Sunday, December 17, 2017

Effectiveness of Platelet-Rich Plasma (PRP) Treatment

Despite the numerous benefits ascribed to Platelet-rich plasma (PRP) and the promising results reported for its therapeutic potential, the clinical outcomes are heterogeneous and sometimes contradictory. These controversial findings are due to both the different clinical protocols applied and the a great number of PRP products with different qualities.

These variables—which may affect the Effectiveness of PRP treatments—are mainly related to:
  • PRP Preparation Methods
    • Collecting Blood
    • Harvesting PRP
  • Type of Activators
  • Types of Body Area to Be Treated
  • Ways and Times of Administration
In this article, we will try to shed some light on these topics.

PRP Preparation Methods

PRP is prepared by withdrawing peripheral blood and concentrate platelets to 3–10 times physiological levels. The platelets then undergo degranulation to release growth factors (GFs) with healing properties. The plasma contains cytokines, thrombin, and other GFs, with inherent biological and adhesive properties.

Currently, there is still lack of standardization in PRP preparation procedures. This has led to the availability of a huge number of products differing in terms of cell types, quantity and therefore GF and cytokine content and release times.

Blood used in PRP preparation can be obtained from different sources:
Based on different blood sources, there are different preparation considerations.

Collecting Blood

Autologous Blood

If blood is withdrawn from patient's own, its advantages include:
  • No concern for disease transmission
  • Minimal or no hypersensitivity reactions or allergic reaction
    • Its biocompatible and biodegradable properties prevent the autologous PRP from inducing foreign body reactions, tissue necrosis, or extensive fibrosis.[24].

Pooled Blood

Because the possibility of disease transmission from donors, pooled blood normally will be treated with virus inactivation first.

 For instance, pooled blood could be virally inactivated by solvent/detergent (S/D) treatment, which  is usually administered after the centrifugation in PRP preparation. Finland started to use SD plasma in 2007 and since 2013 all units administered are pathogen-reduced by SD treatment.[10]

Harvesting PRP

The next step in PRP preparation is to obtain a highly concentrated sample of platelets using centrifuge.

Platelets actively participate in healing processes by delivering a broad spectrum of GFs and other active molecules to the injured site by exocytosis following adhesion or stimulation by thrombin and other strong stimuli-like calcium.

There are different techniques for harvesting PRP, which can be divided broadly into two protocols:
  • One spin technique
  • Two spin technique
    • See above diagram
Concentrated sample of platelets can further processed to produce derivative products such as:
  • Platelet rich fibrin matrix (PRFM)
    • PRP is converted to PRFM through a controlled process, creating a scaffold that serves to protect and preserve platelets. 
    • Fibrin acts as a provisional scaffold for stem or primary cell migration and differentiation and functions as a biological glue in vivo.
The concentration of platelets obtained by each method differs. In addition, platelet content can be affected by:
  • Donor's gender
    • Higher with female than male plasma
  • Personal physical aspects (excludes age)
In contrast, the GF content is not influenced by age or gender even the content might differ in the same individual with use of different systems or different manufacturers.[3]

GFs secreted by platelets include:

Some of the growth factors (GFs) present in PRP could have negative effects in some types of PRP administration—For example, on the osteoarthritis (OA) joint:[3]
It is therefore unlikely that a mix of GFs some of which have negative effects in the OA joint, as present in PRP, will be of benefit in OA. Future directions of PRP application may concentrate on seeking an appropriate and innocuous agent like anti-VEGF antibody that can modulate and control the effect of PRP.

Finally, special care must be taken on:
  • Blood extraction tools
  • Machines for blood centrifugation 
  • CaCl solutions or similar activation agents
to prevent contamination of the compound.  The process must be kept sterile and precisely suited to separate platelets from red blood cells. Unless platelet sequestration is done carefully and without causing any damage, platelets will no longer be able to secrete growth factors actively.

Type of Activators

Platelet activation increases levels of anti-inflammatory cytokines because of the presence of hepatocyte GF. These GFs have a particular function in bone remodeling and wound healing as well as stimulation of cartilage matrix synthesis and affect catabolic cytokines such as IL-1, IL-4, IGF-1, osteogenetic protein (OP)-1, FGF, TGFs and PDGF12.

An activation step before PRP administration is included in many of the protocols used.  The GFs will release after exogenous or endogenous activation. Different methods of activating PRP probably affect the concentration of GFs.  PRPs are commonly activated exogenously by:
  • Calcium Chloride (CaCl2)
    • 5% calcium chloride treatment for 19 min produces the most effective PRP, which have properties for soft-tissue adhesion.[21]
  • Thrombin
  • Chitosan
    • In [22], the study demonstrated that chitosan gel could be an appropriate carrier for PRP applications by providing sustained release of GFs.
  • Batroxobin
As well as platelet content, concentration of GFs differs between each person.[3]

Types of Body Area to Be Treated

Growth factor and cytokine concentrations were influenced by the cellular composition of PRP. For example, platelets can increase anabolic signaling and, in contrast, leukocytes can increase catabolic signaling molecules.  Depending on the clinical application, preparations of PRP should be considered based on their ability to concentrate platelets and/or GFs with sensitivity to pathologic conditions.[20]

The differences among concentration  and activation methods might allow PRP preparations to be optimized, by identifying the most suitable strategy for each specific clinical application:
  • Treatment of chronic skin and soft tissue ulcerations [27-29]
  • Periodontal and oral surgery [32-36]
  • Maxillofacial surgery[32,32,34.37]
  • Orthopedic and trauma surgery[34,38-40]
  • Cosmetic and plastic surgery[40,41]
  • Spinal surgery [32,37], heart bypass surgery[32], and burns [42].
in order to obtain a customized PRP for the various clinical indications.

