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Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization. No significant benefit is seen with the use of a paclitaxel-containing contrast medium. (ClinicalTrials.gov number, NCT00156624 [ClinicalTrials.gov].).

Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as provide potential insight into the trafficking and entry mechanism of other filoviruses.

Ultrasound contrast agents (UCA), in conjunction with contrast specific imaging techniques, are increasingly accepted in clinical use for diagnostic imaging and post-interventional workup in several organs. Presently, there is no guidance document providing a description of essential technical requirements, proposed investigator qualifications, suggested investigational procedures and steps, guidance on image interpretation, recommended and established clinical indications and safety considerations.The need for these guidelines was highlighted following the EFSUMB Board of Directors (Delegates) meeting at the EUROSON Congress at Copenhagen in March, 2003. During their development these guidelines were presented at the EFSUMB special consensus meeting for the use of contrast agents in ultrasound

Human embryonic lung fibroblasts (LU) can be productively infected with human cytomegalovirus (HCMV). During the course of productive infection, the virus elicits a number of responses that resemble certain aspects of G1 cell cycle progression. The virus activates cyclin E/Cdk2 kinase in both subconfluent, serum-arrested, and density-arrested cultures. Activation of cyclin E-dependent kinase is due, in part, to induction of cyclin E and, in part, to inhibition of the cyclin kinase inhibitors, Cip1 and Kip1. However, G1 progression is incomplete in HCMV-infected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA synthesis does not occur if one takes care to avoid addition of fresh serum to serum-starved cultures. The data indicate that the virus induces a state of late G1 arrest, in which cyclin E/Cdk2 activates nucleotide metabolism and other biosynthetic processes that are necessary for viral replication. Failure to activate host cell DNA synthesis ensures that the virus will have uncompleted access to such precursors.

P ercutaneous revascularization is an established treatment for femoro-popliteal artery disease.1 Yet, restenosis, reocclusion, and ensuing symptom recurrence can occur in as many as 50% of patients undergoing percutaneous transluminal angioplasty (PTA), often requiring repeat percutaneous or surgical intervention.2,3 The superficial femoral artery represents a unique challenging vessel.4 Bare-metal stents reduce restenosis versus PTA and have gained widespread adoption. 5,6 Alternative therapies, such as drug-eluting balloon (DEB), may be valuable and worthwhile considering their promise and evidence to achieve patency outcomes at least similar to stents but with nothing left behind. 7Several studies in coronary artery disease indicate effective restenosis inhibition by DEB in the treatment of in-stent restenosis whereas drug-eluting stent are the preferred medicated devices in most coronary de novo lesions. Two published randomized trials have so far provided favorable data on the usage of DEB versus PTA for the treatment of femoropopliteal arterial disease. 8,9 More recently, the effect of a novel paclitaxel coating formulation with urea excipient, a naturally occurring highly biocompatible hydrophilic component (FreePac, Medtronic, Santa Rosa, CA) was investigated within a multicenter registry in patients affected by femoral-popliteal arterial disease. 10 To reach a more in-depth understanding onBackground-Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention.A drug-eluting balloon (DEB) based on a novel coating was compared with uncoated balloons in patients undergoing femoropopliteal percutaneous transluminal angioplasty. Methods and Results-Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminalangioplasty were randomized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons. The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses. Secondary end points were binary restenosis and Rutherford class change at 6 months, and target lesion revascularization plus major adverse clinical events (major adverse events=death, target limb amputation, or target lesion revascularization) at 6 and 12 months. Eighty-five patients (91 cases=interventional procedures) were randomized in 3 hospitals (44 to DEB and 47 to uncoated balloons). Average lesion length was 7.0±5.3 and 6.6±5.5cm for DEB and control arm, respectively.

The association between human cytomegalovirus (HCMV) infection and glioblastoma has been a source of debate in recent years because of conflicting laboratory reports concerning the presence of the virus in glioma tissue. HCMV is a ubiquitous herpesvirus that exhibits tropism for glial cells and has been shown to transform cells in vitro. Using sensitive immunohistochemical and in situ hybridization methods in 50 glioma samples, we detected HCMV antigen and DNA in 21/21 cases of glioblastoma, 9/12 cases of anaplastic gliomas, and 14/17 cases of low-grade gliomas. Reactivity against the HCMV IE1 antigen (72 kDa) exhibited histology-specific patterns with more nuclear staining for anaplastic and low-grade gliomas, while GBMs showed nuclear and cytoplasmic staining that likely occurs with latent infection. Using IHC, the number of HCMVpositive cells in GBMs was 79% compared to 48% in lower grade tumors. Non-tumor areas of the tissue contained only 4 % and 1% of HCMV-positive cells for GBMs and lower grade tumors, respectively. Hybridization to HCMV DNA in infected cells corresponded to patterns of immunoreactivity. Our findings support previous reports of the presence of HCMV infection in glioma tissues and advocate optimization of laboratory methods for the detection of active HCMV infections. This will allow for detection of low-level latent infections that may play an important role in the initiation and/or promotion of malignant gliomas.