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INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS

INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS. DR. JOSEPH PURITA MD, FACS, FAAOS, FAAPM www.stemcellorthopedic.com and STEM CELL CENTERS OF AMERICA.

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INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS

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  1. INSTITUTE OF REGENERATIVE AND MOLECULAR ORTHOPEDICS DR. JOSEPH PURITA MD, FACS, FAAOS, FAAPM www.stemcellorthopedic.com and STEM CELL CENTERS OF AMERICA

  2. THE USE OF SUPPLEMENTS AND CYTOKINES IN PLATELET RICH PLASMA INJECTIONS AND STEM CELL TREATMENTS

  3. WHAT CAN WE DO TO PREPARE THE BODY FOR STEM CELL AND PLATELET RICH PLASMA (PRP) INJECTIONS ?

  4. Conditions that Promote Inflammatory Cytokines • Declining sex steroids -Testosterone, estrogen, androstenedione, also growth hormone (Anabolic) • Obesity • Smoking • Subclinical bacterial infections • Increasing BMI • Arteriosclerosis • Diet • Glucose • Excess calories

  5. Although adult stem cells have been considered an attractive source for cell therapy, their effectiveness and efficiency is hindered by a frequently low survival rate due to their exposure to a high cellular stress environment upon transplantation. This key limitation is observed when utilizing adult stem cells for regenerative purposes, as typical cell engraftment yields are extremely low (3%)

  6. Inflammatory Markers and Mediators 1. TNF-α 2. Nuclear Factor Kappa 3. Interleukins 4. C- reactive protein 5. Eicosanoids 6. Cyclooxygenase 7. Lipoxygenase

  7. Multiple factors contribute to this low rate of cell survival, including the harsh environment of the recipient site (EXTRA CELLILAR MATRIX), harboring pro-apoptotic factors including hypoxia, malnutrition, pro-inflammatory cytokines and reactive oxygen and nitrogen species.

  8. TNF-α Acute Chronic 1. Cytokine released in response to cellular stress, damage and infection 2. Anti tumor compound produced by macrophages 3. Activates bactericidal effects of neutrophils 1. Can lead to chronic inflammation Activates nuclear factor kappa-B which initiates inflammatory gene expression and pro-inflammatory enzymes including COX-2 and lipoxygenases 2. Increases thrombosis 3. Decreases cardiac contractility May be implicated in tumor initiation and promotion (Kundu et al. 2008

  9. C-reactive Protein Acute Chronic • Acute phase protein synthesized by liver • during initial • inflammatory response  “coats” damaged cells for • recognition by immune cells • Strong association with elevated risk of • cardiovascular disease and • stroke (Emerging Risk Factors Collaboration • et al. 2010)

  10. Cyclooxgenases & Lipoxygenases acute chronic • Catalyze first steps in synthesizing eicosanoids • converting omega-3 and omega-6 into necessary thromboxanes and • prostaglandins • Lipoxygenases convert fatty acids into pro-inflammatory • leukotrienes necessary for local inflammatory mediation • Recruit WBC’s to site of inflammation • Chronic production of pro-inflammatory • prostaglandins, leukotrienes, • thromboxanes, cytokines amplifying inflammatory response

  11. IF WE ELIMINATE INFLAMMATION WE MAY TURN OFF CERTAIN DISEASES

  12. HOW DO WE ELIMINATE INFLAMMATION? Certain forms of inflammation are necessary for the body to heal itself. Nsaids (Advil, Aleve etc.) and cortisone can relieve inflammation but have many serious side effects and actually stop the body from trying to heal itself. In the long term these are usually not effective in eliminating the disease process.

  13. WHAT SEEMS TO BE THE ROOT OF INFLAMMATION? INFLAMMATION SEEMS TO BE RELATED TO THE FORMATION OF FREE RADICALS. AS WE USE OXYGEN WE FORM FREE RADICALS.

  14. UNDERSTANDING FREE RADICALS Here we see the chemistry. The free electron causes the damage.

  15. WHAT PART OF THE CELLS RECEIVE THE MOST DAMAGE? THE CELL POWERHOUSES, NAMELY THE MITROCHONDRIA

  16. WHERE DO FREE RADICALS COME FROM? • THEENVIRONMENT(air pollution, drugs, certain foods) • INTERNAL PRODUCTION(the bodies own production). • STRESS FACTORS(aging, trauma, disease and infection). • CHAIN REACTIONresulting in DNA damage

  17. FREE RADICALS ARE CELLULAR KILLERS!!! • THEY DAMAGE DNA. • THEY ALTER BIOCHEMICAL COMPOUNDS AND REACTIONS. • THEY DESTROY CELL MEMBRANES. • THEY DESTROY CELLS OUTRIGHT. THEY WILL DAMAGE CELLS CAUSING THEM TO LOSE SOME GENETIC MAKE-UP. THESE DAMAGED CELLS GO ON AND CAUSE DISEASES.

