Effect of portal hypertension onIn Vivo bile acid-mediated small intestinal mucosal injury in the rat

This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced byin vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5±9.6sem) vs controls 28.1±5.7m, P=0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755±22 vs controls 848±28m, P<0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.This work was supported in part by a grant from the Research Service of the Veterans Administration.     

SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice

GeroScience - Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium...     

Utility of Web-based assessment of patient satisfaction with endoscopy

OBJECTIVES: The dramatic growth of the World Wide Web (Web) holds potential for use in survey distribution and submission. Its use has not previously been studied in the context of patient satisfaction with endoscopy procedures. In this study we compared standard mail, telephone, and Web-based modes of endoscopy satisfaction survey administration with respect to response rate and response content. METHODS: An endoscopy satisfaction questionnaire consisting of seven core items from the modified Group Health Association of America (GHAA-9) was distributed to patients after routine outpatient endoscopy. Patients were randomized to receive the questionnaire by standard mail, telephone, or Web (if applicable). Response rates and satisfaction scores in the groups were compared. The nonresponders to the standard mail and Web surveys were subsequently contacted by telephone to determine their level of satisfaction. RESULTS: Response rates to the telephone survey (81% among those designated as non-Web users and 78% among Web users) and standard mail (75% non-Web users, 67% Web users) were higher than response rate to the Web-based survey (34%) (p < or = 0.0005). There was no significant difference in satisfaction scores among the groups or between satisfaction of nonresponders and responders. CONCLUSIONS: The potential of our Web-based survey was limited by poor response rates. This arose from privacy protection precautions that complicated access to the Web site. Future Web-based strategies for surveying patients will need to be more user-friendly while maintaining the intent of the recent Health Insurance Portability and Accountability Act regulations.     

Endoscopic ultrasound for rectal cancer

The application of EUS has improved the way we evaluate and manage patients with rectal cancer. EUS has substantially greater sensitivity than CT in detecting advanced T stage tumors. Such improved sensitivity results in changes in preoperative therapy that would not otherwise have occurred without EUS. Although the addition of FNA provides little incremental effect on patient management, it carries the most potential for impacting management in those patients with early T stage disease, and its use should be considered in this subgroup of patients. Whether the accurate staging ability of EUS translates into improved outcomes in terms of reduced recurrence rates and ultimately prolonged survival remains uncertain. This will require further long-term outcome studies focusing on the endpoint of tumor recurrence and patient survival.     

Microvascular function at the margins of early experimental myocardial infarcts in isolated rabbit hearts

Summary Injection of low-viscosity resin was used to identify in situ functional blood vessels at the margins of developing regional myocardial infarcts. The ventral interventricular branch (VIB) of the left coronary artery was occluded for 0–240 min in 20 isolated perfused rabbit hearts. After perfusion fixation with glutaraldehyde, resin was injected into the coronary arteries—that injected into the VIB contained dispersed lead dioxide and that injected into the remainder of the heart contained Fat Red 7B dye. This allowed macroscopic and microscopic identification of functional blood vessels. Following transmural freeze fracture, left ventricles were examined using back-scattered electron imaging in a scanning electron microscope. Close to 60% of capillaries in nonischemic myocardium allowed the passage of resin. Thirty minutes of ischemia produced a hyperemic increase to 80%–90% in the proportion of filled vessels. After 60 min, however, a severe reperfusion defect corresponding to the no-reflow phenomenon had developed, with virtually all vessels collapsed and <10% functional. Among the structurally normal myocytes adjacent to the infarct margin there was a significant reduction (to 30%–40%) in the proportion of functional capillaries. This was due to groups of dilated vessels which were not accessible to arterial supply. Although these marginal low-flow regions were of small volume at any one point in time, they seem likely to contribute to the progression of ischemic necrosis, and are probably nonfunctional due to the compression of their venous drainage traversing the infarct.This research was supported by grants from the Medical Research Council of New Zealand and the National Heart Foundation of New Zealand.     

Sequence Conservation of the Region Targeted by the Abbott RealTime HBV Viral Load Assay in Clinical Specimens

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability.     

