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KESSLER
Aqueous Iodine Equilibria in Mammalian Iodination ReactionsKessler J, Hooge D Thyroid, Jan 2007, Vol. 17, No. 1 : 19 -24
"Regulatory activity has been demonstrated in two classes of iodinated organic species: thyroid hormones (T3 and T4) and iodinated lipids (ILs), e.g. 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid. The formation of iodinated biomolecules requires iodide oxidation. In mammals iodide oxidation is one of several peroxidase-mediated reactions that serve to reduce hydrogen peroxide. I2 is one of several reaction products formed by mammalian peroxidases during iodide oxidation. I2 forms HOI in an aqueous environment which also has the capacity to iodinate organic species. This manuscript examines the potential relationship between the two classes of known mammalian iodinating species. A model describing iodination pathways for organic species in mammals is advanced. The model predicts the formation of ILs under normal dietary intake of iodine. The model was challenged by characterizing the lipids of hogs maintained on a diet containing normal levels of iodine. Iodinated lipids were found to be present in the fatty acids extracted from the thyroid of these hogs."
The Effect of Supraphysiologic Levels of Iodine on Patients with Cyclic MastalgiaKessler JH.
“"A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted with 111 otherwise healthy euthyroid women with a history of breast pain.... A statistically significant improvement (p < 0.01) associated with dose was observed in the Lewin overall pain scale for all treated groups compared to placebo. Reductions in all three physician assessments were observed in patients after 5 months of therapy in the 3.0 mg/day (7/28; 25%) and 6.0 mg/day (15/27; 18.5%) treatment groups, but not the 1.5 mg/day or placebo group. Patients recorded statistically significant decreases in pain by month 3 in the 3.0 and 6.0 mg/day treatment groups, but not the 1.5 mg/day or placebo group; more than 50% of the 6.0 mg/day treatment group recorded a clinically significant reduction in overall pain. All doses were associated with an acceptable safety profile. No dose-related increase in any adverse event was observed.”
IoGen - Breast Pain Clinical Research Trial
"Symbollon is enrolling patients in a national multi-center, placebo-controlled, double-blinded, randomized Phase III clinical trial for the treatment of moderate or severe breast pain associated with fibrocystic breast disease. The trial drug, IoGen, may help relieve breast pain. The study has been registered with FDA under the Protocol Registration System at ClinicalTrials.gov."
Symbollon provides update on IoGen Phase III Pain StudySymbollon August 9, 2006
"It anticipates closing the enrollment of its IoGen™ Phase III pivotal pain study by yearend. The ongoing IoGen study has over 25 active sites across the United States. Symbollon is planning to conduct a comprehensive advertising campaign during the remainder of 2006 to assist these sites in recruiting subjects for the study by yearend."
Research calls for use of molecular iodine to treat breast cancerSymbollon October 31, 2006
"Symbollon Pharmaceuticals, Inc. (OTCBB: SYMBA) today provided a review of recent independent scientific publications focused on the possible use of molecular iodine, the active agent in Symbollon’s drug, IoGen™, to treat breast cancer. The results of such research identify molecular iodine as a possible treatment for breast cancer. This research recommends the initiation of human clinical trials testing molecular iodine as an adjuvant therapy for breast cancer. "
Iodine's Mechanism of ActionKessler J
"The relationship between iodine intake, thyroid hormones and breast cancer has engaged the interest of clinicians for well over 50 years. Within the past thirty years diverse experimental observations examining (1) the autoregulatory mechanism in the thyroid, (2) the dynamic control of pituitary derived prolactin in patients with fibrocystic breast disease and (2) aqueous iodine chemistry, have provided a mechanistic basis that for the variety of epidemiological, non-clinical and clinical observations related to iodine intake and mammary tissue.
"The thyroid needs a mechanism to protect itself from chronic exposure to high levels of iodine. Observations from a variety of different laboratories indicate that the enzyme peroxidase catalyzes the formation of iodinated polyunsaturated fatty acids, such as arachidonic acid and docosahexaenoic acids, instead of tyrosine at elevated concentrations of iodide. Several of the iodinated lipids formed by peroxidase have been shown to exhibit a broad antiproliferative effect. Iodolactones have been shown to inhibit the production of inositol phosphates induced by epidermal growth factor (EGF); the hydrogen peroxide production by NADPH oxidases; and adenylyl cyclase. Several leading researchers in this field believe that the antiproliferative activity of iodolactones and iodoaldehyes mediate thyroid autoregulation. These iodolipids should be able to be formed in other tissues of the body.
"The formation of these iodinated lipids is reasonable based upon the enzymology of peroxidase and aqueous iodine chemistry. The mechanism of the enzyme peroxidase has been studied for close to 100 years. Between 1940 and 1990 many teams of expert enzymologists around the world attempted to identify how peroxidase catalyzes the formation of thyroid hormones. Despite thousands of published studies we cannot identify a discrete set of experiments that unequivocally identify the mechanistic pathway for thyroid hormone synthesis. An overlooked factor that probably contributes to this difficulty is the characteristics of the oxidized iodide. Hatch developed the first complete set of equations that describe the behavior of the I2 species in an aqueous environment. In the 1980s Gottardi developed a computer program that solves the nonlinear equations describing this equilibrium. It is clear from Gottardi's studies that oxidized iodide species do not behave in a linear manner. That is, the reaction product(s) from the oxidation of iodide by peroxidase can vary depending upon the concentration of the reactants. It is not, therefore, unreasonable that at physiologic levels of iodide tyrosine is iodinated while at elevated levels other iodine species, like I2, are formed. Peroxidase mediated formation of iodinated lipids at elevated iodide concentrations is reasonable from the perspective of iodine chemist since molecular iodine (I2) formation could be expected under these conditions. In fact, Symbollon has used this reaction as the basis of the first product developed by the company
"The requirements for the formation of iodinated lipids are (1) a peroxidase, (2) an elevated concentration of iodide and (3) hydrogen peroxide. These conditions can be met in the mammary gland, oviduct and uterus."
Symbollon Patents for Breast Iodine
More articles and patents by Kessler
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