Effect of suture properties on stability of middle cerebral artery occlusion evaluated by synchrotron radiation angiography.

BACKGROUND AND PURPOSE: The intraluminal suture technique for producing middle cerebral artery occlusion in rodents is the most commonly used method for modeling focal cerebral ischemia associated with clinical ischemic stroke. Synchrotron radiation angiography may provide a novel solution to directly monitor the success of middle cerebral artery occlusion. METHODS: Twenty adult Sprague-Dawley rats for middle cerebral artery occlusion models were prepared randomly with different suture head silicone coating. In vivo imaging was performed at beam line BL13W1, Shanghai Synchrotron Radiation Facility, Shanghai, China. RESULTS: Silicone-coated suture was superior to uncoated suture for producing consistent brain infarction. Additionally, silicone coating length was an important variable controlling the extent of the ischemic lesion: infarcts affected predominantly the caudate-putamen with large variability (<2 mm), both the cortex and caudate-putamen (2-3.3 mm), and most of the hemisphere, including the hypothalamus (>3.3 mm). CONCLUSIONS: Synchrotron radiation angiography provides a useful tool to observe hemodynamic changes after middle cerebral artery occlusion, and the physical properties of suture are critical to the success of the middle cerebral artery occlusion model.

Evaluation of two polymeric blends (EVA/PLA and EVA/PEG) as coating film materials for paclitaxel-eluting stent application.

The ethylene vinyl acetate copolymer (EVA)/Poly (lactic acid) (PLA) blend and EVA/Poly (ethylene glycol) (PEG) blend were applied as the drug carrier materials for a bi-layer drug-loaded stent coating film, which consisted of a paclitaxel (PTX)-loaded layer and a drug-free EVA layer. The changes of weight and appearance of the drug-free polymeric blend films with increasing time were examined by X-ray diffraction analysis (XRD), gel permeation chromatography (GPC) tests and scanning electronic microscopy (SEM), and the results showed the degradation of PLA and the leaching of PEG from the films. The effects of PLA, PEG and drug contents on in vitro drug release were investigated, and the results demonstrated that the addition of PLA promoted the drug release while the addition of PEG almost did not. Franz cells diffusion test results indicated that the bi-layer structure successfully endowed the stent coating with the release of drug in a unidirectional fashion. The release profiles of films incorporated PTX and the mechanical performance of the film could be customized by readily adjusting the contents of the blend components. Therefore, the polymeric blends could be useful drug carrier materials for drug-loaded stent coating capable of releasing drug in a highly tunable manner.

Therapeutic endoscopy of localized gastric varices: pretherapy screening and posttreatment evaluation with MDCT portography.

BACKGROUND: Gastric varices are a major cause of gastrointestinal bleeding in patients with portal hypertension. Whatever therapeutic method is used, hemodynamic changes in the portal systemic shunt should be assessed. In this study, we used multi-detector row CT portography as a screening and assessment tool. METHODS: A total of 85 patients with gastroscopy-confirmed gastroesophageal varices underwent multi-detector row CT portography. Patients through multi-detector row CT portography screening were recommended to therapeutic endoscopy. Multi-detector row CT portography was carried out in these patients one week before treatment and one month after treatment. The cross-sectional areas of the left gastric vein, main portal vein, superior mesenteric vein and splenic vein were measured by advanced vessel analysis software before and after treatment. Data was subjected to statistical test. RESULTS: Of the 85 patients who underwent multi-detector row CT portography screening, 17 had localized gastric varices with a solitary afferent vein and were recommended for therapeutic endoscopy. The changes in cross-sectional areas of the left gastric vein, main portal vein, superior mesenteric vein, and splenic vein before and after the treatment were of significant statistical difference. CONCLUSIONS: Multi-detector row CT portography is an effective screening and evaluating tool for therapeutic endoscopy.

Anti-VEGFR2-conjugated PLGA microspheres as an x-ray phase contrast agent for assessing the VEGFR2 expression.

