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Iranian J Publ Health, 2006, Vol. 35, No. 1, pp.58-62.
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Figure 1 shows the TTO-1, IRL, and TTO-2 curves of one eye of a 21-year-old healthy volunteer, whereas Figure 2 shows the curves of the affected eye of a 73-year-old patient with latent herpetic keratitis. Note the difference between the first fluorescein decay TTO-1 ; in Figures 1 and 2. The data of the participants and the results of the measurements are shown in Table 1 One of the healthy volunteers was not accepted because he had giant papillary conjunctivitis. There is a discrepancy in the numbers of healthy and affected eyes in the patients, because there was one patient with a glass eye, one with a corneal defect in the second eye, and one with both eyes affected. The data from all groups were normally distributed P 0.41 ; . The TTO-1, IRL, and TTO-2 data in the left and right eyes of the healthy control subjects in our study were not significantly different, which indicates similar left and right eye measurements P 0.47, P 0.45, P 0.29, respectively ; . There were no differences in the TTO-1, IRL, and TTO-2 data between the.
Investigation of the relative expression of PK-C mRNAs has been hampered by the fact that their abundance in the cell is extremely low. We have therefore established a highly sensitive RNase protection assay specific for human PK-C a, .82, and y mRNA. The method enables reliable quantitation and as little as one copy per cell of specific mRNA can be detected in RNA from lo7cells Fig 1 ; . We have expressed our results, where possible, as relative copy number per cell of the specific mRNA of interest, taking into account the significant reduction of the total RNA and isoniazid.
Isoflavones--on bone mass loss in the early years after menopause. J North Menopause Soc 1998; 5 1 ; : 9-15. Gerhard M, Walsh BW, Tawakol A et al: Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation 1998; 98 12 ; : 11581163. Giovannucci E, Stampfer MJ, Colditz GA et al: Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998; 129 7 ; : 517-524. Gordon J: SSRIs and St John's Wort: possible toxicity? Fam Physician 1998; 57 5 ; : 950-953. Grodstein F, Manson JE & Stampfer MJ: Postmenopausal hormone use and secondary prevention of coronary events in the nurses' health study. a prospective, observational study. Ann Intern Med 2001; 135 1 ; : 1-8. Halama P: Ginkgo biloba. Wirksamkeit eines Speczialextrakts bei Patienten mit zerebraler Insuffizienz. Muench Med Wochenschr 1991; 133 12 ; : 190-194. Hammond T & Whitworth J: Adverse reactions to ginseng letter ; . Med J Aust 1981; 1: 492. Hansten PD & Horn JR: Drug Interactions. Lea & Febiger, Philadelphia, PA, USA, 1989. Hansten PD: Effects of vitamins on drug action. Drug Interactions Newsletter 1981; 1: 35-38. Harrer G & Sommer H: Treatment of mild moderate depressions with Hypericum. Phytomed 1994; 1: 3-8. Harrer G, Schmidt U, Kuhn U et al: Comparison of equivalence between the St Johns Wort extract LoHyp-57 and fluoxetine. Arzneimittelforschung 1999; 49 4 ; : 289-296. Harris TB, Savage PJ, Tell GS et al: Carrying the burden of cardiovascular risk in old age: associations of weight and weight change with prevalent cardiovascular disease, risk factors, and health status in the Cardiovascular Health Study. J Clin Nutr 1997; 66 4 ; : 837-844. Hirata JD, Swiersz LM, Zell B et al: Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997; 68 6 ; : 981-986. Hoelzl J & Ostrowski E: Analysis of the essential compounds of Hypericum perforatum. Planta Med 1986; 6: 531. Hofferberth B: Einfluss von Ginkgo biloba-Extrakt auf neurophysiologische und psychometrische Messergebnisse bei Patienten mit hirnorganischem Psychosyndrom. Eine Doppelblindstudie gegen Plazebo German ; . Arzneimittelforschung 1989; 39 8 ; : 918-922. Hunter D & Frumkin A: Adverse reactions to vitamin E and aloe vera preparations after dermabrasion and chemical peel. Cutis 1991; 47 3 ; : 193-196.
Co-administration of the isoflavone together with an uterine tissue estrogen agonist serm prevents or minimizes the development of endometrial cancer by preventing or minimizing serm induced uterotrophic effects and vasodilan.
