《china--milk》ppt课件
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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
5 10 15
5 10 15
5 10 15
GSH-Px
SOD
CAT
At birth
After 4 days of life Bracci R. et al, Acta Paediatr Scand 1988
Plasma Free Iron (mmol/l)
p = 0.0001 15
12
*
9
6
3
0 PRETERM BABIES
1. Lonnerdal B. , Nutrition. 2000; 2. Lawrence R.M. Curr. Probl. Pediatr. Adolesc. Health Care. 2007;
CLINICAL CONDITIONS AND RISK FACTORS ASSOCIATED WITH FR DISEASE OF THE NEWBORN
• Hyperoxia • Duration of oxygen therapy • Hypoxia • Alternating hypoxia and hyperoxia • The range of PO2 variation • Hypercapnea • Hypocapnea • Fluctuations of pCO2 • Metabolic acidosis • Metabolic alkalosis • Recurrent apnea • Bronchopulmonary dysplasia • Intraventricular hemorrhage • Exposure to bright light
Oxidative stress in the preterm infant
• Lower intracellular antioxidative defence • Susceptibility to infections/inflammation • Free iron in plasma • Exposition to high oxygen concentration
TIME RELATED FREE RADICALS DISEASES
RETINOPATHY BPD
JAUNDICE
NEC
BRAIN DAMAGE
RENAL FAILURE 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Wks
Percent of COHb in jaundiced and non-jaundiced
FREE RADICALS DISEASE OF THE NEWBORN
Necrotizing enterocholitis
Cronic lung disease
FR
Oxidative hemolysis
Brain damage
Retinopathy of prematurity
Renal failure
• Ischemia and Reperfusion
Intra-red cell source of RL
• Hb Auto-oxidation
• Drug’s metabolism
• Hyperoxygenation • Endotelial reaction • Drug’s metabolism • Hypoxia
.O2-
Fe
H2O2 redox
Antioxidant power
MetHb
Protein denaturation Lipid peroxidation
.O2-
H2O2
Inactivation of
OH
Ca2+Mg2+ATPasi GSH recycling
Vit E recycling
Oxidative hemolysis
Buonocore G et al., Free Rad Biol Med 2002
Hypoxic
Normoxic
15
12
9
*
p < 0.001
6
3
0 TERM BABIES
Plasma Free Iron (mmol/l)
Extra-red cell source of RL
• Phagocytosis
GSH-Px Activity SOD - Carotene Riboflavin Transferrin Caeruloplasmin
- Proteinase Vit. E Selenium Copper Zinc Other plasma factors
Buo
electrons in outer orbital
Free Radicals
Oxygen-centered
✓ (3O2)
✓ Singlet state (1O2) ✓ Superoxide anion (O2•-) ✓ Hydroxyl radical (•OH) ✓ Nitric Oxide (NO•) ✓ Peroxynitrite (ONOO-) ✓ Hypoclorous acid (HOCl)
✓ Hydrogen peroxide (H2O2) ✓ Alkoxyl radical (LO•) ✓ Peroxyl radical (LO2•)
Carbon-centered Hydrogen-centered Sulfur-centered Nitrogen-centered
✓ (CCl3•) ✓ (H•) ✓ ( R-S•) ✓ Phenyl diazine radical
Metabolic pathways for the generation of reactive oxygen and nitrogen species in the cell (Buonocore 2007 Semin Fetal Neonatal Med)
Oxidative Stress
“Describes various deleterious processes resulting from an imbalance between excessive formation of free radicals derived from an
High in the newborn
Anti- oxidant factors
Low in the preterm
Oxidative Stress
SOD, Catalase, Glutathione Peroxidase, Glutathione, Bilirubin, Ascorbic acid, Tocopherol, Uric acid, etc
Free iron
The antioxidant defense system matures during gestation to face this physiologic situation
Frank L, Groseclose EE. Pediatr Res 1984
ANTIOXIDANT DEFENCES IN THE NEWBORN
incomplete oxygen or nitrogen reduction and antioxidant defences.”
