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RBCs distribute oxygen to tissues, but, paradoxically, blood transfusion does not always improve oxygen delivery and is associated with ischemic events. We hypothesized that storage of blood would result in loss of NO bioactivity, impairing RBC vasodilation and thus compromising blood flow, and that repleting NO bioactivity would restore RBC function. We(More)
1 The synthesis of [14C]-debrisoquine hydrochloride and 4-hydroxy-debrisoquine sulphate is described. 2 The metabolic fate and excretion profile in both urine and faeces of 14C-labelled debrisoquine was studied in five healthy human subjects. 3 Investigations showed that the drug is well-absorbed after a single oral dose of 32 mg and quantitatively(More)
Red blood cells (RBCs) act as O(2)-responsive transducers of vasodilator and vasoconstrictor activity in lungs and tissues by regulating the availability of nitric oxide (NO). Vasodilation by RBCs is impaired in diseases characterized by hypoxemia. We have proposed that the extent to which RBCs constrict vs. dilate vessels is, at least partly, controlled by(More)
Nitric oxide (NO) bioactivity is mainly conveyed through reactions with iron and thiols, furnishing iron nitrosyls and S-nitrosothiols with wide-ranging stabilities and reactivities. Triiodide chemiluminescence methodology has been popularized as uniquely capable of quantifying these species together with NO byproducts, such as nitrite and nitrosamines.(More)
OBJECTIVE In preclinical models of peripheral arterial disease the angiogenic response is typically robust, though it can be impaired in conditions such as hypercholesterolemia and diabetes where the endothelium is dysfunctional. Myoglobin (Mb) is expressed exclusively in striated muscle cells. We hypothesized that myocyte specific overexpression of(More)
Hemoglobins are found in organisms from every major phylum and subserve life-sustaining respiratory functions across a broad continuum. Sustainable aerobic respiration in mammals and birds relies on the regulated delivery of oxygen (O2) and nitric oxide (NO) bioactivity by hemoglobin, through reversible binding of NO and O2 to hemes as well as(More)
The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothiopyranoindazoles was carried out by a(More)
A series of N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI) was synthesized for antifilarial evaluation. Condensation of the requisite beta-keto ester (VI) with N-cyanoguanidine afforded 2-pyrimidinylcyanamides (VIIa,b) and(More)
Nitric Oxide in Health and Disease: Abstract Red blood cell-dependent hypoxic vasodilation is largely mediated via the delivery of NO through S-nitrosohemoglobin (Hb-SNO). Hb-SNO is regulated through allosteric and redox mechanisms that are not well understood. Part One of this dissertation explores the biochemical features of Hb micropopulations suggested(More)
A series of N-[4-[[4-alkoxy-3-[(dialkylamino)methyl]phenyl]amino]- 2-pyrimidinyl]-N'-phenylguanidines have been synthesized for antifilarial evaluation. Reaction of the appropriate benzenamines with N-cyanoguanidine, followed by condensation of the resultant N-phenylimidodicarbonimidic diamides (V) with ethyl 4,4,4-trifluoro-3-oxobutanoate provided the(More)