Ways and Times of Administration

The ways and times of PRP administration depends on the area of the body being treated and they can vary:
  • Injection (
    • Could be intradermal injection, subcutaneous injectionsintramuscular injections, intraarticular injection, etc
      • In [31], the study compares the efficacy and safety of two administration modes of autologous PRP (intradermal injection (ID) and topical application) after FCL with that of FCL alone in the treatment of atrophic acne scars.
      • In [18], authors conclude that Intra-articular PRP injection could offer better symptomatic relief to patients with early knee degenerative changes.  However, they also warn that "there appears to be an increased risk of local adverse reactions after multiple PRP injections."
    • Injections are normally performed under image guidance to assure precise placement of PRP. 
    • The number of injections varies based on each patient’s individualized condition and the condition to be treated.  For treating musculoskeletal conditions, it typically range anywhere from two to six injections done over time.[26]
  • Topical Administration
    • PRP has a strong stimulant effect on capillary regeneration in wound healing. These effects are mainly noticeable during the early stages of wound healing.[33]

All Factors Considered

All factors that can influence the effectiveness of PRP treatment include:
  • Overall health of the patient
    • At the time of blood withdrawl
      • Some PRP products can have PRP preserved and protected for up to 1-2 years before usage
    • At the time of PRP treatment
  • Acute vs chronic injury
  • PRP preparation methods
    • Can some GFs be filtered out if they have negative effects in some treatments?
    • Can an agent like anti-VEGF antibody be added to modulate and control the effect of PRP?
  • How and when platelets are activated
  • Types of body area to be treated
  • Ways and times of administration
To summarize, the effectiveness of the treatment depends on many actors in the pipeline: patient, PRP product, and health carer.  Therefore, PRP treatment plan should and better be customized towards individual's needs.


  1. M. Tschon, M. Fini, R. Giardino et al., “Lights and shadows concerning platelet products for musculoskeletal regeneration,” Frontiers in Bioscience-Elite, vol. 3, no. 1, pp. 96–107, 2011
  2. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules
  3. Y. Zhu, M. Yuan, H. Y. Meng et al., “Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review,” Osteoarthritis and Cartilage, vol. 21, no. 11, pp. 1627–1637, 2013.
  4. T. E. Foster, B. L. Puskas, B. R. Mandelbaum, M. B. Gerhardt, and S. A. Rodeo, “Platelet-rich plasma: from basic science to clinical applications,” The American Journal of Sports Medicine, vol. 37, no. 11, pp. 2259–2272, 2009.
  5. B. Di Matteo, G. Filardo, E. Kon, and M. Marcacci, “Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy—a systematic review,” Musculoskeletal Surgery, vol. 99, no. 1, pp. 1–9, 2015
  6. Regenerative medicine: Current therapies and future directions
  7. Burnouf, T., et al., A virally inactivated platelet-derived growth factor/vascular endothelial growth factor concentrate fractionated from human platelets. Transfusion, 2010. 50(8): p. 1702-11.
  8. Solvent/detergent treatment of human plasma--a very robust method for virus inactivation. Validated virus safety of OCTAPLAS.
  9. Health Technology Assessment of pathogen reduction technologies applied to plasma for clinical use
  10. European Directorate for the Quality of Medicines & HealthCare. Symposium on Implementation of Pathogen Reduction Technologies for Blood Components. Executive Summary; Strasbourg, France. 2010
  11. Virus-inactivated plasma - Plasmasafe: a one-year experience
  12. Burnouf, T., et al., Human blood-derived fibrin releasates: composition and use for the culture of cell lines and human primary cells. Biologicals, 2012. 40(1): p. 21-30.
  13. Burnouf, T., et al., Solvent/detergent treatment of platelet concentrates enhances the release of growth factors. Transfusion, 2008. 48(6): p. 1090-8.
  14. Shih, D.T., et al., Expansion of adipose tissue mesenchymal stromal progenitors in serum-free medium supplemented with virally inactivated allogeneic human platelet lysate. Transfusion, 2011. 51(4): p. 770-8.
  15. Su, C.Y., et al., Quantitative assessment of the kinetics of growth factors release from platelet gel. Transfusion, 2008. 48(11): p. 2414-20.
  16. A. S. Wasterlain, H. J. Braun, and J. L. Dragoo, “Contents and formulations of platelet-rich plasma,” Operative Techniques in Orthopaedics, vol. 22, no. 1, pp. 33–42, 2012
  17. J. A. Textor, J. W. Norris, and F. Tablin, “Effects of preparation method, shear force, and exposure to collagen on release of growth factors from equine platelet-rich plasma,” American Journal of Veterinary Research, vol. 72, no. 2, pp. 271–278, 2011
  18. Campbell, K.A., Saltzman, B.M., Mascarenhas, R. et al. Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy. 2015; 31: 2213–2221
  19. What’s New in Knee Osteoarthritis Treatments? (WebDB)
  20. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma.
  21. Luengo Gimeno, F., Gatto, S., Ferro, J., Croxatto, J.O., and Gallo, J.E. Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits. Thromb J. 2006; 4: 18
  22. Kutlu, B., Tigli Aydin, R.S., Akman, A.C., Gumusderelioglu, M., and Nohutcu, R.M. Platelet-rich plasma-loaded chitosan scaffolds: preparation and growth factor release kinetics. J Biomed Mater Res B Appl Biomater. 2012; 101B.
  23. How We Grow: Anabolic Signaling Mechanisms
    • Our bodies use anabolic signaling mechanisms to communicate to our muscles that they need to grow.
  24.  Dijkstra-Tiekstra MJ, Van der Schoot CE, Pietersz RN, Reesink HW. White blood cell fragments in platelet concentrates prepared by the platelet-rich plasma or buffy-coat methods. Vox Sang. 2005;88:275–7.
  25. Study of Platelet-Rich Plasma Injections in the Treatment of Androgenetic Alopecia Through an One-Year Period.
  26. PRP (Virginia Spine Institute) 
  27. Pietrzak WS, Eppley BL. Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005;16(6):1043–1054.
  28. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plast Reconstr Surg. 2006;118(6):147e–159e.
  29. Salemi S, Rinaldi C, Manna F, Guarneri GF, Parodi PC. Reconstruction of lower leg skin ulcer with autologous adipose tissue and platelet-rich plasma. J Plast Reconstr Aesthet Surg. 2008;61(12):1565–1567.
  30. Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
  31. Autologous Platelet Rich Plasma: Topical Versus Intradermal After Fractional Ablative Carbon Dioxide Laser Treatment of Atrophic Acne Scars
  32. Pietrzak WS, Eppley BL. Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005;16(6):1043–1054.
  33. Lindeboom JA, Mathura KR, Aartman IH, Kroon FH, Milstein DM, Ince C. Influence of the application of platelet-enriched plasma in oral mucosal wound healing. Clin Oral Implants Res. 2007;18(1):133–139. [PubMed]
  34. El-Sharkawy H, Kantarci A, Deady J. et al. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol. 2007;78(4):661–669. [PubMed]
  35. Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev. 2008;14(3):249–258. [PubMed]
  36. Shashikiran ND, Reddy VV, Yavagal CM, Zakirulla M. Applications of platelet-rich plasma (PRP) in contemporary pediatric dentistry. J Clin Pediatr Dent. 2006;30(4):283–286. [PubMed]
  37. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plast Reconstr Surg. 2006;118(6):147e–159e. [PubMed]
  38. Wrotniak M, Bielecki T, Gazdzik TS. Current opinion about using the platelet-rich gel in orthopaedics and trauma surgery. Ortop Traumatol Rehabil. 2007;9(3):227–238. [PubMed]
  39. Mishra A, Woodall J Jr, Vieira A. Treatment of tendon and muscle using platelet-rich plasma. Clin Sports Med. 2009;28(1):113–125. [PubMed]
  40. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res. 2005;84(5):434–439. [PubMed]
  41. Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg. 2002;18(1):27–33. [PubMed]
  42. Henderson JL, Cupp CL, Ross EV. et al. The effects of autologous platelet gel on wound healing. Ear Nose Throat J. 2003;82(8):598–602. [PubMed]

