Glucose depletion of erythrocytes triggers suicidal erythrocyte death or eryptosis, which leads to cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptotic erythrocytes adhere to endothelial cells by a mechanism involving phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 at the endothelial cell membrane. Nothing has hitherto been known about an interaction between eryptotic erythrocytes and platelets, the decisive cells in primary hemostasis and major players in thrombotic vascular occlusion. The present study thus explored whether and how glucose-depleted erythrocytes adhere to platelets. To this end, adhesion of phosphatidylserine-exposing erythrocytes to platelets under flow conditions was examined in a flow chamber model at arterial shear rates. Platelets were immobilized on collagen and further stimulated with adenosine diphosphate (ADP, 10 μM) or thrombin (0.1 U/ml). As a result, a 48-h glucose depletion triggered phosphatidylserine translocation to the erythrocyte surface and augmented the adhesion of erythrocytes to immobilized platelets, an effect significantly increased upon platelet stimulation. Adherence of erythrocytes to platelets was blunted by coating of erythrocytic phosphatidylserine with annexin V or by neutralization of platelet phosphatidylserine receptors CXCL16 and CD36 with respective antibodies. In conclusion, glucose-depleted erythrocytes adhere to platelets. The adhesive properties of platelets are augmented by platelet activation. Erythrocyte adhesion to immobilized platelets requires phosphatidylserine at the erythrocyte surface and CXCL16 as well as CD36 expression on platelets. Thus platelet-mediated erythrocyte adhesion may foster thromboocclusive complications in diseases with stimulated phosphatidylserine exposure of erythrocytes.
Longitudinal data on the E6/E7 mRNA-based Aptima human papillomavirus (AHPV) assay exceeding three years in comparison to the gold standard Digene Hybrid Capture 2 (HC2) test are not available. We previously reported the cross-sectional data of the German AHPV Screening Trial (GAST) in which 10,040 women were recruited and tested by liquid-based cytology, the HC2 assay, and the AHPV assay.
(1) Background: Cervical intraepithelial neoplasia (CIN) of long-term persistence or associated with individual treatment indications often requires highly invasive treatments. These are associated with risks of bleeding, infertility, and pregnancy complications. For low- and middle-income countries (LMICs), standard treatment procedures are difficult to implement and manage. We characterized the application of the highly energized gas “noninvasive physical plasma” (NIPP) for tissue devitalization and the treatment of CIN. (2) Methods: We report the establishment of a promising tissue devitalization procedure by NIPP application. The procedure was characterized at the in vitro, ex vivo and in vivo levels. We performed the first prospective, single-armed phase-IIb trial in 20 CIN1/2 patients (NCT03218436). (3) Results: NIPP-treated cervical cancer cells used as dysplastic in vitro model exhibited significant cell growth retardation due to DNA damage, cell cycle arrest and apoptosis. Ex vivo and in vivo tissue assessments showed a highly noninvasive and tissue-preserving treatment procedure which induces transmucosal tissue devitalization. Twenty participants were treated with NIPP and attended a 24-week follow-up. Treatment success was achieved in 19 (95%) participants without postinterventional complications other than mild to moderate discomfort during application. (4) Conclusions: The results from this study preliminarily suggest that NIPP could be used for an effective and tissue-preserving treatment for CIN without the disadvantages of standard treatments. However, randomized controlled trials must confirm the efficacy and noninferiority of NIPP compared to standard treatments.
Hintergrund: Offizielle Leitlinie, publiziert und koordiniert von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (OEGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG). Durch die Einführung laparoskopischer Operationen wurde die vaginale und abdominale Hysterektomie um 3 weitere Techniken ergänzt. Um die Indikationsfelder abzugrenzen, wurde die Leitlinie "Indikation und Methodik der Hysterektomie bei benignen Erkrankungen" initiiert. Organerhaltende Therapiealternativen wurden ebenfalls integriert. Methode: Die Leitlinie wurde durch ein repräsentatives Gremium von 26 Experten aus Deutschland, Österreich und der Schweiz unter strukturierter unabhängiger Moderation im Konsens erstellt. Die systematische Literatursuche und-bewertung zu Nutzen und Schaden der Therapiealternativen bei symptomatischem Uterus myomatosus, funktionellen Blutungsstörungen und Adenomyosis sowie ein Vergleich der Hysterektomieverfahren erfolgte bis 06/2014 in der Datenbank MEDLINE mit Fokus auf aggregierter Evidenz. Ergebnisse: Alle Formen der Hysterektomie sind in Studien mit einer hohen Zufriedenheit der Patientinnen verbunden. Der vaginalen Hysterektomie soll gegenüber der abdominellen, wenn möglich, der Vorzug gegeben werden. Ist die vaginale Hysterektomie nicht möglich, sollte die Möglichkeit einer laparoskopischen Hysterektomie geprüft werden. Die abdominale Hysterektomie sollte nur bei gesonderter Indikation durchgeführt werden. Für die organerhaltenden Alternativen wurde ebenfalls ein hoher Zufriedenheitsgrad festgestellt, allerdings können bei Belassen des Uterus Rezidive auftreten.
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