• 1
    Epstein CJ. (1995) Down syndrome (trisomy 21). In: ScriverCR, BeaudetAL, SlyWS, ValleD, editors. The Metabolic and Molecular Bases of Inherited Disease Volume 1. New York : McGrawHill. p 74994.
  • 2
    Marder E, Dennis J. (1997) Medical management of children with Down's syndrome. Current Paediatrics 7: 17.
  • 3
    Halliwell B, Gutteridge JMC. (1989) Free Radicals in Biology and Medicine. 2nd edn. Oxford : Clarendon Press.
  • 4
    Kedziora J, Bartosz G. (1988) Down's syndrome: a pathology involving the lack of balance of reactive oxygen species. Free Radical Biology and Medicine 4: 31730.
  • 5
    Peled-Kamar M, Lotem J, Okon E, Sachs L, Groner Y. (1995) Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome. EMBO Journal 14: 498593.
  • 6
    Sinet PM. (1982) Metabolism of oxygen derivatives in Downs syndrome. In: SinexFM, MerrilCR editors. Alzheimer's Disease, Downs Syndrome and Ageing. New York : The New York Academy of Sciences. p8394.
  • 7
    Sinet PM, Lejeune J, Jerome H. (1979) Trisomy 21 (Down's syndrome). Glutathione peroxidase, hexose monophoshate shunt and IQ. Life Sciences 24: 2933.
  • 8
    Sinet PM, Lavelle F, Michelson AM, Jerome H. (1975) Superoxide dismutase activities of blood platelets in trisomy 21. Biochemical and Biophysical Research Communications 67: 9049.
  • 9
    Crosti N, Serra A, Rigo A, Viglino P. (1976) Dosage effect of SOD-A gene in 21-trisomic cells. Human Genetics 31: 197202.
  • 10
    Feaster WW, Kwok KW, Epstein CJ. (1977) Dosage effects for superoxide dismutase-1 in nucleated cells anueploid for chromosome 21. American Journal of Human Genetics 29: 56370.
  • 11
    Bjorksten B, Marklund S, Hagglof B. (1984) Enzymes of leukocyte oxidative metabolism in Down's syndrome. Acta Paediatrica Scandinavica 73: 97101.
  • 12
    Brooksbank BW, Balazs R. (1984) Superoxide dismutase, glutathione peroxidase and lipid peroxidation in Down's syndrome fetal brain. Brain Research 318: 3744.
  • 13
    Kedziora J, Bartosz G, Gromadzinska J, Sklodowska M, Wesowicz W, Scianowski J. (1986) Lipid peroxides in blood plasma and enzymatic antioxidative defence of erythrocytes in Down's syndrome. Clinica Chimica Acta 154: 1914.
  • 14
    Tanabe T, Kawamura N, Morinobu T, Murata T, Tamai H, Mino M, Takai T. (1994) Antioxidant enzymes and vitamins in Down's syndrome. Pathophysiology 1: 937.
  • 15
    De-la-Torre R, Casado A, Lopez-Fernandez E, Carrascosa D, Ramirez V, Saez J. (1996) Overexpression of copper-zinc superoxide dismutase in trisomy 21. Experientia 52: 8713.
  • 16
    Pastor MC, Sierra C, Dolade M, Navarro E, Brandi N, Cabre E, Mira A, Seres A. (1998) Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome patients. Clinical Chemistry 44: 9249.
  • 17
    Ceballos-Picot I, Nicole A, Briand P, Grimber G, Delacourte A, Defossez A, Javoy-Agid F, Lafon M, Blouin J, Sinet PM. (1991) Neuronal-specific expression of human copper-zinc superoxide dismutase gene in transgenic mice: animal model of gene dosage effects in Down's syndrome. Brain Research 552: 198214.
  • 18
    Ceballos I, Delabar JM, Nicole A, Lynch RE, Hallewell RA, Kamoun P, Sinet PM. (1988) Expression of transfected human CuZn superoxide dismutase gene in mouse L cells and NS20Y neuroblastoma cells induces enhancement of glutathione peroxidase activity. Biochimica et Biophysica Acta Gene Structure and Expression 949: 5864.
  • 19
    Barkats M, Bertholet JY, Venault P, Ceballos-Picot I, Nicole A, Phillips J, Moutier R, Roubertoux P, Sinet PM, Cohen-Salmon C. (1993) Hippocampal mossy fiber changes in mice transgenic for the human copper-zinc superoxide dismutase gene. Neuroscience Letters 160: 248.
  • 20
    Nabarra B, Casanova M, Paris D, Nicole A, Toyama K, Sinet PM, Ceballos I, London J. (1996) Transgenic mice overexpressing the human Cu/Zn-SOD gene: ultrastructural studies of a premature thymic involution model of Down's syndrome (trisomy 21). Laboratory Investigation 74: 61726.
