Sucralfate attenuates gastric mucosal lesions and increased vascular permeability induced by ischaemia and reperfusion in rats

Recent evidence suggests that oxygen-derived free radicals are involved in mediating gastric microvascular and parenchymal cell injuries induced by ischaemia and reperfusion. Therefore, the effect of the locally acting anti-ulcer drug, sucralfate, was studied on ischaemia and reperfusion (e.g. induced gastric lesions, intraluminal bleeding, changes in vascular permeability and non-protein sulfhydryl levels in the rat stomach). Allopurinol was used as a known standard antioxidant drug. Rats were subjected to 30 min of gastric ischaemia in the presence of 100 mmol/L hydrochloric acid and reperfusion periods of 15, 30 or 60 min duration. The gastric lesions were assessed microscopically under an inverted microscope. The vascular permeability was quantified by measuring the extravasated Evans blue in the stomach. There were significantly greater numbers of gastric lesions, intraluminal bleeding and leakage of Evans blue during all reperfusion periods as compared with those of ischaemia, with maximum effects occurring at 60 min following reperfusion. Pretreatment with sucralfate (31.25-250 mg/kg, p.o.) or allopurinol (12.5-50 mg/kg, i.p.) 30 min before the procedure, dose-dependently reduced the gastric lesions, intraluminal bleeding, and decreased the vascular permeability induced by ischaemia and reperfusion. Furthermore, sucralfate dose-dependently reverses the ischaemia and reperfusion-induced depletion of mucosal non-protein sulfhydryl levels and inhibited the superoxide radical production in both cell-free xanthine-xanthine oxidase and in the stimulated polymorphonuclear cellular systems. These results suggest that the protection produced by sucralfate against gastric injury may be due to its antioxidant effects.     

On a large-gain theorem

The aim of this paper is to give a general quantitative requirement which the loop gain must satisfy in order to stabilize a given unstable (possibly nonlinear and time-varying) plant, namely that the gain must exceed one.     

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis

Antibiotic treatment options for Burkholderia cepacia infection are limited because of high intrinsic resistance. The problem is complicated by development of cross-resistance between antibiotics of different classes. We isolated antibiotic-resistant mutants by stepwise exposure to chloramphenicol (Chlor) and to trimethoprim/sulphamethoxazole (T/S) for four B. cepacia strains: ATCC13945, Per (clinical isolate), Cas and D4 (environmental isolates). Chlor(r) mutants did not produce chloramphenicol acetyl-transferase. Cross-resistance, defined as greater than four-fold increase in MIC by microtitre dilution method, was consistently seen in both types of mutants. For chloramphenicol-resistant (Chlor[r]) and trimethoprim/sulphamethoxazole-resistant (Tr/Sr) mutants of B. cepacia ATCC13945 and Cas, no MIC change was seen for piperacillin, ceftazidime, rifampicin, gentamicin, tobramycin, polymyxin B or azithromycin. B. cepacia-Per and -D4 mutants showed cross-resistance to ceftazidime and to piperacillin. Comparison of outer membrane protein (OMP) profiles of B. cepacia and their mutants by SDS-PAGE revealed Tr/Sr) mutants to be deficient in a major OMP (molecular weight 39-47 kDa). Tr/Sr mutants also expressed additional OMPs not found in wild type strains at 75-77 kDa for B. cepacia-ATCC13945 and -Cas, and 20-21 kDa in B. cepacia-D4 and -Per. No OMP changes occurred in Chlor(r) mutants. Lipopolysaccharide (LPS) profiles of each type of mutant showed new high and low molecular weight LPS bands. Cross-resistance seems to be mediated by alterations in porin and LPS for Tr/Sr mutants, but only by LPS in Chlor(r) mutants.     

Effect of flexure induced transverse crack and self-healing on chloride diffusivity of reinforced mortar

Cracks in reinforced concrete are unavoidable. Durability is of increasing concern in the concrete industry, and it is significantly affected by the presence of cracks. The corrosion of reinforcing steel due to chloride ions in deicing salts or sea-water is a major cause of premature deterioration of reinforced concrete structures. Although, it is generally recognized that cracks accelerate the ingress of chlorides in concrete, a lack of consensus on this subject does not yet allow reliable quantification of their effects. The present work studies the relationship between crack widths and chloride diffusivity. Flexural load was introduced to generate cracks of width ranging between 29 and 390 μm. As crack width was increased, the effective diffusion coefficient was also increased, thus reducing the initiation period of corrosion process. For cracks with widths less than 135 μm, the effect of crack widths on the effective diffusion coefficient of mortar was found to be marginal, whereas for crack widths higher than 135 μm the effective diffusion coefficient increased rapidly. Therefore, the effect of crack width on chloride penetration was more pronounced when the crack width is higher than 135 μm. Results also indicate that the relation between the effective diffusion coefficient and crack width was found to be power function. In addition, a significant amount of self-healing was observed within the cracks with width below 50 μm subjected to NaCl solution exposure. The present research may provide insight into developing design criteria for a durable concrete and in predicting service life of a concrete structures.     

Conceptual damage-sensitive features for structural health monitoring: Laboratory and field demonstrations

The use of damage-sensitive features to evaluate structural condition or health is a very critical aspect of structural health monitoring. The purpose of this paper is to investigate the potential of two different damage-sensitive features for detecting damage. Different damage scenarios are simulated on a large-scale laboratory structure and a three-span highway bridge for demonstration. The features presented in this paper are the modal flexibility-based deflection and curvature both of which are obtained directly from dynamic properties. In the literature, flexibility associated with mode shapes and mode shapes curvatures have been mostly explored. In this study, multi-input–multi-output dynamic data are used to obtain modal flexibility, which is a close approximation to the actual flexibility. A main novelty is that the curvature is calculated from the deflected shapes using the modal flexibility as opposed to using modal vectors. In this paper, the theory of the methodology is explained and then experimental studies and results are presented. For the experimental studies, the laboratory specimen and the three-span bridge were gradually damaged. It is shown that both deflection and curvature are conceptual and physically meaningful features for damage detection and localization. The issues and the requirements for these features to perform successfully are also presented.     

Substrate-induced conformational change in a trimeric ornithine transcarbamoylase

The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein-protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an L-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.