Friday, December 1, 2017

All Things Considered—Kidney Disease

A national survey found that only 41% of Americans tested had normal kidney function, a drop from 52% about a decade earlier.[1]

If your kidneys do not function property, metabolic waste products can accumulate in the blood and eventually lead to such symptoms as weakness, shortness of breath, confusion, and abnormal heart rhythms.  If your kidneys fail completely, you will either need a new one or have to go on dialysis. However, the average life expectancy of a person on dialysis is less than 3 years.[3]

So, it's better to keep your kidneys healthy in the first place.

Kidney Problems

Healthy kidneys work hard to retain protein and other vital nutrients, preferably filtering toxic or useless wastes out of the blood stream via your urine.  Patients with kidney problems can range from experiencing no symptoms to leaking protein into urine or to end-stage renal disease.
  • Poor kidney function is not just a kidney disease
    • Kidney malfunction can be so damaging to the rest of the body that most people don't live long enough to reach end-stage kidney failure.
    • Poor kidney function is associated with diabetes, hypertension, and heart disease.
      • For instance,  your kidneys are so critical to proper heart function that patients under age 45 with kidney failure can be 100 times more likely to die of heart disease than those with working kidneys.[3]
  • Each year, 64,000 Americans are diagnosed with kidney cancer, and about 14,000 die from it.[29]
  • Most kidney disease is characterized by a gradual loss of function over time.
    • Common signs of kidney problems include frequent urination, problems urinating, and constant thirst
  • Kidney Stones
    • Read the companion article "Types of Kidney Stones "
    • Approximately one in eleven Americans are affected toay, compared with one in twenty less than two decades ago.[20]

Renal Function Test

Creatinine is removed from the blood chiefly by the kidneys. Little or no tubular reabsorption of creatinine occurs. If the filtration in the kidney is deficient, creatinine blood levels rise. Therefore, creatinine levels in blood and urine may be used for kidney function tests.
  • Creatinine Clearance
    • A decreased creatinine clearance indicates poor renal function. Normal creatinine level is between 80 - 120 μmol/L. 
  • Serum Creatinine
    • Serum creatinine may be more useful clinically when dealing with patients with early kidney disease.
  • Glomerular Filtration Rate (GFR)
    • Blood creatinine levels may also be used alone to calculate the estimated GFR (eGFR).
    • A normal eGFR for adults is greater than 90 mL/min/1.73m2, according to the National Kidney Foundation. (Because the calculation works best for estimating reduced kidney function, actual numbers are only reported once values are less than 60 mL/min/1.73m2).

Risk Factors of Kidney Diseases

  • Animal Products[4]
    • Researchers at Harvard University found three specific dietary components associated with declining kidney function:  animal protein, animal fat, and cholesterol.
    • And they found no association between kidney function decline and the intake of protein or fat from plant sources.
  • Kidney Stones
    • Read the companion article "Risk Factors of Kidney Stones"
    • When urine is more alkaline, stones are less likely to form and vice versa.
    • A high intake of zinc was associated with a higher risk.[21]
  • Lipid Nephrotoxicity
    • Fat and cholesterol in the blood stream could be toxic to the kidneys.[5,6]
  • "Meat-Sweet" Diet[7]
    • Excess table sugar and high-fructose corn syrup consumption is associated with increased blood pressure and uric acid levels, both of which can damage the kidney.
    • The saturated fat, trans fat, and cholesterol found in animal products and junk food are associated with impaired kidney function, and meat protein increases the acid load in the kidneys, boosting ammonia production and potentially damaging our sensitive kidney cells.[8,14]
  • Excess Phosphorus Intake
    • Having too much phosphorus in the blood may increase the risk of kidney failure, heart failure, heart attacks, and premature death.[24]
    • Phosphate (in animal foods) vs Phytate (in plant foods)[26]
      • Phosphorus in meat is present within the cells as organic phosphates, which is easily hydrolyzed and absorbed. 
      • Because mammals lack the degrading enzyme phytase, bioavailability of phosphorus from plant-derived foods is relatively low, despite their high phosphorus content.
    • Inorganic phosphate vs organic phosphate[26,27,28]
      • Inorganic phosphate from additives is readily absorbable and the worst offenders.
  • Inheritance
    • Approximately 4% of kidney cancer are hereditary.[30]
  • Tobacco Use (hint: nitrosamines)[30]
    • Similar to tobacco carcinogens, you can find both nitrosamines and nitrosamides in processed meats
    • Nitrites themselves are not carcinogenic.  However, if they turn into nitrosamines and nitrosamides, then they are.
      • With amines and amides, which are abundant in animal products, nitrites can be transformed to carcinogen.
      • In the case of plant foods, the vitamin C and other antioxidants that are found naturally in them block the formation of these carcinogens in your body.[31]
  • Dietary Acid Load[8,14]
    • Dietary acid load is determined by the balance of acid-inducing foods (such as meats, eggs, and cheese) and base-inducing foods (such as fruites and vegetables).
    • A higher dietary acid load was associated with significantly higher risk of protein leakage into the urine, an indicator of kidney damage.[14]