159 Dangers of Dietary Isoflavones at levels above those found in traditional diets The Risks Of Abandoning "The Precautionary Principle" by Soy Online Service . : soyonlineservice.co.nz "Soy - Abundance Of Health Hazards" . : mayanmajix soy01 . 159.
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Values are mean SE. Initial body weight recorded at time of ovariectomy and middle cerebral artery occlusion MCAO ; body weight recorded 2 wk after ovariectomy and isoflavone-free IF ; or high-soy S ; diet on day of MCAO. * Significantly different from initial body weight within group, P 0.05. Significantly different from IF-placebo P ; and S-P, P 0.05.
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Osteoporosis An acceleration of bone loss occurs after the menopause, increasing the risk of osteoporosis. The usual treatment for osteoporosis includes hormone therapy. It has been observed that there is a lower incidence of osteoporosis and hip fractures in south east Asian countries where there is a greater dietary intake of phytoestrogens and it has been suggested that phytoestrogens such as genistein may provide protection from bone loss, as demonstrated in the rat model. Rat model studies have shown less bone loss with soya protein supplementation; 0.5 mg day genistein inhibited bone loss, but 1.6 mg genistein day showed no effect6. Genistein may act as an inhibitor of osteoclasts, which break down and absorb bone. Although positive skeletal effects of isoflavones have been demonstrated from studies in rats, there have been no peer reviewed published clinical trials of the effects of natural isoflavones on bone mass changes in humans. Published papers from such trials, on the effects of isoflavones on bone density, are anticipated in the next few years. Ipriflavone, a synthetic isoflavone derivative, has been studied extensively with regards to the prevention of osteoporosis. It appears to inhibit bone resorption i.e. helps slow bone loss, so improving bone density ipriflavone is, however, devoid of oestrogenic activity ; . These positive findings cannot be directly extrapolated to natural isoflavones found in the diet, but they should be the basis for further research, especially as daidzein one of the two principal soya isoflavones ; is one of the main metabolites of ipriflavone. Hence at present there is only tentative evidence to indicate that naturally occurring phytoestrogens have similar effects in maintaining bone density to those of the related ipriflavone, although emerging evidence suggests these substances are biologically active in experimental models. d ; Coronary Heart Disease The mortality from coronary heart disease CHD ; varies a great deal between countries. In the USA, 300 per 100, 000 men, aged 40 - 69 years, die from CHD each year. The corresponding figure in Japan is 50 per 100, 0002. The higher content of phytoestrogens in the Japanese diet has been highlighted as a potential reason for this difference. Soya has been shown to have a plasma cholesterol lowering LDL cholesterol ; effect, as effective as HRT agents. 47g soya protein day has been shown to reduce LDL cholesterol by 12.9%2. However, it must be appreciated that isolated isoflavones without soya protein have no effect on cholesterol, but they do appear to improve arterial compliance. Soya protein without isoflavones does not have a cholesterol lowering effect. Therefore the beneficial, potentially cardioprotective effect appears to be due to synergism of the components in soya, although further research is required to understand the exact mechanism of cholesterol lowering by soya proteins. The proposed mechanisms of actions involve isoflavones acting as oestrogens and exerting an antioxidant action. The protective effect of linseed may be partly due to its a- linolenic acid content.
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Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. This Italian randomized, double-blind, placebo-controlled trial assessed the effects of genistein on bone metabolism in osteopenic postmenopausal women. A total of 389 postmenopausal women with a bone mineral density BMD ; less than 0.795 g cm2 at the femoral neck and no significant comorbid conditions were included. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo n 191 ; or 54mg of genistein n 198 ; daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine change, 0.049 g cm2 [95% CI, 0.035 to 0.059] vs. 0.053 g cm2 [CI, 0.058 to 0.035]; difference, 0.10 g cm2 [CI, 0.08 to 0.12]; P 0.001 ; and the femoral neck change, 0.035 g cm2 [CI, 0.025 to 0.042] vs. 0.037 g cm2 [CI, 0.044 to 0.027]; difference, 0.062 g cm2 [CI, 0.049 to 0.073]; P 0.001 ; . Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects 19% vs. 8%; P 0.002 ; and discontinued the study.
