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.
Manganese‐based contrast agents (MnCAs) have emerged as suitable alternatives to gadolinium‐based contrast agents (GdCAs). However, due to their kinetic lability and laborious synthetic procedures, only a few MnCAs have found clinical MRI application. In this work, we have employed a highly innovative single‐pot template synthetic strategy to develop a MnCA, MnLMe, and studied the most important physicochemical properties in vitro. MnLMe displays optimized r1 relaxivities at both medium (20 and 64 MHz) and high magnetic fields (300 and 400 MHz) and an enhanced r1b=21.1 mM−1 s−1 (20 MHz, 298 K, pH 7.4) upon binding to BSA (Ka=4.2×103 M−1). In vivo studies show that MnLMe is cleared intact into the bladder through renal excretion and has a prolonged blood half‐life compared to the commercial GdCA Magnevist. MnLMe shows great promise as a novel MRI contrast agent.
Objective: Bilateral tubal ectopic pregnancies are rare; the reported incidence is only 1 in 200?000 pregnancies. Detecting bilateral tubal ectopic pregnancy is urgent because of the associated morbidity and mortality. The appropriate fertility-preserving surgery must also be considered, as preservation of both tubes is presumed to offer better fertility prospects. Case Report: A 39-year-old gravida 2, para 1 presented with vaginal bleeding at 8?+?4 weeks of gestation. An approximately 18?mm adnexal mass in the right fallopian tube was detected on ultrasound. Laparoscopy was performed because ectopic pregnancy was suspected. This suspicion was confirmed during laparoscopy; the right fallopian tube was found to contain a mass measuring 20?mm in the isthmic part. Ultrasound of the left fallopian tube also showed a mass in the ampullary region (diameter: 10?mm), also suspicious for ectopic pregnancy. Bilateral salpingotomy was performed laparoscopically. Pathological examination confirmed the diagnosis. Conclusions for Practice: Although ectopic tubal pregnancy is seen more often after assisted reproductive techniques, bilateral spontaneous ectopic pregnancies must also be considered in other cases. Laparoscopic surgery is effective to confirm the diagnosis and treat heterotopic pregnancies. Further studies will be needed to confirm whether unilateral or bilateral conservative fertility-preserving surgery is more appropriate.
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