How Not to Die from Kidney Disease[12]

  • Protein restricting diet
    • A restriction of protein intake is often recommended to chronic kidney disease patients to help prevent further functional decline.[9]
  • Eating plant-based diets
    • People eating a plant-based diets appear to have better kidney function.
      • Originally thought to be due to their lower overall protein intake[10]
      • However, we now know that it's more likely due to the fact that the kidneys appear to handle plant protein very differently from animal protein.[11]
    • Half a dozen clinical trials have shown that plant protein replacement can reduce hyperfiltration and/or protein leakage.[12]
      • Why does animal protein cause the overload reaction while plant protein doesn't? Because of the inflammation animal products can cause.[13]
    • Uric acid stones—the 2nd most common type of kidney stones—can apparently be dissolved away completely with a combination of eating more fruits and vegetables, restricting animal protein and salt intake, and drinking at least ten glasses of fluid a day.[23]
    • While nitrite from animal sources was associated with an increased risk o kidney cancer, some of the highest nitrate-containing vegetables, such as arugula, kale, and collards, are associated with significantly reduced risk for kidney cancer.[32]
  • Avoid meat-rich diet
    • The chronic, low-grade, metabolic acidosis attributed to a meat-rich diet helps explain that:
      • Why people eating plant-based diets appear to have superior kidney function.[15]
      • Why various plant-based diets have been so successful in treating chronic kidney failure.[16-19]
    • Oxford University researchers found that subjects who didn't eat meat all all had a significantly lower risk of being hospitalized for kidney stones, and for those who did eat meat, the more they ate, the higher their associated risk.[21]
  • Phosphate (in animal foods) vs Phytate (in plant foods)
    • Most Americans consume about twice as much phosphorus as they need.[25]
    • Phosphate is absorbed into the bloodstream more readily than phytate.[26]
    • Avoid Phosphate additives in cola drinks and meat (for enhancing color)
      • Phosphate additives have been described as "a real and insidious danger" for kidney patients, since they have diminished capacity to excrete it.[27]
      • A supermarket survey found more than 90% of chicken products contained phosphate additives.[28]


  1. Coresh J, Selvin E, Stevens LA, et al.  Prevalence of chronic kidney disease in the United States.  JAMA, 2007;298(17):2038-47.
  2. Stokes JB.  Consequences of frequent hemodialysis: comparison to conventional hemodialysis and transplantation.  Trans Am Clin Climatol Assoc.  2011;122:124-36
  3. Kumar S, Bogle R. Banerjee D. Why do young people with chronic kidney disease die early?  World J Nephrol. 2014;3(4):143-155.
  4. Lin J, Hu FB, Curhan GC.  Associations of diet with albuminuria and kidney function decline.  Clin J Am Soc Nephrol. 2010;5(5):836-43.
  5. Moorheaqd JF, Chan MK, El-Nahas M, Varghese Z. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease.  Lancet.  1982;2(8311):1309-11.
  6. Hartroft WS.  Fat emboli in glomerular capillaries of choline-deficient rats and of patients with diabetic glomerulosclerosis, Am J Pathol.  1955;31(3):381-97.
  7. Odermatt A.  The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease.  Am J Physiol Renal Physiol, 2011; 301(5):F919-31.
  8. van den Berg E, Hospers FA, Navis G, et al.  Dietary acid load and rapid progression to end-stage renal disease of diabetic nephropathy in Westernized South Asian people.  J Nephrol. 2011; 24(1):11-7.
  9. Piccoli GB, Vigotti FN, Leone F, et al.  Low-protein diets in CKD: how can we achieve them? A narrative, pragmatic review.  Clin Kidney J. 3015;8(1):61-70.
  10. Wiseman MJ, Hunt R, Goodwin A, Gross JL, Keen H, Viberti GC.  Dietary composition and renal function in healthy subjects.  Nephron.  1987;46(1):37-42.
  11. Nakamura H, Takasawa M, Kashara S, et al.  Effects of acute protein loads of different sources on renal function of patients with diabetic nephropathy.  Tohoku J Exp Med. 1989;159(2):153-62.
  12. How Not to Die (Dr. Michael Greger), Chap 10;Ref 24-30.
  13. Fioretto P, Trevisan R, Valerio A, et al.  Impaired renal response to a meat meal in insulin-dependent diabetes:  role of glucagon and prostaglandins.  Am J Physiol, 1990;258(3 Pt 2):F675-83.
  14. Banerjee T, Crews DC, Wesson DE, et al.  Dietary acid load and chronic kidney disease among adults in the United States.  BMC Nephrol. 2014 Aug 24;15:137.
  15. Wiseman MJ, Hunt R, Goodwin A, Gross JL, Ken H, Viberti GC. Dietary composition and renal function in healthy subjects.  Nephron. 1987;46(1):37-42.
  16. Kempner W. Treatment of heart and kidney disease and of hypertensive and arteiosclerotic vascular disease with the rice diet.  Ann Intern Med. 1949;31(5):821-56.
  17. Barsotti G, Morelli E, Cupisti A, Meola M, Dani I., Giovannetti S.  A low-nitrogen low-phosphorus vegan diet for patients with chronic renal failure.  Nephron.  1996;74(2):390-4.
  18. Goraya N, Simoni J, Jo C, Wesson DE. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy.  Kidney Int. 2012;81(1):86-93.
  19. Uribarri J, Oh MS.  The key to halting progression of CKD might be in the produce market, not in the pharmacy.  Kidney Int. 2012;81(1):7
  20. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project, Prevalence of kidney stones in the United States.  Eur Urol. 2012;62(1):160-5.
  21. Turney BW, Appleby PN, Reynard JM, Nobel JG, Key TJ, Allen NE.  Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).  Eur J Epidemiol. 2014;29(5):363-9.
  22. Siener R, Hesse A.  The effect of a vegetarian and different omnivorous diets on urinary risk factors for uric acid stone formation.  Eur J Nutr. 2003;42(6):332-7.
    • Removing all meat from a standard Western diet appears to reduce the risk of uric acid crystallization—the 2nd most common type of kidney stones—by more than 90% within as few as five days.
  23. Kim JW, et al. Increased fluid intake and adequate dietary modification may be enough for the successful treatment of uric acid stone.  Urolithiasis. 2013;41(2):179-82.
  24. Ritz E, Hahn K, Ketteler M, Kuhlmann MK, Mann J. Phosphate additives in food—a health risk.  Dtsch Arztebl Int. 2012;109(4):49-55.
  25. Calvo MS, Uribarri J. Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population.  Am J Clin Nutr. 2013;98(1):6-15.
  26. Fukagawa M, Komaba H, Miyamoto K. Source matters: from phosphorus load to bio-availability. Clin J Am Soc Nephrol. 2011;6(2):239-40
  27. Benini O, D'Alessandro C, Gianfaldoni D, Cupisti A.  Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients.  J Ren Nutr. 2011;21(4):303-8.
  28. Sullivan CM, Leon JB, Sehgal AR.  Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients.  J Ren Nutr. 2007;17(5):350-4.
  29. American Cancer Society.  Cancer Facts & Figures 2014.  Atlanta: American Cancer Society; 2014.
  30. Kirkali A, Cal C. Renal Cell Carcinoma: Overview. In Nargund VH, Raghavan D, Sandler HM, eds.  Urological Oncology. London, UK: Springer; 2008:263-80.
  31. Bartsch H, Ohshima H, Pignatelli B. Inhibitors of endogenous nitrosation.  Mechanisms and implications in human cancer prevention.  Mutat Res. 1988;202(2):307-24.
    • Such inhibitors of nitrosation include vitamins C and E, phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts
  32. Liu B, Mar Q, Wang X, et al.  Cruciferous vegetables consumption and risk of renal cell carcinoma: a meta-analysis.  Nutr Cancer.  2013;65(5):668-76
    • Our findings supported that cruciferous vegetables consumption was related to the decreased risk of renal cell carcinoma.
  33. How to Prevent and Treat Kidney Problems With Food (Dr. Mercola) 
  34. 7 Secrets to Keeping Your Kidneys Healthy
  35. How Not to Die from Kidney Disease