  18. WHAT CAN PROTECT US FROM FREE RADICALS? We must look at the ORAC level of foods and medications. ORAC= OXYGEN RADICAL ABSORBANCE CAPACITY The higher the ORAC number the better the food or medication is in fighting free radicals. REMEMBER ELIMINATING FREE RADICALS SLOWS DOWN DISEASES, AGING ETC.

  19. ORAC VALUES OF CERTAIN FOODS

  20. FREE RADICAL FIGHTERS Many of the antioxidant fighters are called phytonutrients. These are biologically active compounds that are concentrated in the skins of fruits and vegetables. They are responsible for the flavor, color, and smell of fruits and vegetables. REMEMBER TRY TO EAT FIVE COLORS A DAY!!!

  21. BEST METHODS FOR FIGHTING FREE RADICALS 1. DIET 2. EXERCISE 3. SUPPLEMENTS

  22. DIET Use a Mediterranean type of diet. Low in bad fats, low in bad carbohydrates, low in red meats. This type of diet does wonders in reducing inflammation in the body. The Scripps Institute calls this the anti-inflammatory diet!! REMEMBER FIVE COLORS A DAY!

  23. EXERCISE • Have physical exam by physician. 2 If you are able , embark on a program that in short bursts can elevate heart rate to about 85% of your maximum cardiac rate. This will naturally increase the body’s secretion of HUMAN GROWTH HORMONE (HGH) For every decade of age increase resistive exercises.

  24. SUPPLEMENTS • Are supplements really necessary? • Do they have a place in stem cell therapy? • Can they slow down aging? • Can they help reverse some of the aging processes? • Which are the most important for our purposes? (stem cell production)

  25. THE BEST SUPPLEMENTS FOR OUR PURPOSES? • Omega-3 fatty acids (fish oil) • Resveratrol • Various phytonutrients • Vitamin D-3 and Vitamin C • Carnosine • Stem X Cell supplement • Curcumin UltraCur • Living greens from both the land and the ocean FUCODIN • Nitric Oxide producers such as Neo-40 • Collagen stimulating compounds CH-ALPHA

  26. OMEGA 3 FATTY ACIDS = FISH OIL • Only be concerned with the content of the EPAand DHA products of the fish oil. • The EPA and DHA need to equal 3000mg. You may need to take 6000mg of fish oil to obtain 3000mg of omega 3s. • Put fish oil in the freezer and take them frozen. Use care if taking with blood thinner

  27. It should be noted that the anti inflammatory properties of fish oil are limited to reducing inflammation. Fish oil provides little effect in preventing inflammation. Research is also being conducted to enhance the anti-inflammatory action of fish oil by addition of other dietary supplements and drugs.

  28. EFFECTS OF OMEGA 3 FISH OIL ON CELL MEMBRANE The cell membrane is the eyes and ears of the cell. The cell membrane is basically the brain of the cell. Omega 3s make the cell membrane more receptive to the growth factors.

  29. OMEGA 3 FISH OIL Interestingly, researchers found an inverse relationship between levels of Omega-3 in the blood and telomere shortening: the more Omega-3 found in a patient’s blood, the less telomere shortening the patient had undergone over those years. The telomeres are the DNA ends.

  30. OMEGA 3 FATTY ACIDS Association of marine omega-3 fatty acid levels with telomere aging in patients with coronary heart disease was published in the January 20, 2010 issue of the Journal of the American Medical Association. This study showed that over approximately a 5 year period telomere shortening was significantly reduced in the Omega 3 group.

  31. OMEGA 3 FISH OIL It is possible that Omega-3 acids could increase the activity of telomerase in human cells and/or reduce the impact of oxidative stress on telomeres.

  32. RESVERATROL Derived from red wine, resveratrol has demonstrated significant health benefits ranging from cardiovascular protection to anti-cancer effects. It is believed that resveratrol works by mimicking the effects of calorie restriction, the best anti-aging strategy to date, through mechanisms such as reducing oxidative stress, boosting energy production, and regulating gene expression.

