Potentiation of endogenous nitric oxide with superoxide dismutase inhibits platelet-mediated thrombosis in injured and stenotic arteries

AbstractObjectives. We tested the hypothesis that dismutation of superoxide anion increases endogenous levels of nitric oxide, resulting in inhibition of cyclic variations in blood flow in arteries that are injured and stenotic.Background. Platelet adhesion and aggregation leading to cyclic flow variations might result, in part, from generation of superoxide anion that can deplete endogenously produced nitric oxide.Methods. Spontaneous cyclic flow variations, monitored with a proximal Doppler probe, were induced in the carotid artery of anesthetized rabbits by clamping the vessel with forceps and placing a high grade stenosis at the site of injury. Bovine copper/zinc superoxide dismutase (12 mg/kg body weight, n = 5), a synthetic low molecular weight mimetic (12 mg/kg, n = 8) or buffer vehicle (n = 8) was administered intravenously as divided boluses over 45 min, and the frequency of cyclic flow variations was monitored for 4 h.Results. Cyclic flow variations remained stable for 4 h in vehicle-treated animals (15 ± 1 [mean ± SEM]/30 min at baseline and 16 ± 1/30 min after 4 h, n = 8) but exhibited a marked and persistent reduction in animals given copper/zinc superoxide dismutase (from 14 ± 1/30 min at baseline to 4 ± 1/30 min after 4 h) or the mimetic (from 15 ± 1/30 min at baseline to 3 ± 1/30 min after 4 h, p < 0.005). They were restored in three of four mimetic-treated animals during infusion of NG-monomethyl-l-arginine (100 mg/kg), an inhibitor of nitric oxide production. In addition, levels of cyclic guanosine 5′-monophosphate in platelets were elevated after administration of the mimetic (from 2.4 ± 0.5 fmol/106platelets at baseline to 4.9 ± 0.6 fmol/106platelets 45 min after the mimetic, p < 0.03, n = 6), whereas mean arterial blood pressure was decreased and flow velocity in the carotid artery was increased consistent with mediation of the effect on cyclic flow variations by increased endogenous nitric oxide.Conclusions. Dismutation of superoxide anion appears to attenuate platelet thrombus formation at a site of vessel injury by potentiation of endogenously produced nitric oxide. This approach may have utility to inhibit platelet-rich thrombosis in injured and stenotic arteries where production of superoxide anion is increased

Mediator‐induced activation of xanthine oxidase in endothelial cells

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154271/1/fsb2003013008.pd

Development that works, March 31, 2011

This repository item contains a single issue of the Pardee Conference Series, On March 31, 2011, more than 100 people participated in a conference titled “Development That Works,” sponsored by Boston University’s Frederick S. Pardee Center for the Study of the Longer-Range Future in collaboration with the BU Global Development program. In the pages that follow, four essays written by Boston University graduate students capture the salient points and overarching themes from the four sessions, each of which featured presentations by outstanding scholars and practitioners working in the field of development. The conference agenda and speakers’ biographies are included following the essays.The theme and the title of the conference—”Development That Works”—stemmed from the conference organizers’ desire to explore, from a groundlevel perspective, what programs, policies, and practices have been shown—or appear to have the potential—to achieve sustained, long-term advances in development in various parts of the world. The intent was not to simply showcase “success stories,” but rather to explore the larger concepts and opportunities that have resulted in development that is meaningful and sustainable over time. The presentations and discussions focused on critical assessments of why and how some programs take hold, and what can be learned from them. From the influence of global economic structures to innovative private sector programs and the need to evaluate development programs at the “granular” level, the expert panelists provided well-informed and often provocative perspectives on what is and isn’t working in development programs today, and what could work better in the future

A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout “bins” [5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.Chemistry and Chemical Biolog

Meeting Report: Application of Genotyping Methods to Assess Risks from Cryptosporidium in Watersheds

A workshop titled “Application of Genotyping Methods to Assess Pathogen Risks from Cryptosporidium in Drinking Water Catchments” was held at the International Water Association biennial conference, Marrakech, Morocco, 23 September 2004. The workshop presented and discussed the findings of an interlaboratory trial that compared methods for genotyping Cryptosporidium oocysts isolated from feces. The primary goal of the trial and workshop was to assess the utility of current Cryptosporidium genotyping methods for determining the public health significance of oocysts isolated from feces in potable-water–supply watersheds. An expert panel of 16 watershed managers, public health practitioners, and molecular parasitologists was assembled for the workshop. A subordinate goal of the workshop was to educate watershed management and public health practitioners. An open invitation was extended to all conference delegates to attend the workshop, which drew approximately 50 interested delegates. In this report we summarize the peer consensus emerging from the workshop. Recommendations on the use of current methods by watershed managers and public health practitioners were proposed. Importantly, all the methods that were reported in the trial were mutually supporting and found to be valuable and worthy of further utility and development. Where there were choices as to which method to apply, the small-subunit ribosomal RNA gene was considered to be the optimum genetic locus to target. The single-strand conformational polymorphism method was considered potentially the most valuable for discriminating to the subtype level and where a large number of samples were to be analyzed. A research agenda for protozoan geneticists was proposed to improve the utility of methods into the future. Standardization of methods and nomenclature was promoted