Early TIPS failure in association with left mesenterico-gonadal spontaneous portosystemic venous shunt; a case report.

Transjugular intrahepatic portosystemic shunt (TIPS) periprocedural thrombosis rates have fallen significantly since the introduction of polytetrafluoroethylene-covered stent grafts. We present a case of a cirrhotic patient with portal hypertension presenting with early TIPS thrombosis in association with an underlying competing spontaneous left mesenterico-gonadal venous shunt, an uncommon variant of spontaneous portal systemic shunt (SPSS). The patient presented with bleeding distal duodenal varices refractory to endovascular therapy, and although a successful TIPS procedure was performed for this indication, early thrombosis was determined by follow-up abdominopelvic computed tomographic angiography (CTA) scan. Despite undergoing a standard TIPS revision procedure, blood flow through the TIPS remained hepatofugal. During a TIPS revision, portal vein angiography revealed competing large inferior mesenteric vein (IMV) varices shunting into the left renal vein via the left gonadal vein. The initial abdominal CTA was later reviewed by a non-invasive cardiovascular radiologist, and the presence of the competing left mesenterico-gonadal shunt was retrospectively identified. Radiologists interpreting CTA exams should be aware of SPSS generally and mesenterico-gonadal shunts specifically. Pre-procedural knowledge of underlying SPSS can affect post procedural outcomes and should be emphasized in the final CTA report.

Congenital intravascular abdominal aortic band initially thought to be a metallic foreign body: Characterization using microanatomical CT reconstruction technique.

We present a patient with the initial misdiagnosis of a metallic foreign body in the abdominal aorta. Computed tomographic angiography utilizing microanatomical reconstruction technique revealed the structure to instead be a partially calcified abdominal aortic congenital fibrous band. Most congenital fibrous bands spanning the aortic lumen are proximal within the aorta and are thought to be supportive structures of the aortic valve leaflets. Congenital fibrous bands distal to the sinotubular junction are quite rare.

Tailoring of chitosans for gene delivery: novel self-branched glycosylated chitosan oligomers with improved functional properties.

Chitosan is a promising biomaterial with an attractive safety profile; however, its application potential for gene delivery is hampered by poor compatibility at physiological pH values. Here we have tailored the molecular architecture of chitosan to improve the functional properties and gene transfer efficacy of chitosan oligomers and have developed self-branched glycosylated chitosan oligomer (SB-TCO) substituted with a trisaccharide containing N-acetylglucosamine, AAM. SB-TCO was prepared by controlled depolymerization of chitosan, followed by simultaneous branching and AAM substitution. The product was fully soluble at physiological pH and complexed plasmid DNA into polyplexes of high colloidal and physical stability. SB-TCO displayed high transfection efficacy in HEK293 cells, reaching transfection efficiencies of up to 70%, and large amounts of transgene were produced. Gene transfer efficacy was confirmed in HepG2 cells, where gene expression levels mediated by SB-TCO were up to 10 and 4 times higher than those obtained with unsubstituted and substituted linear oligomers, respectively. The rapid onset of transgene expression in both cell lines indicates efficient DNA release and transcription from SB-TCO polyplexes. In comparison with 22 kDa linear PEI-based transfection reagent used as the control, SB-TCO possessed higher gene transfer efficacy, significantly lower cytotoxicity, and improved serum compatibility.

Targeted gene delivery with trisaccharide-substituted chitosan oligomers in vitro and after lung administration in vivo.

The aim of this study was to improve the gene delivery efficacy of chitosan oligomer polyplexes by introducing a trisaccharide branch that targets cell-surface lectins. For this purpose, chitosan oligomers were substituted by a trisaccharide with the N-acetylglucosamine residue at the free end, and the ability of the trisaccharide-substituted chitosan oligomers (TCO) polyplexes to transfect various cell lines in vitro and lung tissue after in vivo administration to mice was investigated. Live-cell confocal microscopy showed improved cellular uptake in HEK 293 cells (11-fold, p<0.001) for the TCO polyplexes compared with the linear chitosan oligomers. Colloidal stability was also enhanced with the substituted form, which suggests that the trisaccharide branch stabilised the polyplexes by means of a steric stabilisation mechanism. Interestingly, gene expression levels in the human liver hepatocyte (HepG2) cells were 10-fold higher with the TCO polyplexes than those mediated by polyethyleneimine. A similar improvement was obtained in a human bronchial epithelial cell line (16HBE14o-). Transfection with the TCO was significantly inhibited (by 30-80%), for all the cell lines tested, in the presence of the free trisaccharide branch, confirming lectin-mediated uptake. Finally, in vivo studies showed that, 24 h after lung administration to mice, luciferase gene expression was 4-fold higher with the TCO than with the corresponding linear chitosan oligomers.

Chitosan and the mucosal delivery of biotechnology drugs.

Recent human and animal studies have indicated that chitosan-based delivery systems are promising alternatives to conventional formulation approaches for the mucosal delivery of biotechnology drugs, such as proteins and genes. Here, we briefly analyze the current chitosan literature, review promising in vivo studies, discuss the inherent biological properties of chitosan and present new selected technological advances using chitosan delivery systems.:

A miniaturized nebulization catheter for improved gene delivery to the mouse lung.

BACKGROUND: The available methods for administration of gene delivery systems to the lungs of small animals via nebulization have several drawbacks. These include lack of control over the delivered dose and a negative impact on the stability of the formulation. This paper describes a new nebulization catheter device for the administration of plasmid-based gene delivery systems (polyplexes) as aerosols to the mouse lung in vivo. METHODS: The physical stability of naked pDNA and polyplexes formulated with chitosan oligomers and PEI was examined following nebulization with the catheter device. We also examined the in vitro transfection efficiency of the polyplexes recovered after nebulization. Lung distribution and gene expression after administration of the selected gene delivery systems to the mouse lung were also investigated. RESULTS: In contrast to previously described nebulization methods, the structural integrity of the unprotected naked pDNA was maintained following nebulization by the catheter device, which indicates relatively mild nebulization conditions. In addition, the nebulization procedure did not affect the physical stability of the formulated polyplexes. Small volumes of the pDNA aerosol (10-20 microl) were delivered in a highly controlled and reproducible manner. The aerosol droplet size varied with the molecular weight of the polycations. Aerosol delivery via this method resulted in improved lung distribution of pDNA polyplexes and a six-fold increase in the efficiency of gene delivery in vivo over that seen with the commonly used intratracheal instillation method. CONCLUSION: The use of the nebulization catheter device provides a promising alternative for aerosol gene delivery to the mouse lung.