  33. RESVERATROL • Activates the SIRTUIN gene. The Sirtuin gene is normally inactive after age 40. This is called gene silencing. When the gene is active it triggers a survival mechanism that appears to extend life. • Research performed at Harvard University. • Seems to mimic many of the effects seen in calorie restrictions and exercise. • There seems to be increase in stem cell production.

  34. RESVERATROL DOSAGE • No clear cut answer. • One class of RED wine has between 0.5-1 mg of resveratrol. • Probably need to take at least 500mg of trans Resveratrol per day. • If taking blood thinner check the blood thinning.

  35. GENE SILENCING As we age certain genes become inactive or SILENCED. Many of these genes protect us against diseases (cancers) and the ravages of aging. If these silenced genes can be turned back on they will protect us from these problems!!!!!! Much in the same way a 20 age old is protected from these diseases.

  36. VITAMIN D At least 2,000 genes, or nearly 10% of your genes, have been identified that are directly influenced by vitamin D, which in turn impact a wide variety of health issues, from preventing the common cold and flu to inhibiting at least 16 different types of cancer. There’s even evidence linking vitamin D to the process of brain detoxification of heavy metals such as mercury.

  37. VITAMIN D One of the most important genes Vitamin D up-regulates is for cathelicidin, a naturally occurring broad-spectrum antibiotic. Vitamin D's final metabolic product is a potent, pleiotropic, repair and maintenance, seco-steroid hormone .

  38. A growing body of evidence indicates that rickets in children and osteomalacia in adults (both a softening of bones due to defective bone mineralization) are just the tip of a vitamin D-deficiency iceberg. Tuberculosis and various autoimmune diseases, such as multiple sclerosis, lupus, and type I diabetes have a causal association with low vitamin D blood levels. Vitamin D deficiency plays a causal role in Hypertension, coronary artery disease, congestive heart failure, peripheral vascular disease, and stroke. It is also a risk factor for metabolic syndrome and type II diabetes, chronic fatigue, seasonal affective disorder, depression, cataracts, infertility, and osteoporosis. At the bottom of the vitamin D iceberg lies cancer. There is good evidence that vitamin D deficiency is a causal factor in some 15 different common cancers. (NEJM 2007;357:266-81.)

  39. WHAT TYPE OF VITAMIN D TO TAKE? PATIENTS SHOULD BE ADVISED TO TAKE VITAMIN D3. OTHER FORMS OF VITAMIN D DO NOT HAVE THE BENEFITS AND CAN BE TOXIC TO THE LIVER IN HIGH DOSES. THESE FORMS OF VITAMIN D INCLUDE COD LIVER OIL. IT IS BELIEVED THAT VITAMIN D3 IS LIPID AND WATER SOLUBLE.

  40. PATIENTS ARE TO TAKE 2000-5000 I.U. VITAMIN D3 PER DAY

  41. VITAMIN C • Very important in the production of collagen and therefore cartilage • Also acts as a good anti-oxidant

  42. STEM X CELL STEM CELLS AND DEVELOPMENT 15:118–123 (2006) Original Research Report “Nutriceutical Synergistically Promote Proliferation of Human Stem Cells” PAULA C. BICKFORD, JUN TAN, R. DOUGLAS SHYTLE, CYNDY D. SANBERG, NAGWA EL-BADRI, and PAUL R. SANBE

  43. STEM X CELL CONTENTS • VITAMIN D-3 2000 UNITS • CARNOSINE • BLUEBERRY EXTRACT • GREEN TEA EXTRACT • A VARIETY OF ENZYMATIC EXTRACTS

  44. A dose-related effect of blueberry, green tea, catechin,Carnosine, and vitamin D3 was observed on proliferation with human bone marrow as comparedwith human granulocyte-macrophage colony-stimulating factor (hGM-CSF)

  45. Melatonin-N-acetyl-5-methoxytryptamine • Secreted by pineal gland as well as extra pineal production • • Produced in darkness, suppressed by light • • Concentrated in nucleus and mitochondria • • Levels decline with aging - 10-15% per decade • • Manages circadian rhythm of inner clock • • Controls sleep wake cycle

  46. MELATONIN =The ultimate anti-oxidant Reiter RJ et al. Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol J Pharmacology. 2004 Mar-Apr;56(2):159-70

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