%). Seven of these 200 patients had symptomatic recurrences during the 7-day study period, and an inferior vena cava filter was inserted. Besides, 6 patients developed PE symptoms, but no new perfusion defects were found on repeated scan. They switched to coumarin therapy, and they did not develop any further complications. Conclusions: Lung scan in patients with symptomatic DVT and no clinical suspicion of PE may be useful, since some patients with silent PE may develop symptoms while on heparin therapy. Without a baseline scintigraphy all these patients would have been considered to have recurrent PE, and vena cava interruption could have been performed.
SR123781A, a Synthetic Heparin Mimetic
Authors: Hérault J. P. , Bernat A. , Savi P. , Schaeffer P. , Driguez P. A. , Duchaussoy Ph. , Petitou M. , Herbert J. M. 
Published: March 2018

SummarySR123781A, a synthetic hexadecasaccharide comprising an anti-thrombin (AT) binding domain, a thrombin binding domain, and a neutral methylated hexasaccharide sequence, was obtained from glucose through a convergent synthesis. SR123781A showed high affinity for human AT (Kd = 58 ± 22 nM) and was a potent catalyst of its inhibitory effect with regard to factor Xa (IC50 = 77 ± 5 ng/ml – 297 ± 13 U/mg) and thrombin (IC50 = 4.0 ± 0.5 ng/ml – 150 ± 30 U/mg). SR123781A which acted exclusively via AT (no effect via heparin cofactor II at a concentration of 6 g/ml) inhibited thrombin generation occurring via both the extrinsic and intrinsic pathways in vitro in human plasma. SR123781A did not compete for 3H-heparin binding to PF4 and did not activate platelets in the presence of plasma from patients with heparin-induced thrombocytopenia. After intravenous or subcutaneous administration to rats, rabbits or baboons, SR123781A displayed prolonged anti-factor Xa and anti-factor IIa activity ex vivo. After intravenous injection to baboons, decreases of the anti-factor Xa and anti-thrombin activities were parallel and disappeared with the same pharmacodynamics. Intravenous administrations of SR123781A strongly inhibited thrombus formation in an experimental model of thromboplastin-induced venous thrombosis in rats with an ED50 value of 18 ± 0.1 g/kg (vs 77 ± 3 g/kg for heparin). SR123781A inhibited arterial thrombus formation induced on a silk thread in an arterio-venous shunt and in the vena cava (ED50 values of 225 ± 10 and 27 ± 8 g/kg, respectively). Compared to standard and low molecular weight heparin and to presently used drugs, SR123781A exhibited a highly favourable anti-thrombotic/bleeding ratio therefore showing that it might be considered as a promising compound in the treatment and prevention of various thrombotic diseases.
Histidine-Proline-Rich Glycoprotein Binding to Platelets Mediated by Transition Metals
Authors: Merryman Paula , Cullinane Ann , Horne McDonald 
Published: March 2018

SummaryHistidine-proline-rich glycoprotein (HPRG) binds zinc, which in turn promotes HPRG binding to lymphocytes and monocytes. We examined the possibility that zinc and other transition metals also promote HPRG binding to platelets. Only non-specific, unsaturable association of HPRG with resting or activated platelets was observed in the absence of transition metals. However, nickel, cobalt, copper, cadmium, and zinc greatly increased HPRG association with the cells. In the presence of zinc, specific, saturable binding of HPRG to platelets was demonstrated. The cell binding capacity for HPRG could be increased by increasing the zinc saturation of HPRG from 10% to 30% as well as by activating the platelets with thrombin. Because platelets contain relatively high concentrations of secretable zinc, it is possible that significant amounts of HPRG bind to activated platelets at sites of blood clotting and that this has a physiologic function.
Localization of β2-Glycoprotein 1 in Late Endosomes of Human Endothelial Cells
Authors: Dunoyer-Geindre S. , Kruithof E. K. O. , Rochemonteix Galve-de , Rosnoblet C. , Gruenberg J. , Reber G. , de Moerloose P. 
Published: March 2018

