ࡱ> VXU #.bjbjcTcT 4N>>#&``L4$f7c$e$e$e$e$e$e$$J&(f$}}}$$ccc}:c$c}c$cc<#s^O$$0$R)NR)R)#L6c(,T)$$c$}}}}R)` i: NITROXIDE PAPER Product: NitrOxide (Giddy Up Go and Equine Science Solutions) Purpose: Arginine Derived Nitric Oxide (ADNO) Equine Laminitis treatment Design Objective: To provide precursors to ADNO, to oppose nitric oxide free radical oriented oxidative stress, to regulate nitric oxide, and to use nitric oxide signaled vasodilation as a means to deliver laminitis nutrients to lacking regions in the body due to inefficient blood flow. Step 1 - a fasting dose with our proven Biosnergistic uptake system, to get nutrients into the blood stream quickly and efficiently. Step 2 - now that you have all those elements in the blood stream the body will use those elements along with NOS (Converter) to produce NO signaled vasodilatation, the bodys own nutrient delivery system Step 3 - Stanford blood flow pathway; Elements: Arginine and other nitric oxide precursors, network antioxidants, flavanoids, vitamins, minerals, and whole herbs. Technology: NitrOxide utilizes our proprietary nitric oxide delivery system clinically studiedand proven to produce ADNO, specifically endothelial derived nitric oxide,in excess of 30 minutes (up to 4 hours). Such nitric oxide production (over the 30 minute threshold) promotes vasodilation, which increases blood flow, oxygen delivery, and nutrient delivery. Mechanisms and success of our nitric oxide pathway products are by virtue of translation of numerous studies showing applications of arginine, nitric oxide and formula ingredients (amino acids, vitamins, minerals, nutrients and herbs). Process: NitrOxide works by increasing endothelial and neuronal nitric oxide system wide. More normalizedendothelial nitric oxide levels increasevasodilation, laminar blood flow, decreases laminar swelling, and supports recovery from laminitis. Clinical Overview: Laminitis causes inflammation in thelaminae, leading to rotation or sinking of the coffin bone.The main sign of laminitis is extreme pain, mostly in the front feet. Earlier signs from suffering horses include shifting weight back and forth and a reluctance to walk as the pain becomes more severe. Eventually, the horse will lie down for prolonged periods, leading to pressure sores (Eades, LSU). Moore and Eades (LSU Study, attached) believe the initiating factor in the onset of laminitis is an imbalance in blood flow to laminae caused by decreased production of nitric oxide (which normally relaxes blood vessels and increases blood flow) and increased release of endothelin-1 (which causes blood vessel contraction and subsequent decreases in blood flow). This imbalance ultimately leads to decreased laminar blood flow, laminar swelling, tissue death, and subsequent separation of the laminae. Similar to diabetes, where decrease in nitric oxide production results in peripheral neuropathies, numbnessand poor wound healing,equine Cushings almost inevitably results in laminitis,further illustratingthe relationship between laminitis and nitric oxide deficiency. Nitric Oxide (NO): NO, is a short-lived, endogenously produced gas that acts as a signaling molecule in the body. Signal transmission by a gas, produced by one cell, which penetrates membranes and regulates the function of other cells is an entirely new principle for signaling in animal organisms. NO in its endothelial form is well studied as a system wide blood vessel vasodilator, allowing oxygen and nutrients to reach peripheral and central body areas. Nobel Prize Research: In 1998 the Nobel Prize in Physiology or Medicine was awarded to Robert F. Furchgott, Louis Ignarro, and Ferid Murad for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system, particularly in signaling the relaxation of endothelial tissue in cardiovascular vessels (vasodilation). This discovery determined the mechanism ofnitroglycerine as producing nitric oxide. Endothelial Nitric Oxide Pharmaceuticals: Nitroglycerine, Viagra, Cialis and Levitra. Concern has arisen regarding using these applications for sustained blood flow issues such as laminitis due to oxidative stress, lack of NO regulators, and cGMP inhibitor effects (blood flow is impeded from return) caused by Viagra, Cialis and Levitra. Current Pharmaceuticals for Laminitis: Nitroglycerine cream Isoxsuprine Attached Articles: LSU Laminitis Article Blood Vessel Health References: 1. Cooke, J.P., Is atherosclerosis an arginine deficiency disease? J. Investigative Medicine, 46(1998) 377-380. 2. Cooke, J.P., Role of nitric oxide in progression and regression of atherosclerosis, West J. Med, 164 (1996) 419-424. 3. Fields, C.E. and Makhoul, R.G., Vasometer tone and the role of nitric oxide, Semin. Vascular Surgery., 11 (1998) 181-192. 