Fibrin-specificity of a plasminogen activator affects the efficiency of fibrinolysis and responsiveness to ultrasound: comparison of nine plasminogen activators in vitro

In a number of cases, thrombolytic therapy fails to re-open occluded blood vessels, possibly due to the occurrence of thrombi resistant to lysis. We investigated in vitro how the lysis of hardly lysable model thrombi depends on the choice of the plasminogen activator (PA) and is accelerated by ultrasonic irradiation. Lysis of compacted crosslinked human plasma clots was measured after addition of nine different PAs to the surrounding plasma and the effect of 3 MHz ultrasound on the speed of lysis was assessed. Fibrin-specific PAs showed bell-shaped dose-response curves of varying width and height. PAs with improved fibrin-specificity (staphylokinase, the TNK variant of tissue-type PA [tPA], and the PA from the saliva of the Desmodus rotundus bat) induced rapid lysis in concentration ranges (80-, 260-, and 3,500-fold ranges, respectively) much wider than that for tPA (a 35-fold range). However, in terms of speed of lysis, these three PAs exceeded tPA only slightly. Reteplase and single-chain urokinase were comparable to tPA, whereas two-chain urokinase, anistreplase, and streptokinase were inferior to tPA. In the case of fibrin-specific PAs, ultrasonic treatment accelerated lysis about 1.5-fold. For streptokinase no acceleration was observed. The effect of ultrasound correlated with the presence of plasminogen in the outer plasma, suggesting that it was mediated by facilitating the transport of plasminogen to the surface of the clot. In conclusion, PAs with improved fibrin-specificity induce rapid lysis of plasminogen-poor compacted plasma clots in much wider concentration ranges than tPA. This offers a possibility of using single-or double-bolus administration regimens for such PAs. However, it is not likely that administration of these PAs will directly cause a dramatic increase in the rate of re-opening of the occluded arteries since they are only moderately superior to tPA in terms of maximal speed of lysis. Application of high-frequency ultrasound as an adjunct to thrombolytic therapy may increase the treatment efficiency, particularly in conjunction with fibrin-specific PAs.     

Epidermal growth factor-induced cell rounding is sensitive to simulated microgravity

Epidermal growth factor (EGF) induces rapid rounding of A431 human epidermoid carcinoma cells. This process is dependent upon temperature and EGF concentration. To investigate the possible influence of gravity variations on EGF-induced cell rounding of A431 cells, experiments were performed using a fast-rotating clinostat and centrifuge, thereby simulating microgravity and higher gravity values, respectively. We demonstrated that simulated microgravity conditions enhance EGF-induced cell rounding significantly, whereas hypergravity values do not show significant effects on this process. These results suggest that simulated microgravity modulates growth factor-induced signal transduction.     

Emboli rate during and early after carotid endarterectomy after a single preoperative dose of 120 mg acetylsalicylic acid--a prospective double-blind placebo controlled randomised trial.

PURPOSE: To investigate whether a single pre-operative dose of 120 mg acetylsalicylic acid (ASA) decreased either (1) emboli rate, as detected by transcranial Doppler (TCD), during and early after carotid endarterectomy (CEA) and (2) clinical intra- and post-operative signs suggestive of embolism or increased bleeding tendency. DESIGN: Prospective, double-blind placebo controlled trial. PATIENTS AND METHODS: One-hundred consecutive patients were randomised to receive either 120 mg ASA (n = 48) or placebo (n = 49) by suppository on the night before CEA; three patients were excluded. Emboli were counted and expressed as emboli rate (ER). The incidence of bleeding complications was assessed. Surgeons were asked to indicate which patients had received ASA or placebo. RESULTS: There were no significant differences between the ASA and placebo groups in ER in the intraoperative and postoperative periods. ER higher than 0.9 min(-1) was associated with a significantly increased risk of complications (26 vs. 0%, P < 0.01). No extra bleeding complications were observed in the ASA group. Surgeon assessment of whether or not ASA had been administered had a sensitivity of 42% and a specificity of 70%. CONCLUSION: A single pre-operative dose of ASA (120 mg) did not reduce significantly the emboli rate during and after CEA and surgeons could not correctly identify whether or not ASA had been administered.     

Synchronous peritoneal metastases from lung cancer: incidence,associated factors,treatment and survival: a Dutch population-based study

Clinical & Experimental Metastasis - Peritoneal metastases (PM) from lung cancer are rare and it is unknown how they affect the prognosis of patients with lung cancer. This population-based...     

Matrix production and remodeling capacity of cardiomyocyte progenitor cells during in vitro differentiation

Cell-based therapy has emerged as a treatment modality for myocardial repair. Especially cardiac resident stem cells are considered a potential cell source since they are able to differentiate into cardiomyocytes and have improved heart function after injury in a preclinical model for myocardial infarction. To avoid or repair myocardial damage it is important not only to replace the lost cardiomyocytes, but also to remodel and replace the scar tissue by "healthy" extracellular matrix (ECM). Interestingly, the role of cardiac stem cells in this facet of cardiac repair is largely unknown. Therefore, we investigated the expression and production of ECM proteins, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in human cardiomyocyte progenitor cells (CMPCs) undergoing differentiation towards the cardiomyogenic lineage. Our data suggest that CMPCs have the capacity to synthesize and modulate their own matrix environment, especially during differentiation towards the cardiomyogenic lineage. While undifferentiated CMPCs expressed collagen I, III, IV and fibronectin, but no elastin, during the process of differentiation the expression of collagen I, III, IV and fibronectin increased and interestingly also elastin expression was induced. Furthermore, undifferentiated CMPCs express MMP-1 -2 and -9 and upon differentiation the expression of MMP-1 decreased, while the expression of MMP-2 and MMP-9, although the latter only in the early stage of differentiation, increased. Additionally, the expression of TIMP-1, -2 and -4 was induced during differentiation. This study provides new insights into the matrix production and remodeling capacity of human CMPCs, with potential beneficial effects for the treatment of cardiac injury.     

No Association of Phenotypic ABO Blood Group and Malaria during Pregnancy

Abstract. In a few small studies an association between blood group O and placental malaria has been described. The relationship between blood group and malaria in pregnancy (Plasmodium vivax and Plasmodium falciparum) was analyzed in 1,468 women from three longitudinal cohort studies in which weekly malaria screening was done systematically during pregnancy. One-third of women (447 of 1,468) had at least one malaria infection in pregnancy. The ABO blood group phenotype was not associated with the species of infection, frequency of malaria attacks, symptoms of malaria, hematocrit, or parasitemia during pregnancy.     

The effect of bed rest and an exercise countermeasure on leg venous function

This study was performed to assess the effect of resistive vibration exercise during bed rest deconditioning on venous vascular dimension and function, as measured with ultrasound in the popliteal vein. Sixteen men were assigned to bed rest (BR-Ctrl) or bed rest with resistive vibration exercise (BR-RVE). Before and at 25 and 52 days of bed rest, popliteal vein diameter was measured at increasing cuff pressures. Venous capacitance and compliance were calculated from the pressure–volume curve. After 52 days of bed rest, BR-Ctrl showed no change in baseline popliteal vein diameter or compliance, while venous capacitance decreased. Resistive vibration exercise had no effect on the response in venous diameter, capacitance or compliance to 52 days of bed rest. The decline in venous capacitance due to long-term bed rest is not effectively counteracted by resistive vibration exercise, indicating that an alternative factor during bed rest deconditioning is responsible for venous changes.