Comparison of two commercial ELISA systems for evaluating anti‐EBNA1 IgG titers

High IgG titers against the Epstein–Barr virus nuclear antigen, EBNA‐1, have been strongly correlated with the risk of developing multiple sclerosis. ELISAs are used frequently to measure EBNA‐1 titers, however concerns remain regarding the accuracy of results. Ordering absolute results into rank quintiles for analysis may be preferable. Using 120 serum samples, two commercially available ELISAs (produced by DiaSorin and VirionSerion) were compared, both in terms of absolute results and rank quintiles. The positive predictive value of the VirionSerion ELISA was 99.1% when compared to the DiaSorin ELISA, however, the negative predictive value was 64.3%. Sensitivity and specificity were acceptable at 95.5% and 90.0%, respectively. There was poor correlation between absolute results, R² = 0.49; and the kappa coefficient for rank quintiles was low at 0.23. Although sensitivity and specificity appear adequate, the poor negative predictive value and kappa coefficient are of major concern. Care must be taken when selecting assays for experimental use. J. Med. Virol. 85:128–131, 2012. © 2012 Wiley Periodicals, Inc.     

Effects of short-term exercise-training on aortic systolic pressure augmentation in overweight and obese individuals

To determine whether exercise training-induced decreases in blood pressure (BP) can be explained by decreases in aortic systolic pressure augmentation in overweight or obese individuals. Thirty-five sedentary or recreationally active men and women (30–57 years) who were either overweight (40 %) or obese (60 %) completed 6 weeks of exercise training (≥3 days/week; stationary bike and/or treadmill) either preceded (n = 19) or followed (n = 16) by a 6-week control period of no exercise. Aortic augmentation pressure (AP), aortic and peripheral augmentation indices (AIx), and central aortic BP (SphygmoCor) were determined before and after exercise training and a control period. Peak oxygen consumption increased (p = 0.0001) from 27.0 ± 5.1 to 28.8 ± 5.8 mL/(kg min) after 6 weeks of exercise. Exercise training decreased brachial systolic (SBP) and diastolic BP from 142 ± 8/94 ± 8 to 134 ± 11/86 ± 11 mmHg (p < 0.005/p < 0.005); whereas no changes were observed after the control period (141 ± 11/91 ± 9 mmHg, p = 0.81/p = 0.34). Neither AP (baseline: 9.2 ± 4.2 mmHg; after 6 weeks training: 8.7 ± 6.1 mmHg), aortic AIx (baseline: 24.6 ± 11.0 %; after 6 weeks training: 22.7 ± 11.1 %), nor peripheral AIx (baseline: 81.4 ± 16.7 mmHg; after 6 weeks training: 76.4 ± 16.5 mmHg) were modified by exercise training. Although aortic SBP decreased after exercise (132 ± 8 to 124 ± 12 mmHg, p < 0.002), these changes were accounted for by decreases in mean arterial pressure. In overweight or obese individuals, although short-term aerobic exercise training, which improved cardiorespiratory fitness, may produce marked decreases in aortic and brachial BP; these effects are not attributed to alterations in aortic systolic pressure augmentation.     

Synthesis and biochemical evaluation of cephalosporin analogues equipped with chemical tethers

Molecular probes typically require structural modifications to allow for the immobilisation or bioconjugation with a desired substrate but the effects of these changes are often not evaluated. Here, we set out to determine the effects of attaching functional handles to a first-generation cephalosporin. A series of cephalexin derivatives was prepared, equipped with chemical tethers suitable for the site-selective conjugation of antibiotics to functionalised surfaces. The tethers were positioned remotely from the β-lactam ring to ensure minimal effect to the antibiotic''s pharmacophore. Herein, the activity of the modified antibiotics was evaluated for binding to the therapeutic target, the penicillin binding proteins, and shown to maintain binding interactions. In addition, the deactivation of the modified drugs by four β-lactamases (TEM-1, CTX-M-15, AmpC, NDM-1) was investigated and the effect of the tethers on the catalytic efficiencies determined. CTX-M-15 was found to favour hydrolysis of the parent antibiotic without a tether, whereas AmpC and NDM-1 were found to favour the modified analogues. Furthermore, the antimicrobial activity of the derivatives was evaluated to investigate the effect of the structural modifications on the antimicrobial activity of the parent drug, cephalexin.

Tethered β-lactam antibiotics provide insights into designing chemical tools to target specific β-lactamases.