SummaryAntiphospholipid antibodies (APLA) are associated with thrombophilia and recurrent pregnancy loss. Different mechanisms have been proposed to explain their pathogenic effects and among them, we have previously shown that APLA accumulate in late endosomes of human umbilical vein endothelial cells (HUVEC) leading to a redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR). Because many APLA are directed towards β2-glycoprotein 1 (β2GP1)-phospholipid complexes, we investigated the localisation of β2GP1 in HUVEC. By immunofluorescence analysis, using monoclonal and polyclonal anti- β2GP1 antibodies, we detected β2GP1 at the cell surface and in late endosomes. Incubation of HUVEC with anti- β2GP1 antibodies resulted in antibody accumulation at the cell surface and within late endosomes and in a redistribution of the CI-M6PR from the Golgi apparatus to late endosomes. The anti- β2GP1 antibodies remained detectable in late endosomes even after several days of incubation in antibody-free medium. The accumulation of anti- β2GP1 antibodies in late endosomes of endothelial cells and the resulting modification of intracellular protein trafficking may contribute to the pathogenic effects of these antibodies.
Hautbefunde bei Kindesmisshandlung aus rechtsmedizinischer Sicht
Authors: Mützel E. , Adamowicz S. 
Published: March 2018

ZusammenfassungKindesmisshandlung ist kein seltenes Phänomen. Jeder Arzt kann mit Misshandlungsopfern konfrontiert werden. Als Grenzfläche zur Außenwelt und als unser größtes Organ ist die Haut bei Kindesmisshandlungen am häufigsten betroffen und gleichzeitig ist sie auch das dem Auge zugänglichste Organ. Erkennen misshandlungsverdächtiger Hautbefunde sowie deren Abgrenzung zu unfallbedingten Verletzungen und Hauterkrankungen können in der Praxis jedoch oft schwierig sein, eine interdisziplinäre Zusammenarbeit ist häufig erforderlich. Durch Gewaltopferambulanzen und telemedizinische Portale ist auch die klinische Rechtsmedizin in den letzten Jahren zunehmend tätig geworden. Dieser Artikel soll die häufigsten dermatologischen Manifestationen der Kindesmisshandlung aufzeigen sowie Kriterien zur Abgrenzung gegenüber unfallbedingten Hautverletzungen und differenzialdiagnostisch wichtigen Hauterkrankungen aus rechtsmedizinischer Sicht kurz diskutieren.
Neue Medien, neue Störungen?
Authors: Wolf R. C. , Wolf N. D. 
Published: March 2018

Zusammenfassung
Gegenstand und Ziel: Anhand eines Fallberichts soll auf klinisch relevante Auswirkungen dysfunktionaler Smartphone-App-Nutzung aufmerksam gemacht werden. Material und Methoden: Der Fallbericht stützt sich auf Anamnese und klinische Befunderhebung im Verlauf einer tagesklinischen Behandlung eines Patienten mit dysfunktionaler Smartphone-App-Nutzung. Nach einer selektiven Recherche wurden rezente Publikationen zur dysfunktionalen Smartphonenutzung berücksichtigt. Ergebnisse: Durch die tagesklinische Behandlung konnte insgesamt ein deutlicher Rückgang (vor allem eine zeitliche Reduktion) pathologischen Nutzerverhaltens erreicht werden. In der wissenschaftlichen Literatur zeichnet sich ein wachsendes Interesse an störungsrelevanter Dysfunktionalität im Zusammenhang mit dem Gebrauch von Smartphones und der Nutzung von Smartphone-Apps ab. Schlussfolgerung/klinische Relevanz: Kommunikationswirksame Smartphone-Apps bergen das Risiko exzessiven und dysfunktionalen Verhaltens. Es ist möglich, dass mit der zunehmenden Popularität dieser Kommunikationsmedien pathologisches Nutzverhalten zunehmend auch behandlungsrelevant wird. Ob aus diesen „neuen Störungen“ auch neue Diagnosen abgeleitet werden könnten, ist noch ungewiss. In Zukunft dürften insbesondere präventive Aspekte bedeutsam werden.
Foetal Growth Restriction in Children with Prothrombotic Risk Factors
Authors: Kries Rüdiger von , Junker Ralf , Oberle Doris , Kosch Andrea , Nowak-Göttl Ulrike 
Published: March 2018

