Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies.

Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.

Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design.

siRNA therapeutics are currently regarded as promising candidates to make a leap forward in the search for treatments of various hard to cure diseases. In order to exploit the full potential of siRNA based therapeutics, development of delivery systems that can efficiently guide the siRNA molecules to their target without major side effects will be the key to success. Lipid based delivery systems, originating from earlier research in the fields of gene delivery, are the most studied candidates for siRNA delivery.

Silica-based monolithic columns versus conventional particle-packed columns for liquid chromatographic analysis of tetracycline, oxytetracycline and chlortetracycline.

The rise of monolithic stationary phases offers to routine and research laboratories several advantages. In spite of their recent discovery, they have rapidly become highly popular separation media for liquid chromatography. Time reduction and economic reasons like e.

Can ultrasound solve the transport barrier of the neural retina?

Purpose: Intravitreal injection of nonviral gene complexes may be promising in the treatment of retinal diseases. This study investigates the permeation of lipoplexes and polystyrene nanospheres through the neural retina and their uptake by the retinal pigment epithelium (RPE) either with or without ultrasound application.

Materials And Methods: Anterior parts and vitreous of bovine eyes were removed.

Wanted and unwanted properties of surface PEGylated nucleic acid nanoparticles in ocular gene transfer.

Ocular gene therapy may offer new hope for severe eye diseases. Many of these ocular diseases are due to a gene defect in the retina, a multi-layered sensory tissue that lines the back of the eye. However, it is well known that the blood-retina barrier and sclera prevent hydrophilic and high molecular weight drugs to reach the retina after systemic or topical application.

Ultrasound-responsive polymer-coated microbubbles that bind and protect DNA.

Ultrasound in combination with microbubbles has recently been considered by gene delivery scientists to be an interesting approach to enhance gene transfer into cells. Its low toxicity and simplicity to apply in vivo without major complications make this technology (sonoporation) especially attractive. Sonoporation of DNA has been evaluated in vivo by the injection of free plasmid DNA (pDNA) together with microbubbles (as used in diagnostic imaging) in the bloodstream.

Vitreous: a barrier to nonviral ocular gene therapy.

Purpose: Intravitreal injection of therapeutic DNA, complexed to nonviral carriers such as cationic liposomes, may be promising in the treatment of many severe retinal eye diseases. However, after intravitreal injection, such DNA/cationic liposome complexes-called lipoplexes (LPXs)-which are typically hundreds of nanometers in size, must first diffuse through the vitreous before they can reach the retina. The aim of this study was to elucidate whether vitreous is a barrier for the LPXs and to find strategies to overcome this barrier.

Three-dimensional fluorescence recovery after photobleaching with the confocal scanning laser microscope.

Confocal scanning laser microscopes (CSLMs) are equipped with the feature to photobleach user-defined regions. This makes them a handy tool to perform fluorescence recovery after photobleaching (FRAP) measurements. To allow quantification of such FRAP experiments, a three-dimensional model has been developed that describes the fluorescence recovery process for a disk-shaped geometry that is photobleached by the scanning beam of a CSLM.