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University of Illinois, Urbana, IL 61802, USA. ; -- Genistein injections in ovariectomized adult mice produce dose-responsive decreases in thymic weight of up to 80%. Genistein decreased thymocyte numbers up to 86% and doubled apoptosis. -- There was a corresponding reduction in splenic cells. The does that caused significant thymic and immune changes in mice was comparable to those reported in soy-fed human infants. "These results raise the possibility that serum genistein concentrations found in soy-fed infants may be capable of producing thymic and immune abnormalities, as suggested by previous reports of immune impairments in soy-fed infants." , - Also see . Frying the Brain With Soy . page 63 - short interval of consumption can significantly alter sexually dimorphic brain regions, anxiety, learning and memory . Alzheimer's disease, especially in women. - : ncbi.nlm.nih.gov entrez query.fcgi?cmd Retrieve&db PubMed&list uids 11836067&dopt Abstract . 2002 "Neurobehavioral effects of dietary soy phytoestrogens, " Lephard E.D. and others, Neurotoxicol Teratol 2002 Jan-Feb; 24 1 ; : 5-16. Neuroscience Center, 633 WIDB, Brigham Young University, Provo, UT 86402, USA. edwin lephart byu -- Male mice fed diets rich in phytoestrogens had lower levels of maze performance than male mice fed diets free of phytoestrogens. Opposite results were observed in female mice. ; -- The results indicate that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels, in many cases, over a relatively - short - interval of consumption in adulthood ; , can significantly alter sexually dimorphic brain regions, anxiety, learning and memory. -- The findings of these studies identify the biological actions of phytoestrogens, specifically isoflavones and their metabolites, found in animal soy-containing diets on brain and behavior and implicate the importance of phytoestrogens given the recognized significance of estrogens in brain and neural disorders, such as Alzheimer's disease, especially in women and lithobid.
REFERENCES 1. Knapp M. Acta Psychiatr Scand 2000; 102: 15-18. Farmer D, et al. Value in Health 7 6, Suppl. ; , P.778, 2004. Poster presented at the ISPOR 8th Annual European Congress, 6-8 November 2005, Florence, Italy.
Al-Azzawi F, Buckler HM, for the United Kingdom Vaginal Ring Investigator Group. Comparison of a novel vaginal ring delivering estradiol acetate versus oral estradiol for relief of vasomotor menopausal symptoms. Climacteric 2003; 6: 118-127. Albertazzi P Pansini F, Bonaccorsi G, Zanotti L, Forini E, Aloysio D. , The effect of dietary soy supplementation on hot flushes. Obstet Gynecol 1998; 91: 6-11. Albrecht BH, Schiff I, Tulchinsky D, Ryan KJ. Objective evidence that placebo and oral medroxyprogesterone acetate therapy diminish menopausal vasomotor flushes. J Obstet Gynecol 1981; 139: 631-635. Amato P Christophe S, Mellon PL. Estrogenic activity of herbs , commonly used as remedies for menopausal symptoms. Menopause 2002; 9: 145-150. Baber RJ, Templeman C, Morton T, Kelly GE, West L. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 1999; 2: 85-92. Barton D, Loprinzi C, Quella S, Sloan J, Pruthi S, Novotny P . Depomedroxyprogesterone acetate for hot flashes. J Pain Symptom Manage 2002; 24: 603-607. Barton DL, Loprinzi CL, Quella SK, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol 1998; 16: 495-500. Bergmans MG, Merkus JM, Corbey RS, Schellekens LA, Ubachs JM. Effect of Bellergal Retard on climacteric complaints: a double-blind, placebo-controlled study. Maturitas 1987; 9: 227-234. Blatt MHG, Wiesbader H, Kupperman HS. Vitamin E and climacteric syndrome. Arch Intern Med 1953; 91: 792-796. Boothby LA, Doering PL, Kipersztok S. Bioidentical hormone therapy: a review. Menopause 2004; 11: 356-367. Buckler H, Al-Azzawi F, for the UK VR Multicentre Trial Group. The effect of a novel vaginal ring delivering oestradiol acetate on the climacteric symptoms in postmenopausal women. Br J Obstet Gynecol 2003; 110: 753-759. Bullock JL, Massey FM, Gambrell RD Jr. Use of medroxyprogesterone acetate to prevent menopausal symptoms. Obstet Gynecol 1975; 46: 165-168. Burke GL, Legault C, Anthony M, et al. Soy protein and isoflavone effects on vasomotor symptoms in peri- and post-menopausal women: the Soy Estrogen Alternative study. Menopause 2003; 10: 147-153. Chenoy R, Hussain S, Tayob Y, et al. Effect of oral gamolenic acid from evening primrose oil on menopausal flushing. BMJ 1994; 308: 501-503. Christy CJ. Vitamin E in the menopause. J Obstet Gynecol 1945; 50: 84-87. Dalais FS, Rice GE, Wahlqvist ML, et al. Effects of dietary phytoestrogens in postmenopausal women. Climacteric 1998; 1: 124-129. Davis SR, Briganti EM, Chen RQ, Dalais FS, Bailey M, Burger HG. The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of Australian women: a randomised controlled trial. Med J Aust 2001; 174: 68-71. Faure ED, Chantre P Mares P Effects of a standardized soy extract on , . hot flushes: a multicenter, double-blind, randomized, placebocontrolled study. Menopause 2002: 9: 329-334 and lithium and isoflavone.