Monday, November 27, 2017

All Things Considered—Prostate Cancer

Nearly 200,000 cases of prostate cancer are diagnosed each year, and nearly 28,000 men die.[19] In a prostate cancer patient's testimony, he describes the disease as:[20,32]
"This is serious, life-changing stuff: There’s blood in your urine, a catheter snaked up your penis, scars stitch your gut, and you might be impotent and incontinent for a few months, a couple of years, or the rest of your life."
Scary! Isn't it?

Prostate Problems

The prostate is a walnut-sized gland located between the bladder and base of the penis, just in front of the rectum. It surrounds the urethra, the outlet from the bladder, and secretes the fluid portion of semen. Just as glandular tissue in the breast can become cancerous, so can glandular tissue in the prostate.

If the cancer is caught while still localized with the prostate, the chances of it killing you within the next five years are practically nil. However, if the cancer spreads far enough, your chances of surviving five years may be as low as one in three.[18,29]

Prostate Cancer Screening

Prostate Cancer Screening measures the level of PSA in the blood.  As a rule, the higher the PSA level in the blood, the more likely a prostate problem is present. But many factors, such as age and race, can affect PSA levels.

Also, noted that PSA test could have two potential issues:
  1. Prostate cancers—detected or undetected—may never have led to harm[49]
    • Autopsy studies show that about half of men over the age of 80 have prostate cancer.[18]
    • Most men die with prostate cancer without ever knowing they had it.
  2. PSA screening can result in a high percentage of false positives
The latest recommendation says that overall, PSA-based screening for men aged 55 to 69 offers a small potential benefit of reducing the chance of dying of prostate cancer.  For men 70 and older, the advisory panel continues to recommend against PSA-based testing, arguing that for this age group, prostate cancer evolves slowly and the 10-year survival rate is relatively high.

Risk Factors of Prostate cancer

  • Environmental quality
    • The risk of prostate cancer in men and breast cancer in women seemed most susceptible to bad environmental quality (i.e., rural vs urban living areas), the research team observed.[12]
  • Higher calcium and/or dairy intakes
    • There is some evidence to suggest that higher calcium (ranging from 600 mg to >2000 mg of calcium) and/or dairy intakes (>2.5 servings) may be associated with the development of prostate cancer.[43-46]
      • However, these studies are observational in nature rather than clinical trials and cannot establish a definite causal relationship between calcium and prostate cancer.
    • At the present time, it is recommended that men ages 19 and over consume a "modest" intake of calcium ranging from 1000-1200 mg per day and maintain an intake below the upper tolerable limit (2500 mg).[47]
  • Alcohol consumption
    • A large amount of alcohol makes the detrusor muscle contract less efficiently and may make any prostate problem worse
  • Milk consumption
    • Growth hormones used in livestock raising
      • A lifetime of human exposure to these growth factors in milk may help explain the connections found between dairy consumption and certain cancers.[24]
      • Experimental evidence suggests that dairy could also promote the conversion of precancerous lesions or mutated cells into invasive cancers.[25]
    • Naturally produced sex steroid hormones
      • Today's genetically "improved" dairy cows are milked throughout their pregnancies when their reproductive hormones are particularly high.[21]
      • Which may lead to hormone-related conditions, including acne, diminished male reproductive potential, and premature puberty.[21-24]
    • A combination of case-control studies and cohort studies concluded that cow's milk consumption is a risk factor for prostate cancer.[26-27]
    • A 2015 meta-analysis found that high intakes of dairy products—milk, low-fat milk, and cheese, but not nondairy sources of calcium—appear to increase total prostate cancer risk.[28]
  • IGF-1
    • The more IGF-1 you have in your bloodstream, the higher your risk for developing cancers, such as prostate cancer[39]
    • The release of IGF-1 appears to be triggered by the consumption of animal protein.[40-41]

How Not to Die from Prostate Cancer[42]