ROS/RNS
Antioxidants
Helmut Sies 1991
Pro-oxidative factors
Oxygen, inflammation, Isch-Rep, Free Iron, Arachidonic acid cascade
ANTIOXIDANT PROPERTIES OF THE HUMAN MILK
Giuseppe Buonocore
University of Siena
EURAIBI Int. Foundation
University of Siena
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
Free Radicals Generation
Hypoxia
Arachidonic acid cascade
Nitric Oxide
FREE RADICAL DAMAGE
Hyperoxia
Ischemiareperfusion
Buonocore G, Acta Pediatr 2002
Phagocyte activaction
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
neonates
Buonocore G, Biol Neonate 1983
274
IU/gHb
U/mgHb
U/ 0.1mgHb
Peak bilirubin levels
205 r =- 0.24
P<0.01
NS r =- 0.35
P<0.01
137
NS
r =- 0.36 P<0.01 68
r =- 0.31 P<0.05
• Periventricular leucomalacia • Intrauterine growth retardation • Septicemia • Circulatory instability • 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
Visualization by confocal laser-scanning fluorescence microscopy of autologous IgG binding to erythrocytes incubated aerobically
Buonocore et al., Free Radical Biology and Medicine, 2002
Strategies to minimize 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 and infants for the first
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
5 10 15
5 10 15
5 10 15
GSH-Px
SOD
CAT
At birth
After 4 days of life Bracci R. et al, Acta Paediatr Scand 1988
Plasma Free Iron (mmol/l)
p = 0.0001 15
12
*
9
6
3
0 PRETERM BABIES
1. Lonnerdal B. , Nutrition. 2000; 2. Lawrence R.M. Curr. Probl. Pediatr. Adolesc. Health Care. 2007;
CLINICAL CONDITIONS AND RISK FACTORS ASSOCIATED WITH FR DISEASE OF THE NEWBORN
• Hyperoxia • Duration of oxygen therapy • Hypoxia • Alternating hypoxia and hyperoxia • The range of PO2 variation • Hypercapnea • Hypocapnea • Fluctuations of pCO2 • Metabolic acidosis • Metabolic alkalosis • Recurrent apnea • Bronchopulmonary dysplasia • Intraventricular hemorrhage • Exposure to bright light
Oxidative stress in the preterm infant
• Lower intracellular antioxidative defence • Susceptibility to infections/inflammation • Free iron in plasma • Exposition to high oxygen concentration
TIME RELATED FREE RADICALS DISEASES
RETINOPATHY BPD
JAUNDICE
NEC
BRAIN DAMAGE
RENAL FAILURE 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Wks
Percent of COHb in jaundiced and non-jaundiced
FREE RADICALS DISEASE OF THE NEWBORN
Necrotizing enterocholitis
Cronic lung disease
FR
Oxidative hemolysis
Brain damage
Retinopathy of prematurity
Renal failure
• Ischemia and Reperfusion
Intra-red cell source of RL
• Hb Auto-oxidation
• Drug’s metabolism
• Hyperoxygenation • Endotelial reaction • Drug’s metabolism • Hypoxia
.O2-
Fe
H2O2 redox
Antioxidant power
MetHb
Protein denaturation Lipid peroxidation
.O2-
H2O2
Inactivation of
OH
Ca2+Mg2+ATPasi GSH recycling
Vit E recycling
Oxidative hemolysis
Buonocore G et al., Free Rad Biol Med 2002
Hypoxic
Normoxic
15
12
9
*
p < 0.001
6
3
0 TERM BABIES
Plasma Free Iron (mmol/l)
Extra-red cell source of RL
• Phagocytosis
GSH-Px Activity SOD - Carotene Riboflavin Transferrin Caeruloplasmin
- Proteinase Vit. E Selenium Copper Zinc Other plasma factors
Buo
electrons in outer orbital
Free Radicals
Oxygen-centered
✓ (3O2)
✓ Singlet state (1O2) ✓ Superoxide anion (O2•-) ✓ Hydroxyl radical (•OH) ✓ Nitric Oxide (NO•) ✓ Peroxynitrite (ONOO-) ✓ Hypoclorous acid (HOCl)
✓ Hydrogen peroxide (H2O2) ✓ Alkoxyl radical (LO•) ✓ Peroxyl radical (LO2•)
Carbon-centered Hydrogen-centered Sulfur-centered Nitrogen-centered
✓ (CCl3•) ✓ (H•) ✓ ( R-S•) ✓ Phenyl diazine radical
Metabolic pathways for the generation of reactive oxygen and nitrogen species in the cell (Buonocore 2007 Semin Fetal Neonatal Med)
Oxidative Stress
“Describes various deleterious processes resulting from an imbalance between excessive formation of free radicals derived from an
High in the newborn
Anti- oxidant factors
Low in the preterm
Oxidative Stress
SOD, Catalase, Glutathione Peroxidase, Glutathione, Bilirubin, Ascorbic acid, Tocopherol, Uric acid, etc
Free iron
The antioxidant defense system matures during gestation to face this physiologic situation
Frank L, Groseclose EE. Pediatr Res 1984
ANTIOXIDANT DEFENCES IN THE NEWBORN
incomplete oxygen or nitrogen reduction and antioxidant defences.”
ROS/RNS
Antioxidants
Helmut Sies 1991
Pro-oxidative factors
Oxygen, inflammation, Isch-Rep, Free Iron, Arachidonic acid cascade
ANTIOXIDANT PROPERTIES OF THE HUMAN MILK
Giuseppe Buonocore
University of Siena
EURAIBI Int. Foundation
University of Siena
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
Free Radicals Generation
Hypoxia
Arachidonic acid cascade
Nitric Oxide
FREE RADICAL DAMAGE
Hyperoxia
Ischemiareperfusion
Buonocore G, Acta Pediatr 2002
Phagocyte activaction
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
neonates
Buonocore G, Biol Neonate 1983
274
IU/gHb
U/mgHb
U/ 0.1mgHb
Peak bilirubin levels
205 r =- 0.24
P<0.01
NS r =- 0.35
P<0.01
137
NS
r =- 0.36 P<0.01 68
r =- 0.31 P<0.05
• Periventricular leucomalacia • Intrauterine growth retardation • Septicemia • Circulatory instability • 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
Visualization by confocal laser-scanning fluorescence microscopy of autologous IgG binding to erythrocytes incubated aerobically
Buonocore et al., Free Radical Biology and Medicine, 2002
Strategies to minimize 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 and infants for the first