《china--milk》ppt课件.ppt
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1、ANTIOXIDANT PROPERTIES OF THE HUMAN MILK,Giuseppe Buonocore University of Siena,University of Siena,EURAIBI Int. Foundation,Neobrain network,Fetal life is sustained under low oxygen tension; however, as breathing begins immediately after birth, a rapid increase in tissue oxygenation takes place,Oxyg
2、en,essential to life,but,potentially,toxic,Oxygen is potentially toxic, because of the production of Reactive Oxygen Species (Free Radicals),Any species capable of independent existence that contains one or more unpaired electrons in outer orbital,Carbon-centered,Free Radicals,(3O2) Singlet state (1
3、O2) Superoxide anion (O2-) Hydroxyl radical (OH) Nitric Oxide (NO) Peroxynitrite (ONOO-) Hypoclorous acid (HOCl) Hydrogen peroxide (H2O2) Alkoxyl radical (LO) Peroxyl radical (LO2),Oxygen-centered,Hydrogen-centered,Sulfur-centered,Nitrogen-centered,(CCl3),(H),( R-S),Phenyl diazine radical,Free Radic
4、als Generation,FREE RADICAL DAMAGE,Buonocore G, Acta Pediatr 2002,Hyperoxia,Hypoxia,Ischemia- reperfusion,Free iron,Phagocyte activaction,Nitric Oxide,Arachidonic acid cascade,The antioxidant defense system matures during gestation to face this physiologic situation,Frank L, Groseclose EE. Pediatr R
5、es 1984,ANTIOXIDANT DEFENCES IN THE NEWBORN,GSH-Px Activity SOD - Carotene Riboflavin Transferrin Caeruloplasmin,- Proteinase Vit. E Selenium Copper Zinc Other plasma factors,Buonocore G, Acta Pediatr 2002,Metabolic pathways for the generation of reactive oxygen and nitrogen species in the cell (Buo
6、nocore 2007 Semin Fetal Neonatal Med),ROS/RNS,Antioxidants,“Describes various deleterious processes resulting from an imbalance between excessive formation of free radicals derived from an incomplete oxygen or nitrogen reduction and antioxidant defences.”,Oxidative Stress,Helmut Sies 1991,Oxygen, in
7、flammation, Isch-Rep, Free Iron, Arachidonic acid cascade,Anti- oxidant factors,Pro-oxidative factors,SOD, Catalase, Glutathione Peroxidase, Glutathione, Bilirubin, Ascorbic acid, Tocopherol, Uric acid, etc,Oxidative Stress,High in the newborn,Low in the preterm,Oxidative stress in the preterm infan
8、t,Lower intracellular antioxidative defence Susceptibility to infections/inflammation Free iron in plasma Exposition to high oxygen concentration,Hyperoxia Duration of oxygen therapy Hypoxia Alternating hypoxia and hyperoxia The range of PO2 variation Hypercapnea Hypocapnea Fluctuations of pCO2 Meta
9、bolic acidosis Metabolic alkalosis Recurrent apnea Bronchopulmonary dysplasia Intraventricular hemorrhage Exposure to bright light,CLINICAL CONDITIONS AND RISK FACTORS ASSOCIATED WITH FR DISEASE OF THE NEWBORN,Periventricular leucomalacia Intrauterine growth retardation Septicemia Circulatory instab
10、ility Vitamin E deficiency High free iron status Mechanical ventilation Surfactant administration Blood transfusions Indomethacin administration Methyl-xanthine administration Intravenous lipid administration Dexamethasone therapy Maternal bleeding Maternal use of betablockers,Oxidative hemolysis,Re
11、nal failure,Retinopathy of prematurity,Brain damage,Cronic lung disease,Necrotizing enterocholitis,FR,FREE RADICALS DISEASE OF THE NEWBORN,TIME RELATED FREE RADICALS DISEASES,NEC,RETINOPATHY,BPD,23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Wks,JAUNDICE,BRAIN DAMAGE,RENAL FAILURE,Percent of
12、COHb in jaundiced and non-jaundiced neonates,Buonocore G, Biol Neonate 1983,Bracci R. et al, Acta Paediatr Scand 1988,GSH-Px SOD CAT,5 10 15,274 205 137 68,r =- 0.24 P0.01,r =- 0.36 P0.01,IU/gHb,U/mgHb,U/ 0.1mgHb,At birth,After 4 days of life,Peak bilirubin levels,5 10 15,5 10 15,r =- 0.31 P0.05,r =
13、- 0.35 P0.01,NS,NS,PRETERM BABIES,15 12 9 6 3 0,p = 0.0001,Plasma Free Iron (mmol/l),Normoxic,Hypoxic,Plasma Free Iron (mmol/l),TERM BABIES,15 12 9 6 3 0,*,*,p 0.001,Buonocore G et al., Free Rad Biol Med 2002,Hb Auto-oxidation Drugs metabolism,.O2-,H2O2,Fe redox,.O2- OH,H2O2,Protein denaturation Lip
14、id peroxidation,MetHb,Inactivation of Ca2+Mg2+ATPasi GSH recycling Vit E recycling,Phagocytosis Ischemia and Reperfusion Hyperoxygenation Endotelial reaction Drugs metabolism Hypoxia,Antioxidant power,Oxidative hemolysis,Extra-red cell source of RL,Intra-red cell source of RL,Strategies to minimize
15、the risk of peroxidation and protect the baby from oxidative stress,Goal: Promoting his antioxidant defenses,Human milk has been considered as a package of essential nutrients (vitamins, minerals, essential aminoacids and fatty acids) and is commonly known as the best kind of nutrition for neonates
16、and infants for the first six months of life.,An increasing body of evidence documents the protective effects of breast milk against various infectious diseases in infants including: respiratory infections diarrhea otitis media, infections in premature infants,Lonnerdal B. , Nutrition. 2000; Lawrenc
17、e R.M. Curr. Probl. Pediatr. Adolesc. Health Care. 2007;,In addition human milk has bioactive components that protect newborns from a hyperoxic challenge due to transition of life to an environment far richer in oxygen than intrauterine environment.,Buonocore G. 2000, Buonocore g. 2002 Saugstad O.D.
18、 2003; Friel J.K., Pediatr. Res. 2004;56:878882.,In addition to providing nutritional, gastrointestinal, immunological, and developmental benefits, there is good evidence that BM has antioxidant properties. Antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase, in
19、 BM are believed to assist the destruction of H2O2 and other ROS . Furthermore, scavengers of free radicals, including a-tocopherol, cysteine, and ascorbic acid are also present in human BM, and at concentrations considerably higher than in cows milk .,Callen J, Adv Neonal Care, 2005 Shoji H, J Pedi
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