  • Eat plant-based whole foods (especially cruciferous vegetables)[41]
    • The blood of people eating plant-based diets was shown to fight cancer about eight times better.[30]
    • Dr Ornish et al. were able to demonstrate that a full-time plant-based diet allowed for an apparent reversal in cancer growth.
    • Both the historic rarity of BPH and prostate cancer in Japan and China have been attributed to the countries' traditional plant-based diets.[36]
    • Eating garlic and onions has been associated with significantly lower risk of BPH.[37]
    • A UCLA research team compared three groups of men: a plant-based diet-and-exercise group, an exercise-only group, and a control group of sedentary people eating standard fare.[31]
      • The blood of control group killed off 1-2% of cancer cells
      • The blood of exercise-only group killed 2,000% more cancer cells than that of the control groups'
      • However, the winner is the blood from the plant-based diet-and-exercise group, which wiped out 4,000% more cancer cells than that of the control groups'
    • In general, cooked vegetables may work better than raw ones, and legumes—beans, chickpeas, split peas, and lentils—have also been associated with lower risk.[38]
  • Cranberry
    • Cranberry removes purines, uric acid, and toxins from the bladder, kidneys, testicles, and prostate—which means a healthier prostate and less risk of prostate cancer.
  • Watermelon
    • Watermelon contributes to a healthy prostate and its lycopene may reduce risks of prostate cancer.[1]
  • Green tea
    • Based on a meta-analysis, it suggests that regardless of tea type, tea consumption might be a potential protective factor for the prostate caner, especially in China and India.[50]
      • Tea consumption might play a protective role in low-grade prostate caner.
    • But, you might need to drink 6 cups a day to have an impact[52]
      • In Japan, the high tea-drinking group can be five or more cups a day, which appeared to cut the risk of aggressive prostate cancer about in half. 
  • Lignans (hint: flaxseeds)[10]
    • Higher levels of lignans tend to be found in the prostate fluids of populations of men with relatively low rates of prostate caner[33]
    • Lignans have been shown to slow the growth of prostate cancer cells in a petri dish.[34]
    • The evidence suggests that flaxseed is safe, low-cost source of nutrition and may reduce tumor-proliferation rates.[48]
      • Ground flaxseed seems to be quite helpful not just for preventing prostate cancer, but also for men who already have prostate cancer.
      • As well as the phytoestrogen effect, the lignans in flaxseed adhere to hormone receptors and promote the removal of testosterone.
      • In men having prostate cancer, a low fat diet supplemented with 30 grams of ground flaxseed reduces serum testosterone by 15 %, slows down the growth rate of cancer cells, and increases the death rate of cancer cells.
  • Drink almond milk instead of cow milk
    • In a petri dish environment, Japanese researchers have found that cow milk produced an average increase in cancer growth rate of more than 30%. In contrast, almond milk suppressed the growth of the cancer cells by more than 30%.[25]
  • Avoid eggs (hint: choline)
    • Compared with men who rarely ate eggs, men who ate even less than a single egg a day appeared to have twice the risk of prostate cancer progression.[29]
  • Avoid poultry (hint: HCA)
    • Men with more aggressive cancer who regularly ate chicken and turkey had up to four times the risk of prostate cancer progression.[29]
  • Avoid commercially raised animals fed estrogenic hormones to make them gain weight faster and antibiotics to increase growth rate.
    • Residues of these drugs in meat can impact human health adversely.
    • The hormones may promote the development of prostate cancer in men.
    • Antibiotics in meat certainly contribute to the escalating problem of antibiotic-resistant bacteria, which are becoming prevalent in the world.