SummaryPlacental infarction is frequently observed in low birth weight children. To evaluate whether low birth weight in healthy term neonates is associated with foetal inherited prothrombotic risk factors this retrospective study was conducted. Outcome measures were “birth weight in the lowest quartile” and “birth weight in the lowest decile” in singletons with a gestational age of ≥37 weeks.The analyses were based on 375 Caucasian children screened at the Münster childhood thrombophilia centre with complete data for all prothrombotic risk factors (factor V G1691A, prothrombin G20210A, elevated lipoprotein (a), protein C-, protein S-, antithrombin-deficiency). The proportion of children in the lowest birth weight quartile increased from 23.7% to 30.5% to 48.0% for children with no, only single heterozygous and multiple or homozygous defects respectively. The respective adjusted odds ratios (95% confidence intervals) of thrombophilia for birth weight in the lowest quartile (lowest decile) were 1.53 (0.76-3.08) in carriers of one prothrombotic risk factor and 4.01 (1.48-10.84) in subjects carrying multiple or homozygous defects. We identified foetal thrombophilia as an additional cause of low birth weight.
Extracellular Signal-regulated Kinase (ERK) Activation Is Required for GP Ibα-dependent Endothelial Cell Migration
Authors: Lian Jie , Marcinkiewicz Cezary , Niewiarowski Stefan , Beacham Dorothy 
Published: March 2018

SummaryThe GP Ib complex can participate in endothelial cell (EC) migration on von Willebrand factor (vWF) or the mixed matrix of vWF and type I collagen (vWF/collagen). In this study, viper venom proteins alboaggregin (albo) A or B blocked GP Ibα, and echistatin inhibited αvβ3 binding. Albo A, B and echistatin inhibited EC migration on vWF and vWF/collagen. Albo B or the anti-GP Ibα monoclonal antibody (mAb) 1b1 did not affect the migration of smooth muscle cells or fibroblasts, which lack GP Ib. EC also migrate on albo A- or albo B-coated dishes. PD98059, which blocks ERK activation, abolished EC migration on vWF, vWF/collagen, collagen or albo B. Soluble albo A or 1b1 dramatically inhibited ERK activation during EC migration on vWF or albo B. Echistatin inhibited ERK activation on vWF and vitronectin (VN), but not albo B. Thus, in addition to αvβ3, EC GP Ibα initiates ERK activation, and regulates ERK-induced EC migration on vWF.
Recombinant Tissue Factor Pathway Inhibitor Prevents Lipopolysaccharide-induced Systemic Hypotension in Rats by Inhibiting Excessive Production of Nitric Oxide
Authors: Enkhbaatar Perenlei , Uchiba Mitsuhiro , Isobe Hirotaka , Okabe Hiroaki , Okajima Kenji 
Published: March 2018

SummaryExcessive production of nitric oxide (NO) by the inducible form of NO synthase (iNOS) plays a key role in the development of endotoxin shock. Tumor necrosis factor-α (TNF-α) induces iNOS, thereby contributing to the development of shock. We recently reported that recombinant tissue factor pathway inhibitor (r-TFPI), an important inhibitor of the extrinsic pathway of the coagulation system, inhibits TNF-α production by monocytes. In this study, we investigated whether r-TFPI could ameliorate hypotension by inhibiting excessive production of NO in rats given lipopolysaccharide (LPS). Pretreatment of animals with r-TFPI prevented LPS-induced hypotension. Recombinant TFPI significantly inhibited the increases in both the plasma levels of NO2
-/NO3
- and lung iNOS activity 3 h after LPS administration. Expression of iNOS mRNA in the lung was also inhibited by intravenous administration of r-TFPI. However, neither DX-9065a, a selective inhibitor of factor Xa, nor an inactive derivative of factor VIIa (DEGR-F.VIIa) that selectively inhibits factor VIIa activity, had any effect on LPS-induced hypotension despite their potent anticoagulant effects. Moreover, neither the plasma levels of NO2
-/NO3
- nor lung iNOS activity were affected by administration of DX-9065a and DEGR-F.VIIa. These results suggested that r-TFPI ameliorates LPS-induced hypotension by reducing excessive production of NO in rats given LPS and this effect was not attributable to its anticoagulant effects, but to the inhibition of TNF-α production.
Hereditärer Faktor-V-Mangel und Faktor- V-Inhibitor ohne Blutungsneigung
Authors: Töpfer G. , Hartung K.-J. , Lutze G. , Borucki K. 
Published: March 2018

ZusammenfassungIsolierte Verminderungen der Faktor-V-Aktivität werden als angeborener Faktor-V- Defekt bei der Hypoproakzelerinämie und als erworbener Zustand bei Inhibitoren, die gegen Faktor V gerichtet sind, beobachtet. Eine Blutungssymptomatik kann bei beiden Ursachen vorhanden sein oder fehlen. Untersucht wurden zwei Patienten ohne Blutungssymptomatik, die durch pathologische Globaltests auffällig wurden. Ein angeborener und ein erworbener Faktor- V-Mangel wurden nachgewiesen.