  • 21
    Elroy-Stein O, Bernstein Y, Groner Y. (1986) Overproduction of human Cu/Zn-superoxide dismutase in transfected cells: extenuation of paraquat-mediated cytotoxicity and enhancement of lipid peroxidation. EMBO Journal 5: 61522.
  • 22
    Ceballos-Picot I, Nicole A, Clement M, Bourre JM, Sinet PM. (1992) Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase. Mutation Research 275: 28193.
  • 23
    Mirochnitchenko O, Inouye M. (1996) Effect of overexpression of human Cu Zn superoxide dismutase in transgenic mice on macrophage functions. Journal of Immunology 156: 157886.
  • 24
    Busciglio J, Yankner BA. (1995) Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. Nature 378: 7769.
  • 25
    Shah SN, Johnson RC, Singh VN. (1989) Antioxidant vitamin (A and E) status of Down's syndrome subjects. Nutrition Research 9: 70915.
  • 26
    Bras A, Monteiro C, Rueff J. (1989) Oxidative stress in trisomy 21. A possible role in cataractogenesis. Ophthalmic Paediatrics Genetics 10: 2717.
  • 27
    Jovanovic SV, Clements D, MacLeod K. (1998) Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Radical Biology and Medicine 25: 10448.
  • 28
    Sinet PM, Michelson AM, Bazin A, Lejeune J, Jerome H. (1975b) Increase in glutathione peroxidase activity in erythrocytes from trisomy 21 subjects. Biochemical and Biophysical Research Communications 67: 91015.
  • 29
    Agar NS, Hingston J. (1980) Glutathione peroxidase activity in red blood cells from subjects with Down's syndrome and non-mongoloid mental retardation. Medical Journal of Australia 1: 5567.
  • 30
    Kedziora J, Lukaszewicz R, Koter M, Bartosz G, Pawlowska B, Aitkin D. (1982) Red blood cell glutathione peroxidase in simple trisomy 21 and translocation 21/22. Experientia 38: 5434.
  • 31
    Neve J, Sinet PM, Molle L, Nicole A. (1983) Selenium, zinc and copper in Down's syndrome (trisomy 21): blood levels and relations with glutathione peroxidase and superoxide dismutase. Clinica Chimica Acta 133: 20914.
  • 32
    Neve J, Vertongen F, Cauchie P, Gnat D, Molle L. (1984) Selenium and glutathione peroxidase in plasma and erythrocytes of Down's syndrome (Trisomy 21) patients. Journal of Mental Deficiency Research 28: 2618.
  • 33
    Gromadzinska J, Wasowicz W, Sklodowska M. (1988) Glutathione peroxidase activity, lipid peroxides and selenium status in blood in patients with Down's syndrome. Journal of Clinical Chemistry and Clinical Biochemistry 26: 2558.
  • 34
    Wijnen LMM, Monteba-Van Heuvel M, Pearson PL, Meera Khan P. (1978) Assignment of a gene for glutathione peroxidase (GPX1) to human chromosome 3. Cytogenetics and Cell Genetics 22: 2325.
  • 35
    de Haan JB, Wolvetang EJ, Iannello R, Bladier C, Keiner MJ, Kola I. (1997) Reactive oxygen species and their contribution to pathology in Downs syndrome. Advances in Pharmacology 38: 379402.
  • 36
    Anneren G, Bjorksten B. (1984) Low superoxide levels in blood phagocytic cells in Down's syndrome. Acta Paediatrica Scandinavica 73: 3458.
  • 37
    Mills EL, Quie- PG. (1980) Congenital disorders of the function of polymorphonuclear neutrophils. Reviews of Infectious Diseases 2: 50517.
  • 38
    Baehner RL. (1996) Chronic granulomatous disease. In: BehrmanRE, KliegmanRM, ArvinAM, editors. Nelson Textbook of Pediatrics. Philadelphia : WB Saunders Company. p 5968.
  • 39
    Kedziora J, Blaszczyk J, Sibinska E, Bartosz G. (1990) Down's syndrome: increased enzymatic antioxidative defence is accompanied by decreased superoxide anion generation in blood. Hereditas 113: 735.
  • 40
    Pincheira J, Navarrete MH, de la Torre C, Santos MJ. (1999) Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Downs syndrome. Clinical Genetics 55: 1927.
  • 41
    Sano M, Ernesto C, Thomas RG, Klauber MR, Schaffer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, et al. (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. New England Journal of Medicine 336: 121622.
  • 42
    Milunsky A, Hackley BM, Halsted JA. (1970) Plasma, erythrocyte and leucocyte zinc levels in Down's syndrome. Journal of Mental Deficiency Research 14: 99105.
  • 43
    Bjorksten B, Back O, Gustavson KH, Hallmans G, Hagglof B, Tarnvik A. (1980) Zinc and immune function in Down's syndrome. Acta Paediatrica Scandinavica 69: 1837.