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F2 , and oxidized low-density lipoprotein ; at baseline and 6 wk. Analysis of variance showed that treatment had a modest effect on affecting body iron status P 0.06 ; but had no effect on oxidative stress indexes. The NP LI and NP NI treatments, respectively, reduced SF by 30% and 13% and TS by 28% and 16%. Furthermore, contrast coding NP vs. LP and NI vs. LI ; to test the effect of phytate and isoflavones revealed that only NP significantly decreased SF P 0.02 ; , SI P 0.04 ; , and TS P 0.02 ; . In conclusion, phytate-rich soy, regardless of isoflavone content, reduced body iron stores and in turn may protect against oxidative stress in aging populations. However, none of the soy treatments had a beneficial effect on oxidative stress. Additional studies with a greater number of subjects or longer duration may be needed to observe a direct effect on oxidative stress. Supported by funding from the Center for Designing Foods to Improve Nutrition, Iowa State University, and SPI from the Solae Company, St. Louis, MO. ; Effect of Isoflavone Supplementation on Lipid Profiles, Thiobarbituric AcidReactive Substances, and Nuclear Factor- B Activation in Mildly Hyperlipidemic Women. C.-Y. Choi, S.-H. Ryu, H.-Y. Cho, J.-Y. Park, J.-K. Kim, G.-S. Moon, D.-S. Kim, and Y.-S. Song. Inje University, Kimhae, Korea. Dietary intake of soy isoflavones has been associated with a decreased risk of cardiovascular disease. One possible mechanism of action is through their antioxidative effect. We found that genistein inhibits the activation of the redoxsensitive transcription factor, nuclear factor- B NF- B ; , in inflammatory macrophages in vitro. The purpose of this study is to examine the effect of isoflavone supplementation for 3 mo on the lipid profile, thiobarbituric acidreactive substances TBARS ; , and NF- B activation in mildly hyperlipidemic women. Eight women with triglyceride levels of 1.70 to 2.49 mmol L participated in this study. After signing an informed consent, subjects completed a food frequency questionnaire and took the study capsules for 3 mo. One capsule contained 100 mg of an isoflavone mixture Amax NutraSource Inc.; 13.5% daidzin, 26.3% daidzein, 38.6% genistin, 16.1% genistein, 5% glycitin, and trace amount of glycitein ; . Blood samples were collected at 0, 6, and 12 wk after isoflavone supplementation. Lipid profile, isoflavone, and TBARS levels were determined in plasma. HPLC analysis for isoflavone was conducted using a 0.46 25 cm i.d. C18 reverse-phase column ZORBAX SB C18, HP ; with a mobile phase consisting of 60: 40 v v ; methanol: ammonium acetate 1 mmol L ; at a flow rate of 1 mL min. NF- B activity was determined by an electrophoretic mobility shift assay in peripheral blood mononuclear cells PBMCs ; separated in a Ficoll gradient by centrifugation. Subjects taking isoflavone capsules had lowered triglyceride levels and suppressed NF- B activation in PBMCs; their isoflavone levels were 0.28 0.38 mol L during isoflavone supplementation. Furthermore, oxidative stress measured by TBARS was significantly lowered after 6 wk of isoflavone supplementation. None of the study subjects reported any adverse effects or unusual symptoms during or after supplementation. These results support soy isoflavone as a potent hypolipidemic agent and antioxidant that may reduce the risk of cardiovascular disease. Supported by grant NO. R012000-00187 from the Korea Science and Engineering Foundation.
