In vivo assessment of the effects of ginsenoside Rb1 on intimal hyperplasia in ApoE knockout mice.

OBJECTIVE: This study investigated the effects of ginsenoside Rb1 (Rb1) on injury-induced intimal hyperplasia in ApoE knock out (ApoE -/-) mice. We also examined the value of an ultrasound micro-image system in dynamic monitoring of lumen diameter and flow velocity. METHODS: After guide wire injury of the distal left common carotid artery (CCA), ApoE-/- mice were treated with intraperitoneal infusion of normal saline (NS), homocysteine (Hcy), ginsenoside Rb1 (Rb1), or Hcy+Rb1 for 4 wk. Bilateral CCA luminal diameters and flow velocities were measured with an ultrasound micro-image system before surgery and weekly afterwards. Following the final ultrasound, CCAs were harvested and analyzed for intima-medium thickness ratios. RESULTS: Progressive reduction in luminal diameters and increase in flow velocity of the injured left distal CCA segment were observed using ultrasound micro-imaging system in all groups compared with the relatively stable left proximal CCA and right CCA. The NS and Hcy groups had significantly higher degree of diameter reduction compared with the Rb1 and Rb1+Hcy groups. The ultrasound findings were consistent with histology analyses at 4 wk post-op. CONCLUSIONS: The study suggested that Rb1 attenuated the effects of Hcy on injured carotid arteries of ApoE -/- mice. The study also showed that ultrasound micro-image system was a reliable tool in monitoring luminal reduction after injury in a murine model. This study establishes a fundamental step of in vivo monitoring of the therapeutic effects of agents in a murine model without sacrificing the animals.

Using the stochastic collocation method for the uncertainty quantification of drug concentration due to depot shape variability.

Numerical simulations entail modeling assumptions that impact outcomes. Therefore, characterizing, in a probabilistic sense, the relationship between the variability of model selection and the variability of outcomes is important. Under certain assumptions, the stochastic collocation method offers a computationally feasible alternative to traditional Monte Carlo approaches for assessing the impact of model and parameter variability. We propose a framework that combines component shape parameterization with the stochastic collocation method to study the effect of drug depot shape variability on the outcome of drug diffusion simulations in a porcine model. We use realistic geometries segmented from MR images and employ level-set techniques to create two alternative univariate shape parameterizations. We demonstrate that once the underlying stochastic process is characterized, quantification of the introduced variability is quite straightforward and provides an important step in the validation and verification process.

Angiographic and 3D intravascular ultrasound assessment of overlapping bare metal stent and three different formulations of drug-eluting stents in patients with diabetes mellitus.

OBJECTIVES: The aim of this study was to examine the impact of overlapping bare-metal stent (BMS) and three different formulations of drug-eluting stent (DES) on intimal hyperplasia (IH) response of patients with diabetes mellitus (DM). METHODS: Forty-nine DM patients treated with overlapping BMS (19 lesions), sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8 lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and 9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) analysis were performed in the entire stented segment and in the overlapped (OL) and non-overlapped (non-OL) subsegments. Clinical outcomes were evaluated at 1-year follow-up. RESULTS: Post-procedure (PO-) QCA measurements were similar in all stent groups, and between OL and non-OL subsegments in each individual type of stents. Percent IH was lower in SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type of DES groups. SES showed significantly less %IH compared with PES and TES in OL and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in all type of DES and BMS groups. There were no aneurysm formation and no stent thrombosis up to 1-year follow-up. CONCLUSIONS: Overlapping BMS is associated with enhanced IH response in diabetic patients, whereas overlapping DES, particularly SES and PES, appear effective to inhibit IH without detectable late vascular adverse effects.

Hemodialysis access failure: a call to action.

Recent evidence suggests that the cost as well as the morbidity associated with the maintenance of hemodialysis access is increasing rapidly; currently, the cost exceeds 1 billion dollars and access related hospitalization accounts for 25% of all hospital admissions in the U.S.A. This increase in cost and morbidity has been associated with several epidemiological trends that may contribute to access failure. These include late patient referral to nephrologists and surgeons, late planning of vascular access as well as a shift from A-V fistulaes to PTFE grafts and temporary catheters, which have a higher failure rate. The reasons for this shift in the types of access is multifactorial and is not explained by changes in the co-morbidities of patients presenting to dialysis. Surgical preference and training also appear to play an important role in the large regional variation and patency rate of these PTFE grafts. We propose a program for early placement of A-V fistulae, a continuous quality improvement, multidisciplinary program to monitor access outcome, the development of new biomaterials, and a research plan to investigate pharmacological intervention to reduce development of stenosis and clinical interventions to treat those that do develop, prior to thrombosis.