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461.
ObjectiveTo establish and evaluate a standardized method of targeted, intrabronchial drug delivery in pigs.Study designRandomized controlled trial.AnimalsA total of 16 German Landrace pigs (Sus scrofa), age range 12?16 weeks, and weighing 28?35 kg.MethodsThe animals were anaesthetized, intubated, and instrumented with extended cardiovascular monitoring. Lung injury was induced by administering via a flexible fibre-optic endoscope using 100 mL saline solution containing either 20 mg of Escherichia coli lipopolysaccharide (E. coli LPS) (n = 8) or no additive (sham, n = 8) into the two distal mainstem bronchi. The animals were monitored for 8 hours and arterial oxygenation, inspiratory pressure and arterial blood pressure were measured repeatedly. Post-mortem, lung tissue was prepared for histologic damage scoring and determination of proinflammatory cytokines Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). Statistical analyses were performed using inter-group analysis of variance and Student’s t tests. Data are presented as mean ± standard deviation. A p value <0.05 was considered significant.ResultsThe targeted application of LPS led to significant deterioration of oxygenation consistent with mild-to-moderate acute respiratory distress syndrome (ARDS) and hypotension (Horowitz ratio: sham 2 hour, 300 ± 39; LPS 2 hour, 193.7 ± 52; p < 0.001). Histologic analyses identified increased inflammation and oedema in the tissues of the animals in the LPS group IL-6 sham: 6.4 ± 4.4 × 10–5 pg mL–1; IL-6 LPS: 2.8 ± 2.4 × 10–4 pg mL–1, p = 0.015.ConclusionsThe targeted application of agents via flexible fibre-optic endoscopy is a valid, reliable method of causing controlled lung damage in a porcine model. The data presented suggest the feasibility and possible advantages of controlled application and could expand the array of techniques used to help understand the critical condition of ARDS. In addition, a targeted approach could help reduce animal numbers used for this purpose.  相似文献   
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The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.  相似文献   
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Agroforestry Systems - In the original publication of the article, the article title was incorrectly published.  相似文献   
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Zusammenfassung Es werden verschiedene Methoden zur Resistenzprüfung von Kartoffelknollen gegen den Erreger der Braunf?ule (Phytophthora infestans (Mont.) de Bary) miteinander verglichen. Drei Prüfungen werden mit Knollenscheiben durchgeführt; bei einem Test werden Knollenh?lften verwendet. Am besten geeignet erscheint ein modifizierter Test nach Lapwood, der auch die Wundreaktion der Knollen in die Prüfung mit einbezieht.  相似文献   
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Aroma compound properties in food matrices, such as volatility and diffusivity, have to be determined to understand the effect of composition and structure on aroma release and perception. This work illustrates the use of mass transfer modeling to identify diffusion and partition properties of ethyl hexanoate in water and in carrageenan matrices with various degrees of structure. The comparison of results obtained with a diffusive model to those obtained with a convective model highlights the importance of considering the appropriate transfer mechanism. Modeling of the preliminary experimental steps ensures correct estimation of the conditions for the main aroma release step. The obtained values of partition and diffusion coefficients are in agreement with those found in the literature (either experimentally determined or predicted by theoretical equations) and demonstrate that the structure level of carrageenan matrices has little influence on diffusion properties of ethyl hexanoate (less than 20%).  相似文献   
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