  1. "Juiceman's Power of Juicing" by Jay Kordich
  2. Pancreatic Cancer Biomarkers Could Be Detected In Saliva, Mouse Study Shows
  3. New Test for Prostate Cancer (UCSF Medical Center)
  4. Prostate Cancer Symptoms
  5. Prostate Cancer: A Family Affair
  6. Tough Medicine A disturbing report from the front lines of the war on cancer
  7. The Most Common Prostate Cancer Screening Method Is Obsolete
  8. Prevention Tips for Common Cancers (The Asian Fund for Cancer Research, Ltd.)
    • Don’t overeat. Drink green tea
    • Know your family history of cancer
    • Quit smoking
    • Eat more fruits, vegetables, and lean protein
    • Meet with your doctor to develop a plan for physical activity
    • Limit alcohol intake: 2 drinks/day
  9. US panel issues new guidance on prostate cancer screening
  10. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.
  11. Bone health and bone-targeted therapies for prostate cancer
  12. Cancer Risk: Rural areas a bit safer than urban ones
  13. Manipulating Diet May Impact Prostate Cancer Risk, Progression
  14. Treating Advanced Prostate Cancer with Diet
  15. Jackson MD, Walker SP, Simpson-Smith CM, Lindsay CM, Smith G, McFarlane-Anderson N, Bennett FI, Coard KC, Aiken WD, Tulloch T, Paul TJ, Wan RL. Associations of whole-blood fatty acids and dietary intakes with prostate cancer in Jamaica. Cancer Causes Control. 2012 Jan;23(1):23-33.
    • To our knowledge, our study is the first to report an association between avocado consumption and prostate cancer.
    • Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer.
  16. Prostatic Alpha-Linolenic Acid (ALA) Is Positively Associated with Aggressive Prostate Cancer: A Relationship Which May Depend on Genetic Variation in ALA Metabolism
    • We found that while flaxseed supplementation resulted in significantly higher levels of ALA in the diet, this consumption did not translate into higher prostatic levels of ALA. This was an important finding because in additional analyses, prostatic ALA was associated with significantly higher PSA and tumor proliferation rates.
  17. Prostate Cancer Related Videos on
  18. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era. Int J Cancer. 2014; Dec 29.
  19. Cancer for Disease Control and Prevention. Prostate Cancer Statistics.
  20. Person, Patient, Statistic
  21. Maruyama K, Oshima t, Ohyama K. Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows. Pediatr Int. 2010; 52(1): 33-8.
  22. Danby FW. Acne and milk, the diet myth, and beyond. J Am Acad Dermatol. 2005; 52(2):360-2.
  23. Afeiche M, Williams PL, Mendiola J, et al Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men. Hum Reprod. 2013; 28(8):2265-75.
  24. Ludwig DS, Willett WC. Three daily servings of reduced fat milk: an evidence-based recommendation? JAMA Pediatr. 2013; 167(9):788-9.
  25. Tate PL, Bibb R, Larcom LL. Milk stimulates growth of prostate cancer cells in culture. Nutr Cancer. 2011;63(8): 1361-6.
  26. Qin LQ, Xu JY, Wang PY, Kaneko T, Hoshi K, Sato A. Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies. Nutr Cancer. 2004;48(1):22-7.
  27. Qin LQ, Xu JY, Wang PY, Tong J, Hoshi K. Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies. Asia Pac J Clin Nutr. 2007;16(3):467-76.
  28. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117.
  29. Richman EL, Stampfer MJ, Paciorek A, Broering JM, Carroll PR, Chan JM. Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression. Am J Clin Nutr. 2010;91(3):712-21.
    • Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.
  30. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-9.
  31. Barnard RJ, Ngo TH, Leung PS, Aronson WJ, Golding LA. A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro. Prostate. 2003;56(3):201-6.
  32. Frey AU, Sonksen J, Fode M. Neglected side effects after radical prostatectomy a systematic review. J Sex Med. 2014;11(2):374-85.
  33. Morton MS, Chan PS, Cheng C, et al. Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Knong, and the United Kingdom. Prostate. 1997;32(2):122-8.
    • Isoflavanoids (from soy) and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries
  34. Lin X, Switzer BR, Denmark-Wahnefried W. Effect of mammalian lignans on the growth of prostate cancer cell lines. Anticancer Res. 2001;21(6A):3995-9.
  35. Leite KR, Camara-Lopes LH, Cury J, Dall'oglio MF, Sanudo A, Srougi M. Prostate cancer detection at rebiopsy after an intial benign diagnosis: results using sextant extended prostate biopsy. Clinics (Sao Paulo). 2008;63(3):339-42.
  36. Gu F. Epidemiological survey of benign prostatic byperplasia and prostatic cancer in China. Chin Med J. 2000;113(4):299-302.
  37. Galeone C, Pelucchi C, Talamini R, et al. Onion and garlic intake and the odds of benign prostatic hyperplasia. Urology. 2007;70(4):672-6.
  38. Bravi F, Bosetti C, Dal Maso L, et al. Food groups and risk of benigh prostatic hyperplasia. Urology. 2006;67(1):73-9.
  39. Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM. Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis. Int J Cancer. 2009;124(10):2416-29.
  40. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ. The associations of diet with vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev. 2002;11(11):1441-8.
  41. Soliman S, Aronson WJ, Barnard RJ. Analyzing serum-stimulated prostate cancer cell lines after low-fat, high fiber diet and exercise intervention. Evid Based Complement Alternat Med. 2011;2011:529053.
  42. How Not to Die (Dr. Michael Greger)
  43. Janelle KC, Barr SI. Nutrient intakes and eating behavior scores of vegetarian and nonvegetarian women. J Am Diet Assoc 1995;95:180-6
    • Vegans' calcium and vitamin B-12 intakes may need attention
  44. American Dietetic Association, Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. J Am Diet Assoc 2003;103:748-65
  45. Appleby P, Roddam A, Allen N, Key T. Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford. Eur J Clin Nutr. 2007 Dec;61(12):1400-6.
  46. National Institutes of Health. Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement Online 2000:1-45
  47. Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010.
  48. Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery
  49. Zlotta AR, Egawa S, Pushkar D, Govorov A, Kimura T, Kido M, Takahashi H, Kuk C, Kovylina M, Aldaoud N, Fleshner N, Finelli A, Klotz L, Sykes J, Lockwood G, van der Kwast TH. Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. J Natl Cancer Inst. 2013 Jul 17;105(14):1050-8.
  50. Fei X, Shen Y, Li X, Guo H. The association of tea consumption and the risk and progression of prostate cancer: a meta-analysis. Int J Clin Exp Med. 2014 Nov 15;7(11):3881-91.
  51. Hastak K, Gupta S, Ahmad N, Agarwal MK, Agarwal ML, Mukhtar H. Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene. 2003 Jul 31;22(31):4851-9.
  52. Preventing Prostate Cancer with Green Tea (
  53. Breakthroughs in understanding the genetic basis of aggressive prostate cancer
  54. New Prostate Cancer Imaging Tracer Improves Detection

Thursday, November 23, 2017

Use of Platelet-Rich Plasma (PRP) in Regenerative Therapies

Platelet-Rich Plasma (PRP) treatment is one of the most cutting-edge and potentially beneficial types of prolotherapy available today.

What's Prolotherapy

Prolotherapy is short for "proliferation therapy", which can be described as follows:
  • Is an alternative medicine practice
  • Is a nonsurgical treatment which stimulates healing
  • Is also known as regenerative (injection) therapy
  • Works by stimulating the body's own natural healing mechanisms to repair injured musculoskeletal, skin or connective tissues
Types of Prolotherapy include:

In this article, we will focus on the use of PRP in regenerative medicine.

Use of PRP in Regenerative Therapies

Regenerative therapy uses a patient's own tissues to initiate the healing process. With PRP, it uses our platelet-rich plasma to initiate the healing in different treatments:

Growth Factors Released from PRP

Platelets constitute a reservoir of critical growth factors (GFs) and cytokines which may govern and regulate the tissue healing process. The bioactive molecules secreted by platelet α-granules are involved in several cellular activities such as stem cell trafficking, proliferation, and differentiation, with a complex effect on pro/anti-inflammatory and anabolic/catabolic processes.[26]

Moreover, with respect to purified individual GFs, platelets have the theoretical advantage of containing various bioactive molecules with a natural balance of anabolic and catabolic functions, possibly optimizing the tissue environment and favoring the healing process.[26]

Based on this rationale, PRP is an easy, low-cost, and minimally invasive procedure to deliver high concentrations of autologous GFs and cytokines into injured tissues in physiological proportions. This blood-derived product, placed directly into the damaged tissue, either surgically or through injections, has been widely experimented in different fields of medicine.[27-34]

A variety of growth factors can be released from PRP, which could include:[11,12]