Konsyl Pharmaceuticals, Inc. a leading producer of high quality, natural supplements, will be introducing a new product for the Bladder Health category in August, 2007. The new bladder control formula combines a concentrated lipid-free pumpkin seed extract with SoyLife soy germ isoflavone extract and is clinically shown to support bladder health in aging men and women.
Carrao-Panizzi, M., and K. Kitamura. 1995. Isoflavone content in Brazilian soybean cultivars. Breed. Sci. 45: 295300. Chiari, L., N.D. Piovesan, L.K. Naoe, I.C. Jose, J.M.S. Viana, M.A. Moreira, and E.G. de Barros. 2004. Genetic parameters relating isoflavone and protein content in soybean seeds. Euphytica 138: 5560. Dhaubhadel, S., B.D. McGarvey, R. Williams, and M. Gijzen. 2003. Isoflavonoid biosynthesis and accumulation in developing soybean seeds. Plant Mol. Biol. 53: 733743. Eldridge, A.C., and W.F. Kwolek. 1983. Soybean isoflavones: Effect of environment and variety on composition. J. Agric. Food Chem. 31: 394396. Environment Canada. 2002. Climate data [Online]. Available at : climate.weatheroffice.ec.gc verified 29 June 2005 ; . Environment Canada. 2004. Climate normals and averages [Online]. Available at : climate.weatheroffice.ec.gc verified 29 June 2005 ; . Fehr, W.R., C.E. Caviness, D.T. Burmond, and J.S. Pennington. 1977. Stage of development description for soybeans. Crop Sci. 11: 929 931. Graham, M.Y., and T.L. Graham. 1994. Wound-associated competency factors are required for the proximal cell responses of soybean to the Phytophthora sojae wall glucan elicitor. Plant Physiol. 105: 571578. Graham, T.L., and M.Y. Graham. 1996. Signaling in soybean phenylpropanoid responses. Plant Physiol. 110: 11231133. Graham, T.L., J.E. Kim, and M.Y. Graham. 1990. Role of constitutive isoflavone conjugates in the accumulation of glyceollin in soybean infected with Phytopthora megasperma. Mol. Plant Microbe Interact. 3: 157166. Heller, W., and G. Forkmann. 1994. Biosynthesis of flavonoids. p. 499535. In J.B. Harborne ed. ; The Flavonoids: Advances in Research Since 1986. Chapman and Hall, London, UK. Hoeck, J.A., W.R. Fehr, P.A. Murphy, and G.A. Welke. 2000. Influence of genotype and environment on isoflavone contents of soybean. Crop Sci. 40: 4851. Jackson, C.-J.C., J.P. Dini, C. Lavandier, H.P.V. Rupasinghe, H. Faulkner, V. Poysa, D. Buzzell, and S. DeGrandis. 2002. Effects of processing on the content and composition of isoflavones during manufacturing of soy beverage and tofu. Process Biochem. 37: 11171123. Jung, W., O. Yu, S.M.C. Lau, D.P. O'Keefe, J. Odell, G. Fader, and B. McGonigle. 2000. Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes. Nat. Biotechnol. 18: 208212. Kassem, M.A., K. Meksem, M.J. Iqbal, V.N. Njiti, W.J. Banz, T.A. Winters, A. Wood, and D.A. Lightfoot. 2004. Definition of soybean genomic regions that control seed phytoestrogen amounts. J. Biomed. Biotechnol. 1: 5260. Kitamura, K., K. Igita, A. Kikuchi, S. Kudou, and K. Okubo. 1991. Low isoflavone content in some early maturing cultivars, so-called summer-type soybeans Glycine max L. ; Merrill ; . Jpn. J. Breed. 41: 651654. Kosslak, R.M., R. Bookland, J. Barkei, H. Paaren, and E.R. Appelbaum. 1987. Induction of Bradyrhizobium japonicum common nod genes by isoflavones isolated from Glycine max. Proc. Natl. Acad. Sci. USA 84: 74287432. Lee, S.J., W. Yan, J.K. Ahn, and I.M. Chung. 2002. Effects of year, site, genotype and their interactions on various soybean isoflavones. Field Crops Res. 81: 181192. Manach, C., A. Scalbert, C. Morand, C. Remesy, and L. Jimenez. 2004. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 79: 727747. Meksem, K., V.N. Njiti, W.J. Banz, M.J. Iqbal, M.M. Kassem, D.L. Hyten, J. Yuang, T.A. Winters, and D.A. Lightfoot. 2001. Genomic regions that underlie soybean seed isoflavone content. J. Biomed. Biotechnol. 1 ; : 3844. Messina, J. 1999. Legumes and soybeans: Overview of their nutritional profiles and health effects. Am. J. Clin. Nutr. 70: 439450. Morris, P.F., M.E. Savard, and E.W.B. Ward. 1991. Identification and accumulation of isoflavonoids and isoflavone glucosides in soybean leaves and hypocotyls in resistance responses to Phytophthora megasperma f. sp. glycinea. Physiol. Mol. Plant Pathol. 39: 229244. Munro, I.C., M. Harwood, J.J. Hlywka, A.M. Stephen, J. Doull, W.G.