The primary goal of this study was to evaluate the feasibility of using anti-vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated poly(lactic-co-glycolic acid) (PLGA) microspheres as an x-ray phase contrast agent to assess the VEGFR2 expression in cell cultures. The cell lines, mouse LLC (Lewis lung carcinoma) and HUVEC (human umbilical vein endothelial cell), were selected for cell adhesion studies. The bound PLGA microspheres were found to better adhere to LLC cells or HUVECs than unbound ones. Absorption and phase contrast images of PLGA microspheres were acquired and compared in vitro. Phase contrast imaging (PCI) greatly improves the detection of the microspheres as compared to absorption contrast imaging. The cells incubated with PLGA microspheres were imaged by PCI, which provided clear 3D visualization of the beads, indicating the feasibility of using PLGA microspheres as a contrast agent for phase contrast CT. In addition, the microspheres could be clearly distinguished from the wall of the vessel on phase contrast CT images. Therefore, the approach holds promise for assessing the VEGFR2 expression on endothelial cells of tumor-associated vessels. We conclude that PLGA microsphere-based PCI of the VEGFR2 expression might be a novel, promising biomarker for future studies of tumor angiogenesis.

Preparation, characterization and properties of partially hydrolyzed ethylene vinyl acetate copolymer films for controlled drug release.

In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline hydrolysis of EVA copolymer, characterized by Fourier-transform infrared spectroscopy (FTIR), (1)H NMR and gel permeation chromatography (GPC). Paclitaxel-loaded and drug-free films based on the partially hydrolyzed EVA copolymers were fabricated. The swelling behaviors, crystallinities, mechanical properties of the fabricated films were investigated, and the effects of hydrolysis degree, film thickness and drug loading dose on in vitro drug release from the films were also investigated. In vitro swelling study showed that the swelling of partially hydrolyzed EVA films was greater than the EVA film and the film with higher hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results exhibited that the crystallinity of the polymer increased with increasing hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films, paclitaxel was distributed in amorphous form or molecularly dispersed. In the in vitro drug release test, the film with higher hydrolysis degree and smaller thickness released paclitaxel more quickly. With higher drug loading dose, the drug release rate was larger. The partially hydrolyzed EVA films were applied for drug delivery systems for the first time, and demonstrated to have great capability of controlling drug release thanks to the adjustable hydrolysis degree.

In vivo evaluation of 5-fluorouracil-containing self-expandable nitinol stent in rabbits: Efficiency in long-term local drug delivery.

This 5-fluorouracil (5-FU)-containing stent is fabricated by coating a film, composed of one 5-FU-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer, around a commercial self-expandable nitinol stent. The stents with various drug loadings were implanted into rabbit esophagus, and then 5-FU concentrations in the stent-touching and adjacent segments (including mucosa layer and muscle layer of each segment) of esophagus, serum, and liver were investigated throughout the experiment period. Quantitative analysis of 5-FU was performed by HPLC or LC-MS/MS, while the morphologies of esophageal mucosae by scanning electron microscopy (SEM). The results show that the 5-FU concentration in stent-touching esophageal tissue is overwhelmingly higher than that in serum or liver at all the investigation time points until 45 days. The 5-FU concentration in the stent-touching segment is higher than those in the other segments of esophagus, while the 5-FU concentration in mucosa layer is higher than that in muscle layer for the same segment. With the increase of drug loading, the drug concentrations in esophageal tissues and serum increase, and cellular desquamation of stent-touching epithelial surface become increasingly severe by SEM. Based on the results, the 5-FU-loaded esophageal stent operates long-term local drug delivery with great efficiency.

[Dual interventional therapy for malignant gastroduodenal obstruction].

BACKGROUND & OBJECTIVE: The patients with malignant gastroduodenal obstruction usually have unresectable primary lesion and distant metastasis. Intra-luminal metallic stent implantation followed by intra-arterial chemotherapy via the tumor feeding arteries, so-called "dual interventional therapy", could temporarily relieve obstructive symptoms. This study was to evaluate the clinical safety and efficacy of dual interventional therapy on advanced malignant gastroduodenal obstruction. METHODS: A total of 65 patients with malignant gastroduodenal obstruction underwent dual interventional therapy. Of the 65 patients, 33 had pyloric antrum obstruction, 22 had duodenal obstruction, and 10 had gastroduodenal obstruction with gastrojejunostomal obstruction; 9 had liver metastasis. The patients' survival was analyzed by log-rank test. RESULTS: Stents were successfully implanted into all enrolled patients. No severe adverse events were observed in these patients. The cumulative survival rates at 3, 6, 9, and 12 months after dual interventional therapy were 90%, 66%, 49%, and 28%, respectively. The median survival time was 11.9 months. CONCLUSION: The dual interventional therapy, with metallic stent implantation to relieve malignant obstruction and high-selective intra-arterial chemotherapy to control tumor growth, is a safe, feasible and effective treatment for malignant gastroduodenal obstruction.