1. Musculoskeletal Group Case #1 4/21/08 Brian Caserto

2. Lesion Cause Relationship Pig 1 Massive/ Centrilobular Hepatic Necrosis Vit E/ Selenium Deficiency  increased free rad  oxidative necrosis Vit E- Cell membranes  Free radical scavenger Selenium  Cytosol  free radical scavenger Pig 2 Gastric Ulcer Microangiopathy Induced by Vit E Selenium def Local ischemia  infarciton  necrosis and ulceration Epicardial Hemorrhage Microangiopathy Vessel damage  hemorrhage Both Pigs Skeletal muscle necrosis and calcification Vit E Sel Def  cell membrane damage  decreased Mitochondrial ATP ER cant sequester Ca++  Hypercontraction  myofiber coagulation

3. Oxidative cell injury and necrosis Antioxidant deficiency Increased Cellular free radicals Cell membrane damage Mitochondrial membrane damage Vitamin E Vitamin E Selenium- Glutathione peroxidase Mitochondria

4. Liver Affected Tissues Blood Vessels Skeletal Muscle Necrosis Ischemia and infarction Hemorrhage Myocyte degeneration and calcification Thrombosis Necrosis

5. Vitamin E Selenium Membrane protectors Cytosol protectors Cellular Defense against oxidant injury Free Radicals: Superoxide anion Hydrogen peroxide Hydroxyl radical Glutathione peroxidase: 2GSH + H 2 O 2 -> GS–SG + 2H 2 O Glutathione reductase: GS–SG + NADPH + H + -> 2 GSH + NADP + .

6. Vitamin E- Alpha Tocopherol Vitamin C- Ascorbic Acid

8. Liver: Massive to centrilobular necrosis

9. Liver: Massive to centrilobular necrosis

10. Liver: Massive to centrilobular necrosis Necrosis

11. Stomach: Gastric ulcer

12. Heart: epicardial hemorrhage

13. Heart: epicardial hemorrhage

14. Heart: Myocardial hemorrhage

15. Skeletal muscle: Necrosis and calcification Necrosis

16. Skeletal muscle: Necrosis and calcification White areas are necrotic and gritty (calcification)

17. Skeletal muscle: Necrosis and calcification Muscle fibers are disrupted and hypercellular

18. Skeletal muscle: Necrosis and calcification Calcification