Collaborations with established third parties to manufacture and commercialize our existing and potential products. We are engaged in discussions with pharmaceutical companies regarding development of products incorporating our CDT platform and other types of marketing, manufacturing or distribution opportunities. Following is a summary of our existing collaborations. Perrigo Company. On October 20, 2005, we entered into a strategic alliance with a subsidiary of Perrigo Company. Perrigo is a leading global healthcare supplier and the world's largest manufacturer of OTC pharmaceutical and nutritional products for the store brand and contract manufacturing markets. Under the agreement, we granted a license to our CDT technology to Perrigo for the manufacture, marketing, distribution, and sale of specific dietary supplements in the United States. In addition, Perrigo may request that we develop additional dietary supplement products that use our technology to be added to the agreement. Subject to certain exceptions described in the agreement, the license we granted to Perrigo is exclusive. We will receive royalty payments based on Perrigo's net profits derived from the sales of products subject to the agreement. The first product shipments by Perrigo began in the first quarter of 2006. Wyeth Consumer Healthcare. On December 21, 2005, we entered a licensing agreement with Wyeth Consumer Healthcare, a division of Wyeth, granting Wyeth exclusive worldwide rights to use our CDT platform for the development, manufacture and commercialization of products containing ibuprofen. Wyeth is one of the world's premier consumer healthcare companies and the leading provider of ibuprofen products. Wyeth agreed to use its commercially reasonable efforts to research and develop at least one ibuprofen product for the purposes of seeking regulatory approval for the commercialization of that product and we will receive certain minimum royalty payments for this product under the agreement. We will work with Wyeth on a coordinated development program to complete the clinical development and commercialization of the initial ibuprofen product. We have the right to participate in the development of any additional products containing ibuprofen utilizing CDT technology that Wyeth seeks to advance. Wyeth paid us an initial research and development fee and agreed to pay additional fees upon the achievement of specified milestones. Wyeth also agreed to pay us a licensing fee and a technology transfer fee upon the completion of certain specified events associated with additional products containing ibuprofen. In addition, the agreement provides for quarterly royalty payments based upon a percentage of Wyeth's annual net sales of products covered by the agreement on a product-by-product basis. There are currently no extended release formulations of ibuprofen approved for use in North America. Archer Daniels Midland. On March 8, 2002, we entered into an exclusive patent license agreement with Archer Daniels Midland Company ADM ; which granted ADM an exclusive license and right of first refusal to develop and market certain dietary supplement and nutraceutical products using our CDT technology. We receive royalties based on a percentage of net sales of the licensed products. We have developed an extended release formulation for use in soy isoflavones for ADM. ADM has reported ownership of approximately 5% of our outstanding common stock. Nutraceutix. Effective as of December 31, 2003, we completed the sale of our probiotics development and manufacturing activities to Nutraceutix, Inc. The acquiring entity was established and is owned by our former vice president of operations, chief financial officer and general manager of the probiotics operations. Substantially all of the assets and properties used in connection with our probiotics sales, including equipment, inventory and intellectual property rights, were sold in this transaction. The unit engaged in the business of formulating and manufacturing probiotics-based health and dietary supplements for the animal and human nutrition markets. In connection with the sale, we granted Nutraceutix the right to manufacture and sell certain products utilizing our patented CDT technology. On August 3, 2005, we entered into a settlement and amended agreement with Nutraceutix which, among other things, restricted the license granted to Nutraceutix to use our CDT technology for sales to a limited number of designated customers. The settlement provided for Nutraceutix to pay us royalties on the sale of products incorporating CDT technology at a reduced rate from July 2005, until termination of its license on December 31, 2007, subject to extension for an additional year under certain circumstances. 5.
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