Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study tests the feasibility of inhalable pegylated liposomal formulations of low molecular weight heparin (LMWH) for treatment of two clinical manifestations of vascular thromboembolism: deep vein thrombosis (DVT) and pulmonary embolism (PE). Conventional distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and long-circulating pegylated (DSPE-PEG-2000 and DSPE-PEG-5000) liposomes were prepared by hydration method. Formulations were evaluated for particle size, entrapment efficiency, stability, pulmonary absorption, anticoagulant, and thrombolytic effects in rats. Pulmonary absorption was monitored by measuring plasma antifactor Xa activity; anticoagulant and thrombolytic effects were studied by measuring reduction in thrombus weight and amount of dissolved radioactive clot in the blood, respectively. Pegylated liposomal were smaller and showed greater drug entrapment efficiency than conventional liposomes. All formulations produced an increase in pulmonary absorption and circulation time of LMWH upon first dosing. Three repeated dosings of conventional liposomes resulted in decreased half-life and bioavailability; no changes in these parameters were observed with pegylated liposomes. PEG-2000 liposomes were effective in reducing thrombus weight when administered every 48 h over 8 days. In terms of thrombolytic effects and dosing frequency, PEG-2000 liposomes administered via the pulmonary route at a dose of 100 U/kg were as effective as 50 U/kg LMWH administered subcutaneously. This paper suggests that inhalable pegylated liposomes of LMWH could be a potential noninvasive approach for DVT and PE treatment.
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PMID:Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolism. 2084 54

DMP444 is a (99m)Tc-labeled cyclic RGD peptide, which has been evaluated in preclinical canine deep vein thrombosis (DVT) and pulmonary embolism (PE) models, and in patients with DVT and PE by SPECT (single photon emission computed tomography). Clinical data indicated that DMP444 is useful for imaging DVT, but it had limited utility for imaging PE in patients. To understand its clinical findings, we prepared a new radiotracer P4-DMP444 by replacing the lipophilic 6-aminocaproic acid (CA) in DMP444 with a highly water-soluble PEG(4) (15-amino-4,7,10,13-tetraoxapentadecanoic acid) linker. The objective of this study was to explore the impact of PEG(4) on biological properties (biodistribution, excretion kinetics, and capability to image thrombi) of (99m)Tc radiotracer. We also used canine DVT and PE models to perform imaging studies with/without the heparin pretreatment. These studies were specifically designed to explore the impact of heparin treatment on thrombosis uptake of P4-DMP444. It was found that replacing the CA linker with PEG(4) could enhance the radiotracer clearance kinetics from blood and normal organs in both rats and dogs. The fact that P4-DMP444 and DMP444 share very similar thrombosis uptake in both DVT and PE models suggests that the PEG(4) linker has little effect on GPIIb/IIIa binding affinity of cyclic RGD peptide. Even though P4-DMP444 had less accumulation than DMP444 in the blood, heart, lungs, and muscle over the 2 h study period in both rats and dogs, the difference in PE/lung and DVT/muscle ratios is marginal, suggesting that one PEG(4) linker is not sufficient to dramatically change the contrast between thrombus and background. It is very important to note that the heparin treatment of dogs with DVT and PE resulted in dramatic decrease in accumulation of P4-DMP444 in fresh thrombi. On the basis of these results, we believe that DMP444 and P4-DMP444 are excellent radiotracers for imaging both DVT and PE, and should be used in patients without antithrombosis treatment at the time of imaging.
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PMID:Evaluation of 99mTc-labeled cyclic RGD peptide with a PEG4 linker for thrombosis imaging: comparison with DMP444. 2178 Aug 18

The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents.
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PMID:In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents. 2403 99