  • 44
    Fabris N, Amadio L, Licastro F, Mocchegiani E, Zannotti M, Francheschi C. (1984) Thymic hormone deficiency in normal ageing and Down's syndrome: is there a primary failure of the thymus? Lancet 1: 9836.
  • 45
    Franceschi C, Chiricolo M, Licastro F, Zannotti M, Masi M, Mocchegiani E, Fabris N. (1988) Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects. Journal of Mental Deficiency Research 32: 16981.
  • 46
    Purice M, Maximilian C, Dumitriu I, Ioan D. (1988) Zinc and copper in plasma and erythrocytes of Down's syndrome children. Endocrinologie 26: 11317.
  • 47
    Stabile A, Pesaresi MA, Stabile AM, Pastore M, Sopo SM, Ricci R, Celestini E, Segni G. (1991) Immunodeficiency and plasma zinc levels in children with Down's syndrome: a long-term follow-up of oral zinc supplementation. Clinical Immunology and Immunopathology 58: 20716.
  • 48
    Rascon Trincado MV, Lorente Toledano F, Salazar A-Villalobos V. (1992) Evaluation of plasma zinc levels in patients with Down syndrome. Anales Espanoles De Pediatria 37: 3913.
  • 49
    Licastro F, Mocchegiani E, Zannotti M, Arena G, Masi M, Fabris N. (1992) Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. International Journal of Neuroscience 65: 25968.
  • 50
    Licastro F, Mocchegiani E, Masi M, Fabris N. (1993) Modulation of the neuroendocrine system and immune functions by zinc supplementation in children with Down's syndrome. Journal of Trace Element and Electrolytes in Health and Disease 7: 2379.
  • 51
    Licastro F, Chiricolo M, Mocchegiani E, Fabris N, Zannoti M, Beltrandi E, Mancini R, Parente R, Arena G, Masi M. (1994) Oral zinc supplementation in Down's syndrome subjects decreased infections and normalized some humoral and cellular immune parameters. Journal of Intellectual Disability Research 38: 14962.
  • 52
    Sustrova M, Strbak V. (1994) Thyroid function and plasma immunoglobulins in subjects with Down's syndrome (DS) during ontogenesis and zinc therapy. Journal of Endocrinological Investigation 17: 38590.
  • 53
    Brigino EN, Good RA, Koutsonikolis A, Day NK, Kornfeld SJ. (1996) Normalization of cellular zinc levels in patients with Down's syndrome does not always correct low thymulin levels. Acta Paediatrica 85: 13702.
  • 54
    Kadrabova J, Madaric A, Sustrova M, Ginter E. (1996) Changed serum trace element profile in Down's syndrome. Biological Trace Element Research 4: 2016.
  • 55
    McBean LD, Smith JC, Berne BH, Halsted JA. (1974) Serum zinc and alpha2-macroglobulin concentration in myocardial infarction, decubitus ulcer, multiple myeloma, prostatic carcinoma, Down's syndrome and nephrotic syndrome. Clinica Chimica Acta 50: 4351.
  • 56
    Matin MA, Sylvester PE, Edwards D, Dickerson JWT. (1981) Vitamin and zinc status in Down's syndrome. Journal of Mental Deficiency Research 25: 1216.
  • 57
    Yarom R, Sherman Y, Sagher U, Peled IJ, Wexler MR, Gorodetsky R. (1987) Elevated concentrations of elements and abnormalities of neuromuscular junctions in tongue muscles of Down's syndrome. Journal of the Neurological Sciences 79: 31526.
  • 58
    Lockitch G, Puterman M, Godolphin W, Sheps S, Tingle AJ, Quigley G. (1989) Infection and immunity in Down's syndrome: a trial of long-term low oral doses of zinc. Journal of Pediatrics 114: 7817.
  • 59
    Chiricolo M, Musa AR, Monti D, Zannotti M, Franceschi C. (1993) Enhanced DNA repair in lymphocytes of Down's syndrome patients: the influence of zinc nutritional supplementation. Mutation Research 295: 10511.
  • 60
    Anneren G, Magnusson CG, Nordvall SL. (1990) Increase in serum concentrations of IgG2 and IgG4 by selenium supplementation in children with Down's syndrome. Archives of Disease in Childhood 65: 13535.
  • 61
    Antila E, Nordberg U, Syväoja E, Westermarck T. (1990) Selenium therapy in Down Syndrome: a theory and a clinical trial. Advances in Experimental Medicine and Biology 264: 1836.
  • 62
    Harrell RF, Capp RH, Davis DR, Peerless J, Ravitz LR. (1981) Can nutritional supplements help mentally retarded children? An exploratory study. Proceedings of the National Academy of Sciences USA. 78: 5748.
