Linda’s comments:  I attended a lecture by Dr Martin Pall regarding NO/ONOO and found it extremely interesting.  You can google him and get a large number of articles by Dr Pall.  Well worth your reading time.

Excerpt:

We are excited to present information from the forthcoming book by Martin L. Pall, PhD, who shows that all these conditions – and probably many others – involve the same key biochemical response: elevated levels of nitric oxide (NO) and its oxidant product peroxynitrite (ONOO–), which initiate a biochemical vicious cycle. Although the mechanisms underlying this ongoing NO/ONOO– cycle are well-documented, Dr. Pall presents new information about how this cycle interacts to produce patterns of symptoms. The theory elegantly answers many questions, including: If CFS, MCS, FM, PTSD and GWS have a common biochemical link, why is there such a variety of symptoms? Why do symptoms vary among sufferers of the same condition? What roles do infection, chemical exposure, physical trauma, and severe psychological stress play? How do short-term stressors initiate chronic illness? What are the common symptoms and signs? What is an approach that corrects the cause, rather than treating the symptoms? How does the biochemistry of the NO/ONOO– cycle produce chronic illness? What are the principles underlying the NO/ONOO– cycle mechanism? Can the NO/ONOO– cycle explain other previously unexplained properties of these illnesses? How might 14 additional illnesses/diseases also be caused by the NO/ONOO– cycle etiology? And many more… All this is backed up with more than 1,500 references to scientific literature.

Key Points Symptoms are generated by elevated levels of nitric oxide, peroxynitrite and several other consequences of the NO/ONOO– cycle, such as elevated activity of NF-kappa B, superoxide, inflammatory cytokines and activity of two transmitter systems, the vanilloid receptor and the NMDA receptor. Therapy should focus on down-regulating the NO/ONOO– cycle biochemistry. Peroxynitrite is a potent oxidant, and it or its products initiate oxidative chain reactions, causing damage to both proteins and DNA. When its levels are sufficiently elevated, it can cause programmed cell death (apoptosis), an important mechanism in neurodegenerative diseases. Peroxynitrite attacks several of the important proteins in mitochondria, acting along with superoxide and nitric oxide in lower energy metabolism. Such energy metabolism dysfunction lowers the availability of ATP, the energy currency in cells, and is an important part of NO/ONOO– cycle biochemistry. Much of the mechanism of the NO/ONOO– cycle is local, impacting one tissue but not necessarily impacting an adjacent tissue. Different people suffering from these illnesses may have distinct tissues impacted by NO/ONOO– cycle biochemistry, and this variation in tissue distribution leads to an almost infinite variation of symptoms and signs. This is proposed to be responsible for the extraordinary variation in symptoms and signs reported in comparisons of one patient with another. Conditions caused by the NO/ONOO– cycle are best treated by using agents that are expected to down-regulate NO/ONOO– cycle biochemistry. At least 30 therapeutic agents or classes of agents are available today that are expected to down-regulate cycle biochemistry. Of these 30, clinical trial studies have been performed on 12, and all 12 show evidence of efficacy in treatment of these multisystem diseases or closely related illnesses. Clinical observations and/or anecdotal reports suggest that six additional agents or classes of agents are also effective in treatment.