NO is a bioactive free radical produced by NO synthase in various tissues including vascular endothelium. One of the degradation products of NO is HNO2, an agent known to degrade heparin and heparan sulphate. This report documents degradation of heparin by cultured endothelial-cell-derived as well as exogenous NO. An exogenous narrow molecular-mass preparation of heparin was recovered from the medium of cultured endothelial cells using strong-anion exchange. In addition, another narrow molecular-mass preparation of heparin was gassed with exogenous NO under argon. Degradation was evaluated by gel-filtration chromatography. Since HNO2 degrades heparin under acidic conditions, the reaction with NO gas was studied under various pH conditions. The results show that the degradation of exogenous heparin by endothelial cells is inhibited by NO synthase inhibitors. Exogenous NO gas at concentrations as low as 400 p.p.m. degrades heparin and heparan sulphate. Exogenous NO degrades heparin at neutral as well as acidic pH. Endothelial-cell-derived NO, as well as exogenous NO gas, did not degrade hyaluronan, an unrelated glycosaminoglycan that resists HNO2 degradation. Peroxynitrite, a metabolic product of the reaction of NO with superoxide, is an agent that degrades hyaluronan; however, peroxynitrite did not degrade heparin. Thus endothelial-cell-derived NO is capable of degrading heparin and heparan sulphate via HNO2 rather than peroxynitrite. These observations may be relevant to various pathophysiological processes in which extracellular matrix is degraded, such as bone development, apoptosis, tissue damage from inflammatory responses and possible release of growth factors and cytokines.

Objective This study aimed to evaluate the concordance of a new scoring system for neonatal abstinence syndrome (NAS) and NAS scores to the traditional Modified Finnegan Neonatal Abstinence Scoring Tool (M-FNAST) score. The NAS score is based on the physiology of withdrawal, with equal emphasis on behavior, and neurological signs. Study Design The NAS scores for a control group of 202 healthy, term neonates were compared with those for 45 term neonates with NAS. The NAS and M-FNAST scores obtained simultaneously in 45 term neonates with NAS were compared using correlation, linear regression, and receiver operating characteristic curve analysis to determine the validity, reliability, and specificity of the NAS scores. Results The association between the NAS and M-FNAST scores was high (Spearman's correlation, 83%; linear regression, 83%), with an area under the curve of the NAS score of 1.00 (p < 0.01). A cut-off NAS score ≥4 identified NAS neonates with a sensitivity of 100% and specificity of 96%. The values of intraclass correlation, interrater agreement, and Cronbach's α were 0.63, 0.88, and 0.63, respectively. Conclusion The new NAS scoring system is valid, reliable, physiologically based, and correlates closely with the M-FNAST score. The NAS scores may require further validation before its use in clinical practice.

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