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Glossary for Heparin One of the most important developments in the uncovering the full scope of the debacle caused by Baxter’s decision to import Heparin raw material from China, is the research published in the New England Journal of Medicine on April 23, 2008: “Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System” Takashi Kei Kishimoto, Ph.D., et. al. As indicated in the title, this research establishes that the contaminants identified by the FDA in the tainted lots of Heparin, could in fact cause the anaphylactic shock and severe hypotensive events. To understand the full scope of this poisoning, it is important to understand what is described in highly technical terms in this article. Therefore, we have provided a glossary to help the concerned reader, to understand the basic terms used therein. While this is far from a primer in organic chemistry, this glossary has been useful for us, in grasping the technical aspects of these findings. As said in such paper: “The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin–kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins.” We want to acknowledge http:wikipedia.org for the definitional assistance it provide in compiling this glossary (and for its entire concept which makes research on the internet so much easier.) Where appropriate, we have provided links to Wikipedia or other sources. We would also ask anyone who reads this glossary who has a better grasp of the organic chemistry than we do, to email us with suggested additions or improvements to this page. Heparin, a blood thinner made from bi-products of the pig small intestine. Oversulfated chondroitin sulfate (OSCS) is the contaminant found in the tainted heparin, imported from China. This compound appears to be an artificially created compound, which was engineered to have the chemical appearance of Heparin. The raw heparin in the tainted batches was apparently diluted or “cut” with this compound. FDA Release. Contact System A subset of the coagulation process. http://en.wikipedia.org/wiki/Bradykinin Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. Bradykinin is a potent endothelium-dependent vasodilator, causes contraction of non-vascular smooth muscle, increases vascular permeability and also is involved in the mechanism of pain. In some aspects, it has similar actions to that of histamine, and like histamine is released from venules rather than arterioles.
History Bradykinin was detected in the blood plasma of animals after the addition of venom extracted from the Bothrops jararaca (Brazilian lancehead snake), brought by Rosenfeld from the Butantan Institute. The discovery was part of a continuing study on circulatory shock and proteolytic enzymes related to the toxicology of snake bites, started by Rocha e Silva as early as 1939. Bradykinin was to prove a new autopharmacological principle, i.e., a substance that is released in the body by a metabolic modification from precursors, which are pharmacologically active. According to B.J. Hagwood, Rocha e Silva's biographer, "The discovery of bradykinin has led to a new understanding of many physiological and pathological phenomena including circulatory shock induced by venoms and toxins." From the NEJM article: “OSCS-induced C5a generation showed a bell-shaped dose response similar to that found for kallikrein (blood pressure dropping) activation.” http://en.wikipedia.org/wiki/Coagulation Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis (the cessation of blood loss from a damaged vessel) whereby a damaged blood vessel wall is covered by a platelet and fibrin containing clot to stop bleeding and begin repair of the damaged vessel. Disorders of coagulation can lead to an increased risk of bleeding (hemorrhage) and/or clotting (thrombosis). Fibrin: http://en.wikipedia.org/wiki/Fibrin
Excessive generation of fibrin due to activation of the coagulation cascade leads to thrombosis, while ineffective generation predisposes to hemorrhage. Fibrinogen levels can be measured in venous blood. Normal levels are about 150-300 mg/dL. Higher levels are, amongst others, associated with cardiovascular disease (>460 mg/dL). It may be elevated in any form of inflammation, as it is an acute phase protein. Factor XII – A protein necessary for the coagulation of blood. Some examples of glycosaminoglycan uses in nature include heparin as an anticoagulant, hyaluronate as a component in the synovial fluid lubricant in body joints, and chondroitins which can be found in connective tissues, cartilage and tendons. Source: http://en.wikipedia.org/wiki/Glycosaminoglycan Glucosamine - Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. NMR Nuclear Magnetic Resonance Spectroscopy: the preeminent technique for determining the structure of organic compounds, thru using similar concepts as it used in MRI: See: For information on the recall, click here: To contact us, call 800-992-9447. Gordon Johnson is the Owner of the Johnson Law Office. ©Gordon S. Johnson, Jr. 2008 |
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