Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

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Acyl-Enzymes as Thrombolytic Agents in a Rabbit Model of Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657183 ◽

1982 ◽

Vol 47 (03) ◽

pp. 269-274 ◽

Cited By ~ 32

Author(s):

R A G Smith ◽

R J Dupe ◽

P D English ◽

J Green

Keyword(s):

Venous Thrombosis ◽

Active Site ◽

Fibrinolytic Activity ◽

Rabbit Model ◽

Fibrinolytic Agent ◽

Essential Nature ◽

Thrombolytic Agents

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.

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Catestatin prevents endothelial inflammation and promotes thrombus resolution in acute pulmonary embolism in mice

Bioscience Reports ◽

10.1042/bsr20192236 ◽

2019 ◽

Vol 39 (11) ◽

Cited By ~ 3

Author(s):

Hua Chen ◽

Dongxia Liu ◽

Lan Ge ◽

Tao Wang ◽

Zhenzhen Ma ◽

...

Keyword(s):

Pulmonary Embolism ◽

Acute Pulmonary Embolism ◽

Thrombus Formation ◽

Vascular Dysfunction ◽

In Vivo Model ◽

Protective Effects ◽

Inhibitory Peptide ◽

Endothelial Inflammation

AbstractCatestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

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0272 : Deep venous thrombosis in patients with acute pulmonary embolism

Archives of Cardiovascular Diseases Supplements ◽

10.1016/s1878-6480(16)30343-3 ◽

2016 ◽

Vol 8 (3) ◽

pp. 195

Author(s):

Mariame Abelhad ◽

Fatima Ezzahra Sabri ◽

Ichraq Nassiri ◽

Hayat Najih ◽

Laila Azzouzi ◽

...

Keyword(s):

Pulmonary Embolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Acute Pulmonary Embolism

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Relationship of Lower-extremity Deep Venous Thrombosis Density at CT Venography to Acute Pulmonary Embolism and the Risk of Postthrombotic Syndrome

Radiology ◽

10.1148/radiol.2019190358 ◽

2019 ◽

Vol 293 (3) ◽

pp. 687-694 ◽

Cited By ~ 1

Author(s):

Min-Jae Jeong ◽

Hyunwook Kwon ◽

Minsu Noh ◽

Gi-Young Ko ◽

Dong Il Gwon ◽

...

Keyword(s):

Pulmonary Embolism ◽

Lower Extremity ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Acute Pulmonary Embolism ◽

Postthrombotic Syndrome ◽

Ct Venography ◽

Relationship Of

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Inhibitors of Acetylcholinesterase Derived from 7-Methoxytacrine and Their Effects on the Choline Transporter CHT1

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000453256 ◽

2016 ◽

Vol 43 (1-2) ◽

pp. 45-58 ◽

Cited By ~ 4

Author(s):

Zdenka Kristofikova ◽

Jan Ricny ◽

Ondrej Soukup ◽

Jan Korabecny ◽

Eugenie Nepovimova ◽

...

Keyword(s):

Side Effects ◽

Amyloid Β ◽

Acetylcholinesterase Inhibitors ◽

Side Chain ◽

Choline Transporter ◽

Disease Therapy ◽

Cortical Membranes ◽

Derivatives Of

Background: Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. Methods: We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Results: Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. Conclusion: The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research.

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Percutaneous mechanical thrombectomy combined with catheter-directed thrombolysis in the treatment of acute pulmonary embolism and lower extremity deep venous thrombosis: A novel one-stop endovascular strategy

Journal of International Medical Research ◽

10.1177/0300060517729898 ◽

2017 ◽

Vol 46 (2) ◽

pp. 836-851 ◽

Cited By ~ 3

Author(s):

Bing Liu ◽

MingYuan Liu ◽

LiHong Yan ◽

JunWei Yan ◽

Jiang Wu ◽

...

Keyword(s):

Pulmonary Embolism ◽

Lower Extremity ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Success Rate ◽

Acute Pulmonary Embolism ◽

Mechanical Thrombectomy ◽

Iliac Vein ◽

Percutaneous Mechanical Thrombectomy ◽

Catheter Directed Thrombolysis

Objective This study was performed to evaluate the efficacy and feasibility of percutaneous mechanical thrombectomy (PMT) combined with catheter-directed thrombolysis (CDT) in patients with acute pulmonary embolism (APE) and lower extremity deep venous thrombosis (LEDVT). Methods In total, 20 consecutive patients with APE and LEDVT were prospectively selected for PMT combined with CDT. Mechanical thrombus fragmentation and aspiration using a pigtail rotation catheter followed by CDT was performed in each patient. Details regarding the patients’ clinical presentation and outcome, pulmonary status parameters (pulmonary arterial pressure, partial pressure of oxygen in arterial blood, Miller score, thigh and calf circumference, and shock index), and lower extremity parameters (thrombus-lysis grade and Villalta scale score) were recorded. Results All 20 patients’ clinical manifestations significantly improved. Both the clinical success rate and technical success rate were 100%. No major adverse events occurred during hospitalization. Four patients developed iliac vein compression syndrome and underwent stent implantation in the iliac vein. No pulmonary embolism recurred within 16.5±6.8 months of follow-up. Conclusions The combination of PMT and CDT is a safe and effective treatment for APE and LEDVT with good short- and intermediate-term clinical outcomes.

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