4. Lyons, D., Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease, Int. J. Cardiology., 62 Suppl 2 (1997) S101-S109. Equine Laminitis References:  HYPERLINK "https://www.thehorse.com/ViewArticle.aspx?ID=9247" \t "_top" The Horse: Bluegrass Laminitis Symposium: What we Know About Laminitis When it comes to laminitis, everyone's got a pet theory--their favorite ... in blood flow and nitric oxide concentrations when nitroglycerine was given ... https://www.thehorse.com/ViewArticle.aspx?ID=9247 HYPERLINK "http://www.thehorse.com/ViewArticle.aspx?ID=634" \t "_top" The Horse: Nitroglycerine "Nitric Oxide and equine laminitis: topical speculation or scientific fact," in Equine Veterinary Journal. "Nitric Oxide donors as treatment for grass ... www.thehorse.com/ViewArticle.aspx?ID=634 HYPERLINK "http://www.thehorse.com/ViewArticle.aspx?ID=1394" \t "_top" The Horse: LSU Veterinarians Recieve Grant To Help Fight Laminitis Each year veterinarians worldwide wrestle with laminitis, a critical, ... imbalance in blood flow to laminae caused by decreased production of nitric oxide, ...  HYPERLINK "http://www.thehorse.com/ViewArticle.aspx?ID=1394" www.thehorse.com/ViewArticle.aspx?ID=1394 HYPERLINK "http://www.thehorse.com/viewarticle.aspx?ID=451" \t "_top" The Horse: Photo Therapy: AKA Therapeutic Laser Nitric oxide might be the molecule responsible for the effects of nitroglycerin in treating the post traumatic laminitis. Chris Pollitt, BVSc, PhD,  HYPERLINK "http://www.thehorse.com/viewarticle.aspx?ID=451" www.thehorse.com/viewarticle.aspx?ID=451 HYPERLINK "http://www.thehorse.com/TopicSearch/Default.aspx?ID=210&nID=12&n=Joint%20Supplements" \t "_top" The Horse: Nutrition/Supplements | Joint Supplements "During exercise, free radicals such as nitric oxide and carbon monoxide are generated that are .... while others gain weight and become prone to laminitis. ... www.thehorse.com/TopicSearch/Default.aspx?ID=210&nID=12&n=Joint%20Supplements HYPERLINK "http://www.thehorse.com/TopicSearch/Default.aspx?ID=411&nID=43&n=Current%2F+Archived+News" \t "_top" The Horse: News | Current/ Archived News "During exercise, free radicals such as nitric oxide and carbon monoxide are ..... 10 will include an in-depth session on laminitis for the practitioner, ... www.thehorse.com/TopicSearch/Default.aspx?ID=411&nID=43&n=Current%2F+Archived+NewsLSU Laminitis Research Press Release by: Stephanie L. Church, Copy/Features Editor November 02 2001, Article # 1064 Two equine researchers at the Louisiana State University (LSU) School of Veterinary Medicine recently received a USDA National Research Initiative Mech-anisms of Disease Grant to study the cause of laminitis. This disease causes chronic lameness or death in countless horses every year. Despite the high number of patients veterinarians examine and treat for the condition, prevention and effective treatment options still are unavailable. Rustin Moore, DVM, PhD, Dipl. ACVS, director of the Equine Health Studies Program and Associate Professor of Equine Surgery, and Susan Eades, DVM, PhD, Dipl. ACVIM, Associate Professor of Equine Medicine, received the $216,000 grant for their proposal, "Pathophysiologic and therapeutic implications for endothelin in equine laminitis." Through a two-year study, they will attempt to determine if the initial factor leading to laminitis is an imbalance in blood flow to the laminae, which hold the hoof wall to the coffin bone. Laminitis causes inflammation to these laminae, leading to rotation or sinking of the coffin bone. Once this occurs, pain is permanent until the hoof grows back into normal alignment with its inner structures, which can take a year or more. If the hoof does not re-align, the pain will continue and the horse might have to be euthanized. "The main sign of laminitis is extreme pain, mostly in the front feet," said Eades. "Earlier signs from suffering horses include shifting their weight back and forth and a reluctance to walk as the pain becomes more severe. Eventually, the horse will lie down for prolonged periods, leading to pressure sores." Moore and Eades believe the initiating factor in the onset of laminitis is an imbalance in blood flow to laminae caused by decreased production of nitric oxide (which normally relaxes blood vessels and increases blood flow) and increased release of endothelin-1 (which causes blood vessel contraction and subsequent decreases in blood flow). This imbalance ultimately leads to decreased laminar blood flow, laminar swelling, tissue death, and subsequent separation of the laminae. "There has been substantial research conducted on laminitis, which has unraveled important information regarding its pathogenesis," said Moore. "However, there is a missing link in the understanding of the disease, keeping us from effective and reliable prevention and treatment. We believe the pathway we are investigating may provide this missing link." &1NR[\mz C D 8 9 D ? 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