What is the optimal duration of treatment for DVT? An update on evidence-based medicine of treatment for DVT.

Venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism, represent a major source of morbidity and mortality today. Incidence of DVT is estimated to be 56 to 160/100,000 population per year. Systemic anticoagulation with low molecular weight heparin or unfractionated heparin with initiation of oral vitamin K antagonist therapy has been shown to be beneficial in preventing pulmonary embolism and reducing extension and recurrence of DVT. The duration of anticoagulation following an episode of DVT is determined by the greatest predictors of recurrence. These include the presence of reversible risk factors, nonreversible risk factors, and no risk factors (idiopathic or unprovoked DVT). Short durations of anticoagulation are only appropriate for calf DVTs in patients with reversible risk factors. Patients with nonreversible risk factors, such as malignancy and certain inherited thrombophilias with a strong family history of venous thromboembolism will require lifelong anticoagulation. Those with proximal DVT due to reversible risk factors require 3 to 6 months of anticoagulation. Patients with idiopathic DVT require reassessment of risk-to-benefit ratio of hemorrhage from oral vitamin K antagonist therapy compared to reducing risk of recurrence and frequently require prolonged oral anticoagulant therapy. Monitoring with d-dimer and serial ultrasounds may offer an individualized approach to therapy.

Molecular mediators of angiogenesis.

Angiogenesis, or the formation of new blood vessels from the preexisting vasculature, is a key component in numerous physiologic and pathologic responses and has broad impact in many medical and surgical specialties. In this review, we discuss the key cellular steps that lead to the neovascularization of tissues and highlight the main molecular mechanisms and mediators in this process. We include discussions on proteolytic enzymes, cell-matrix interactions, and pertinent cell signaling pathways and end with a survey of the mechanisms that lead to the stabilization and maturation of neovasculatures.

Characterization of the chemotactic and mitogenic response of SMCs to PDGF-BB and FGF-2 in fibrin hydrogels.

The delivery of growth factors to cellularize biocompatible scaffolds like fibrin is a commonly used strategy in tissue engineering. We characterized smooth muscle cells (SMC) proliferation and chemotaxis in response to PDGF-BB and FGF-2, alone and in combination, in 2D culture and in 3D fibrin hydrogels. While both growth factors induced an equipotent mitogenic response in 2D culture, only FGF-2 was significantly mitogenic for SMCs in 3D culture. Only PDGF-BB was significantly chemotactic in a modified Boyden chamber assay. In a 3D assay of matrix invasion, both growth factors induced an invasive response into the fibrin hydrogel in both proliferating and nonproliferating, mitomycin C (MMC) treated cells. The invasive response was less attenuated by the inhibition of proliferation in PDGF-BB stimulated cells compared with FGF-2 stimulated cells. We conclude that SMCs cultured in fibrin hydrogels have a more robust chemotactic response to PDGF-BB compared with FGF-2, and that the response to FGF-2 is more dependent on cell proliferation. Delivery of both growth factors together potentiates the chemotactic, but not mitogenic response to either growth factor alone.

Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement.

A target-specific MRI contrast agent for tumor cells expressing high affinity folate receptor was synthesized using generation five (G5) ofpolyamidoamine (PAMAM) dendrimer. Surface modified dendrimer was functionalized for targeting with folic acid (FA) and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III). Dendrimer-DOTA conjugates were then complexed with GdCl3 followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s(-1) mM(-1)) of water. In xenograft tumors established in immunodeficient (SCID) mice with KB human epithelial cancer cells expressing folate receptor (FAR), the 3D MRI results showed specific and statistically significant signal enhancement in tumors generated with targeted Gd(III)-DOTA-G5-FA compared with signal generated by non-targeted Gd(III)-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infiltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specific delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specificity of the dendrimer nanoparticles for targeted cancer imaging with the prolonged clearance time compared with the current clinically approved gadodiamide (Omniscan) contrast agent. Potential application of this approach may include determination of the folate receptor status of tumors and monitoring of drug therapy.