How can I make such pronouncements about neuroprotection, NXY-059, free radical disease, and so forth? And why should anybody pay attention?
I'm a PhD, MD clinical pharmacologist and toxicologist (my board-certification). Stroke researchers may not know me, but they know my work.
E.g., in a 1970 article in Nature, I first proposed that Uric acid substitutes for ascorbate in humans, e.g., as an antioxidant.* Uric acid is now thought to be the single most important extracellular antioxidant
In contrast, my 1972 review article on free radicals and neurological diseases first reports the pro-oxidant properties of urate. This paper proposes that diseases of hyperuricemia such as the Lesch-Nyhan Syndrome involve oxidative stress, a term which had not yet been invented. Later, this was extended to hyperuricemic syndromes in general (1).
Similarly, nearly two decades ago, I stated the since oft-repeated concept that "....the well-established association between high urate levels and atherosclerosis could be a protective reaction ( antioxidant ) or a primary cause ( pro-oxidant ) " (Proctor,1989). Ultimately, this work generated both sides of the current heated dispute between "by generating oxidative stress, uric acid causes stroke" verses "uric acid is an antioxidant neuroprotective agent " (2, 3). Sorry about that. My personal opinion
Uric acid is now in clinical trials in acute ischaemic stroke (4). It was the search for urate-like radical scavengers that did not also mediate radical reactions that led to the spintraps and spin labels.
The 1972 paper also proposes that oxidative stress figures in homocysteine pathogenesis, now of great interest in stroke research. E.g. 4 and 5. Also see these later review articles: "Free Radicals and Disease in Man" and "Free Radicals and Human Disease". Likewise, I was apparently the first researcher to suggest that reactive oxygen species (ROS) have a global messenger role, now dubbed "redox signaling".
Similarly, in an offshoot of our work on free radicals, neurological disease and neuromelanin, we reported the first organic polymer electronic device. This organic semiconductor device is now featured in the rather select Smithsonian Chips collection of early semiconductor devices and documents. This was also the third report of high conductivity in an organic polymer. The fourth such report ( which did not reference the first three ) ultimately won the 2000 Nobel Prize in Chemistry. See www.organicsemiconductors.com.
I am also a coworker of Harry Demopoulos. Harry is generally credited with first establishing the role of reactive oxygen species in acute ischemic stroke, about the time we were publishing papers together. Also see this paper, relating nitric oxide mechanistically to the spintraps and spin labels and implying that NO might act as a neuroprotectant.
Most particularly, I also hold some primary patents for nitroso and nitrone spintraps and nitroxide spin labels to "ameliorate cellular damage to tissues". These have priority dates over two decades ago and include PBN and its derivatives, as well as MNP and its reduction products.
Simply-stated, as much as anyone, I and my friends and coworkers founded this field in its modern guise. So, lissen up-- I might just be right here too...
Peter H. Proctor, PhD,MD
PPS -- though sharing name and, sometimes, attitude-- I'm not this Dr Proctor.
*Here, as elsewhere, I committed the cardinal scientific errors of too early discovery and a poor publicist. So, through no fault of theirs, the concept that uric acid substitutes for ascorbate in humans is sometimes credited to Bruce Ames' group a decade later.
Anyway, most be something about uric acid-- Ames' present group and their occasional collaborator Richard Cutler have also worked on the role of hydrolysis products in the action of PBN and its derivatives. E.g., Dr. Cutler first proposed that hydrolysis products of PBN contribute to its pharmacological action, particularly through release of NO. My friend Dr. Cutler also showed that uric acid levels correlate with longevity in primates (2) and that PBN extends maximum lifespan in mice.
1a.Proctor PH, Kirkpatrick DS, McGinness JE.,Superoxide-dismutase therapy in hyperuricaemic syndromes, Lancet. 1978 Jul 8;2(8080):95.
1b. Proctor PH, Free radicals, uric acid, and human disease, Free Radic Biol Med. 1996;20(5):761-2.
2. Cutler RG, Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species, Arch Gerontol Geriatr. 1984 Dec;3(4):321-48.