Obstructions of the ureter lumen can originate from intrinsic or extrinsic factors, such as kidney stones, tumours, or strictures. These can affect the physiological flow of urine from the kidneys to the bladder, potentially causing infection, pain, and kidney failure. To overcome these complications, ureteral stents are often deployed clinically in order to temporarily re-establish urinary flow. Despite their clinical benefits, stents are prone to encrustation and biofilm formation that lead to reduced quality of life for patients; however, the mechanisms underlying the formation of crystalline biofilms in stents are not yet fully understood. In this study, we developed microfluidic-based devices replicating the urodynamic field within different configurations of an occluded and stented ureter. We employed computational fluid dynamic simulations to characterise the flow dynamic field within these models and investigated bacterial attachment (Pseudomonas fluorescens) by means of crystal violet staining and fluorescence microscopy. We identified the presence of hydrodynamic cavities in the vicinity of a ureteric occlusion, which were characterised by low levels of wall shear stress (WSS < 40 mPa), and observed that initiation of bacterial attachment occurred in these specific regions of the stented ureter. Notably, the bacterial coverage area was directly proportional to the number of cavities present in the model. Fluorescence microscopy confirmed that the number density of bacteria was greater within cavities (3 bacteria·mm−2) when compared to side-holes of the stent (1 bacterium·mm−2) or its luminal surface (0.12 bacteria·mm−2). These findings informed the design of a novel technological solution against bacterial attachment, which reduces the extent of cavity flow and increases wall shear stress over the stent’s surface.
Varicose veins are chronic venous defects that affect >20% of the population in developed countries. Among potential treatments, sclerotherapy is one of the most commonly used. It involves endovenous injection of a surfactant solution (or foam) in varicose veins, inducing damage to the endothelial layer and subsequent vessel sclerosis. Treatments have proven to be effective in the short-term, however recurrence is reported at rates of up to 64% 5-year post-treatment. Thus, once diagnosed with varicosities there is a high probability of a permanently reduced quality of life. Recently, foam sclerotherapy has become increasingly popular over its liquid counterpart, since foams can treat larger and longer varicosities more effectively, they can be imaged using ultrasound, and require lower amounts of sclerosing agent. In order to minimize recurrence rates however, an investigation of current treatment methods should lead to more effective and long-lasting effects. The literature is populated with studies aimed at characterizing the fundamental physics of aqueous foams; nevertheless, there is a significant need for appropriate product development platforms. Despite successfully capturing the microstructural evolution of aqueous foams, the complexity of current models renders them inadequate for pharmaceutical development. This review article will focus on the physics of foams and the attempts at optimizing them for sclerotherapy. This takes the form of a discussion of the most recent numerical and experimental models, as well as an overview of clinically relevant parameters. This holistic approach could contribute to better foam characterization methods that patients may eventually derive long term benefit from.
Protein adsorption on solid state media is important for the industrial affinity chromatography of biotherapeutics and for preparing materials for self-interaction chromatography where fundamental protein solution thermodynamic properties are measured. The adsorption of three model proteins (lysozyme, catalase and BSA) and two antibodies (a monoclonal and a polyclonal antibody) have been investigated on commercial affinity chromatography media with different surface functionalities (Formyl, Tresyl and Amino). Both the extent of protein immobilised (mg protein/ml media) and the reaction kinetics are reported for a range of reaction conditions, including pH, differing buffers as well as the presence of secondary reactants (glutaraldehyde, sodium cyanoborohydride, EDC and NHS). Compared to the reaction conditions recommended by manufacturers as well as those reported in previous published work, significant increases in the extent of protein immobilisation and reaction kinetics are reported here. The addition of glutaraldehyde or sodium cyanoborohydride was found to be especially effective even when not directly needed for the adsorption to happen. For mAb and pIgG, immobilisation levels of 50 and 31 mg of protein/ml of resin respectively were achieved, which are 100% or more than previously reported. Enhanced levels were achieved for lysozyme of 120 mg/ml with very rapid reaction kinetics (< 1 h) with sodium cyanoborohydride. It can be concluded that specific chromatography resins with Tresyl activated support offered enhanced levels of protein immobilisation due to their ability to react to form amine or thio-ether linkages with proteins. Additionally, glutaraldehyde can result in higher immobilisation levels whilst it can also accelerate immobilisation reaction kinetics.
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