  • 63
    Bennett FC, McClelland S, Kriegsmann EA, Andrus LB, Sells CJ. (1983) Vitamin and mineral supplementation in Down's syndrome. Pediatrics 72: 70713.
  • 64
    Coburn SP, Schaltenbrand WE, Mahuren DJ, Clausman RJ, Townsend D. (1983) Effect of megavitamin treatment on mental performance and plasma vitamin B6 concentrations in mentally retarded young adults. American Journal of Clinical Nutrition 38: 3525.
  • 65
    Ellis NR, Tomporowski PD. (1983) Vitamin/mineral supplements and intelligence of institutionalized mentally retarded adults. American Journal of Mental Deficiency 88: 21114.
  • 66
    Smith GF, Spiker D, Cicchetti D, Justice E. (1983) Failure of vitamin/mineral supplementation in Down's syndrome. Lancet 2: 41. (Letter.).
  • 67
    Weathers C. (1983) Effects of nutritional supplementation on IQ and certain other variables associated with Down's syndrome. American Journal of Mental Deficiency 88: 21417.
  • 68
    Bidder RT, Gray P, Newcombe RG, Evans BK, Hughes M. (1989) The effects of multivitamins and minerals on children with Down's syndrome. Developmental Medicine & Child Neurology 31: 5327.
  • 69
    Palmer S. (1978) Influence of vitamin A nutriture on the immune response: findings in children with Down's syndrome. International Journal of Vitamin and Nutrition Research 48: 188216.
  • 70
    Pueschel SM, Hillemeier C, Caldwell M, Senft K, Mevs C, Pezzullo JC. (1990) Vitamin A gastrointestinal absorption in persons with Down's syndrome. Journal of Mental Deficiency Research 34: 26975.
  • 71
    Barden HS. (1977) Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome. Journal of Mental Deficiency Research 21: 6374.
  • 72
    Storm W. (1990) Hypercarotenaemia in children with Down's syndrome. Journal of Mental Deficiency Research 34: 2836.
  • 73
    Cutress TW, Mickleson KN, Brown RH. (1976) Vitamin A absorption and periodontal disease in trisomy G. Journal of Mental Deficiency Research 20: 1723.
  • 74
    Coleman M, Sobel S, Bhagavan HN, Coursin D, Marquardt A, Guay M, Hunt C. (1985) A double blind study of vitamin B6 in Down's syndrome infants. Part 1 - Clinical and biochemical results. Journal of Mental Deficiency Research 29: 23340.
  • 75
    Tu J, Zellweger H. (1965) Blood-serotonin deficiency in Down's syndrome. Lancet 2: 71517.
  • 76
    Bazelon M, Paine RS, Cowie VA, Hunt P, Houck JC, Mahanand D. (1967) Reversal of hypotonia in infants with Down's syndrome by administration of 5-hydroxytryptophan. Lancet 1: 11303.
  • 77
    Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M. (1987) Alzheimer-like neurotransmitter deficits in adult Down's syndrome brain tissue. Journal of Neurology, Neurosurgery and Psychiatry 50: 7758.
  • 78
    Petre-Quadens O, De Lee C. (1975) 5-Hydroxytryptophan and sleep in Down's syndrome. Journal of the Neurological Sciences 26: 44353.
  • 79
    Pueschel SM, Reed RB, Cronk CE, Goldstein BI. (1980) 5-hydroxytryptophan and pyridoxine. The effects in young children with Down's syndrome. American Journal of Diseases of Children 134: 83844.
  • 80
    Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. (1998) Vitamin C exhibitspro-oxidant properties. Nature 392: 559. (Letter.).
  • 81
    Rigter H, Crabbe JC. (1979) Modulation of memory by pituitary hormones and related peptides. Vitamins and Hormones 37: 153241.
  • 82
    Eisenberg J, Hamburger-Bar R, Belmaker RH. (1984) The effect of vasopressin treatment on learning in Down's syndrome. Journal of Neural Transmission 60: 1437.
  • 83
    Bumbalo TS, Morelewicz HV, Berens DL, Buffalo MD. (1964) Treatment of Down's syndrome with the “U” series of drugs. Journal of American Medical Association 187: 361.
  • 84
    Turkel H, Nusbaum I. (1985) Medical Treatment of Down Syndrome and Genetic Diseases. 4th edn. Southfield , Michigan : Ubiotica.
  • 85
    Kirkwood BR. (1988) Essentials of Medical Statistics. London : Blackwell Science.
  • 86
    Wisniewski KE, Kida E, Ted Brown W. (1996) Consequences of genetic abnormalities in Down's syndrome on brain structure and function. In: RondalJA, PereraJ, NadelL, ComblainA, editors. Down's Syndrome. Psychological, Psychobiological, and Socio-educational Perspectives. London : Whurr Publishers Ltd. p 319.