Bladder outlet obstruction induces marked morphological, functional, and metabolic changes within the urinary bladder. Recent studies indicate that there is a close correlation between the contractile dysfunction induced by partial outlet obstruction and a marked decrease in mitochondrial oxidative activity of the hypertrophied bladder tissue. The current study investigates the effect of partial outlet obstruction on adenine metabolism within the bladder tissue. After transport into the cell, adenine becomes available as a substrate for adenine phosphoribosyl transferase (APRT), the enzyme that catalyses the non-mitochondrial conversion of adenine into AMP. Subsequently, AMP is phosphorylated to ADP, the phosphate acceptor in mitochondrial oxidative phosphorylation. The results of these studies demonstrate that partial outlet obstruction induces a significant increase in 14C-adenine uptake into the urinary bladder smooth muscle which in turn provides substrate for APRT and results in an increase in 14C-AMP synthesis. In contrast, the rate of incorporation of adenine into ATP+ADP was similar for both control and obstructed tissue. The activity of APRT was not significantly different in control and obstructed tissue. 相似文献
The development and formulation of core–shell latex‐based adhesives to improve the adhesion of aluminium to poly(ethylene terephthalate) (PET) films and enhance the permeability of the final laminate to oxygen and water is described. All particles have a soft acrylic component (the shell in core–shell particles) to improve adhesion, and occasionally a hydrophobic core to enhance the permeability. The performance of the different latexes is compared to that of a commercially available reference material. The coatings formed by core–shell nanoparticles present a lower permeability to water than the particles synthesized in the absence of the seed, while the permeability to oxygen is found to be mainly related to the correct deposition of the metallic layer. In terms of the industrial formulation, it is found that a limited amount of a wetting agent (WA) is needed to ensure the correct spreading of the latex onto the PET substrate because of the low levels of surfactant used for the latex production. This compound has a positive effect on the adhesive strength of the coating. A curing agent also improves barrier properties, but the optimal level of this compound is dependent on the degree of crosslinker used in the base latex. 相似文献
Poorly soluble drugs constitute more than 60% of currently marketed pharmaceuticals with over two-thirds of promising new chemical entities failing to enter a clinical setting due to solubility issues. Although oral formulations have made some impact, alternative enhancement strategies for administration of such molecules are actively sought. Over the last decade, innovation on a global scale has enabled the expansion of the frontiers of microarray patches (MAPs) further than ever before. Initially designed to load low doses of hydrophilic and potent therapeutic agents, MAPs are now becoming a viable strategy for the immediate and long-acting delivery of poorly soluble drugs through the skin. This together with the advantages of transdermal administration over the oral and parenteral routes, make of MAPs an appealing platform for the development of products with increased patient compliance. Undoubtedly, MAPs will soon become a readily available therapeutic alternative, and experts from academia, industry and regulatory bodies are working together aiming to facilitate the progression of MAPs toward safe and effective clinical use. This review aims to highlight the ability of MAPs to deliver poorly soluble actives, discuss the mechanisms behind in-skin drug absorption, and evaluate the future direction of the field. 相似文献
Summary: It was demonstrated that it is possible to produce prepolymers with a number‐average degree of polymerisation on the order of 5–40 directly in a liquid‐liquid dispersion in less than three hours. It was also shown that prepolymers made via this route and rapidly crystallised by the addition of a dispersant at ambient temperature are more porous than prepolymers made in an industrial liquid melt process.
SEM micrograph of prepolymers pLL‐PTA with \overline {DP} _{\rm n} = 28, dp ∈ 63–125 μm. 相似文献
Within the context of a generalized coupling model we can support the hypothesis that, while the mode of relaxation for self diffusion (D) and shear flow (η) are the same, the entanglement interactions are different. We assume that there are two distinct coupling parameters nD and nη for self diffusion and shear flow respectively. The model predicts the molecular weight and temperature dependences to be scaled by the relevant coupling parameters as: for melts with Arrhenius temperature dependences. We have found that nn=0.43 and 0.42 for polyethylene (PE) and hydrogenated polybutadiene (HPB) which scale η as M3.5 and M3.4. Also the apparent flow activation energies of 6.35 kcal mole?1 for PE and 7.2 kcal mol?1 for HPB scale to primitive activation energies Ea of 3.6 and 4.2 kcal mole?1 for PE and HPB respectively. On the other hand the M?2 dependence of D results in nD=1/3. Then the reported activation energies for self-diffusion in PE and HPB of 5.49 and 6.2 kcal mole?1 scale to primitive activation energies of 3.7 and 4.1 kcal mole?1, respectively. 相似文献
Nitrogen (N) is the most limiting nutrient in crop production. Legumes such as red clover can provide N through biofixation, but securing nitrogen in soil for subsequent crop production must also be considered. Variety selection and management in red clover cropping can influence soil mineral nitrogen (SMN) availability. A field trial to investigate this was conducted with six varieties, under one and two cut management, over 2 years. Dry matter (DM) and N yield, Sclerotinia resistance and SMN availability were assessed. Low DM and N yields (1.6–2.4 t DM ha?1 and 54–83 kg N ha?1) in the first year of cultivation allowed ~?40 kg N ha?1 to become available, but high DM and N yields (10.2–14.6 t DM ha?1 and 405–544 kg N ha?1) allowed ~?20 kg N ha?1 to become available. Wetter weather in 2015 caused significantly more SMN losses than 2016 (20 kg N ha?1 in 2015 and 5 kg N ha?1 in 2016). The varieties Amos, Maro and Milvus lost significantly more SMN in the winter period, which may have been caused by more severe infection of Sclerotinia (these varieties were 50–80% more severely infected other varieties). Varietal effect was non-significant for winter losses in 2016, where no significant varietal differences in Sclerotinia infection were observed. 1 cut made ~?41 kg N ha?1 available in the growing season of 2015, whilst 2 cut made significantly less (37 kg N ha?1). Cutting was non-significant in 2016 but 1 cut was less susceptible to losses in the winter period. Cutting in 2015 did not significantly affect herbage DM and N yields in the first or second cut of 2016. 相似文献
Carbonic anhydrases (CAs) are implicated in a wide range of diseases, including the upregulation of isoforms CA IX and XII in many aggressive cancers. However, effective inhibition of disease‐implicated CAs should minimally affect the ubiquitously expressed isoforms, including CA I and II, to improve directed distribution of the inhibitors to the cancer‐associated isoforms and reduce side effects. Four benzenesulfonamide‐based inhibitors were synthesized by using the tail approach and displayed nanomolar affinities for several CA isoforms. The crystal structures of the inhibitors bound to a CA IX mimic and CA II are presented. Further in silico modeling was performed with the inhibitors docked into CA I and XII to identify residues that contributed to or hindered their binding interactions. These structural studies demonstrated that active‐site residues lining the hydrophobic pocket, especially positions 92 and 131, dictate the positional binding and affinity of inhibitors, whereas the tail groups modulate CA isoform specificity. Geometry optimizations were performed on each ligand in the crystal structures and showed that the energetic penalties of the inhibitor conformations were negligible compared to the gains from active‐site interactions. These studies further our understanding of obtaining isoform specificity when designing small molecule CA inhibitors. 相似文献