Harvesting Platelets

Platelets are very rare as they take up only 0.4% of our blood cells. With the process of PRP harvesting, we can concentrate those platelets in plasma, which we then put platelet-rich plasma in the areas that need regeneration and rejuvenation. Below are the steps of harvesting PRP:
  1. Collecting blood 
  2. Separating the platelets 
    • By using a centrifuge with proprietary tubes 
    • Separate the contents of our blood from the plasma and the platelets. Among the platelets, which areas are higher concentration or lower concentration 
  3. Extracting platelet-rich plasma
There are different techniques that can be used in the process:[11,12]
  • One spin technique
  • Two spin technique
  • Platelet rich fibrin matrix[23]

Activating Platelets

Among the several variables affecting PRP  lysates (or releasates), platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing.[35-36]

The term “activation” refers to 2 key processes that are initiated during PRP preparation:
  1. Degranulation of platelets to release GFs from α-granules
  2. Fibrinogen cleavage to initiate matrix formation
    • A clotting process which allows the formation of a platelet gel, and therefore to confine the secretion of molecules to the chosen site.[26]
In our body, platelets will be activated by the injuries or surgeries. Outside our body, platelets can be exogenously activated by:
  • CaCl2 (or Calcium Gluconate)
  • Thrombin
  • Or a mixture of the above

An activation step before PRP administration is included in many of the protocols used, commonly by adding thrombin and/or calcium chloride (CaCl2), but some physicians prefer to inject PRP in its resting form, relying on the spontaneous platelet activation occurring after exposure to the native collagen present in the connective tissues.[37]


  1. 6 Major PRP Treatment Benefits, Including for Pain, Injury & Arthritis
  2. Platelet-Rich Plasma (PRP) AAOS
  3. Dr PRP USA
  4. Platlett Rich Plasma Therapy
  5. Harvest® SmartPrep® Multicellular Processing System
  6. Platelet-Rich Plasma: Pain Relief for Knee OA (Cleveland Clinic)
  7. Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Systematic Review
  8. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis
  9. PRP & Stem Cell Injections
  10. These Injections Can Help Your Chronic Muscle and Joint Pain
  11. Platelet Rich Plasma (PRP) for Facial Rejuvenation and Hair Growth - Dr. Vishad Nabili | UCLAMDCHAT
  12. To Fill or Not to Fill: Aesthetic Surgery of the Aging Midface | UCLAMDCHAT Webinars
  13. Sanchez-Avila, R.M., et al., Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int Ophthalmol, 2017.
  14. Anitua, E., et al., PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model. Exp Eye Res, 2016. 151: p. 115-21.
  15. Merayo-Lloves, J., et al., Autologous Plasma Rich in Growth Factors Eyedrops in Refractory Cases of Ocular Surface Disorders. Ophthalmic Res, 2015. 55(2): p. 53-61.
  16. Alio, J.L., A.E. Rodriguez, and D. WrobelDudzinska, Eye platelet-rich plasma in the treatment of ocular surface disorders. Curr Opin Ophthalmol, 2015. 26(4): p. 325-32.
  17. Burnouf, P.A., et al., A novel virally inactivated human platelet lysate preparation rich in TGF-beta, EGF and IGF, and depleted of PDGF and VEGF. Biotechnol Appl Biochem, 2010. 56(4): p. 151-60.
  18. Burnouf, T., et al., A virally inactivated platelet-derived growth factor/vascular endothelial growth factor concentrate fractionated from human platelets. Transfusion, 2010. 50(8): p. 1702-11.
  19. Burnouf, T., et al., Human blood-derived fibrin releasates: composition and use for the culture of cell lines and human primary cells. Biologicals, 2012. 40(1): p. 21-30.
  20. Burnouf, T., et al., Solvent/detergent treatment of platelet concentrates enhances the release of growth factors. Transfusion, 2008. 48(6): p. 1090-8.
  21. Shih, D.T., et al., Expansion of adipose tissue mesenchymal stromal progenitors in serum-free medium supplemented with virally inactivated allogeneic human platelet lysate. Transfusion, 2011. 51(4): p. 770-8.
  22. Su, C.Y., et al., Quantitative assessment of the kinetics of growth factors release from platelet gel. Transfusion, 2008. 48(11): p. 2414-20.
  23. Su, C.Y., et al., In vitro release of growth factors from platelet-rich fibrin (PRF): a proposal to optimize the clinical applications of PRF. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2009. 108(1): p. 56-61.
  24. Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules
  25. A. S. Wasterlain, H. J. Braun, and J. L. Dragoo, “Contents and formulations of platelet-rich plasma,” Operative Techniques in Orthopaedics, vol. 22, no. 1, pp. 33–42, 2012
  26. M. Tschon, M. Fini, R. Giardino et al., “Lights and shadows concerning platelet products for musculoskeletal regeneration,” Frontiers in Bioscience-Elite, vol. 3, no. 1, pp. 96–107, 2011
    • When talking about PLTs and their products, a great number of variables have to be considered. 
    • These variables are mainly related to PRP preparation methodsthe type of activatorsintra- and inter-species variabilitytypes of pathology to be treatedthe ways and times of administration and the association of PRP or PG with other treatments
  27. L. Andriolo, B. Di Matteo, E. Kon, G. Filardo, G. Venieri, and M. Marcacci, “PRP augmentation for ACL reconstruction,” BioMed Research International, vol. 2015, Article ID 371746, 15 pages, 2015.
  28. M. Del Fabbro, G. Gallesio, and M. Mozzati, “Autologous platelet concentrates for bisphosphonate-related osteonecrosis of the jaw treatment and prevention. A systematic review of the literature,” European Journal of Cancer, vol. 51, no. 1, pp. 62–74, 2015
  29. G. Filardo, E. Kon, A. Roffi, B. Di Matteo, M. L. Merli, and M. Marcacci, “Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 23, no. 9, pp. 2459–2474, 2015
  30. E. Lopez-Vidriero, K. A. Goulding, D. A. Simon, M. Sanchez, and D. H. Johnson, “The use of platelet-rich plasma in arthroscopy and sports medicine: optimizing the healing environment,” Arthroscopy, vol. 26, no. 2, pp. 269–278, 2010
  31. A. Roffi, G. Filardo, E. Kon, and M. Marcacci, “Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review,” 
  32. J. A. Textor, J. W. Norris, and F. Tablin, “Effects of preparation method, shear force, and exposure to collagen on release of growth factors from equine platelet-rich plasma,” American Journal of Veterinary Research, vol. 72, no. 2, pp. 271–278, 2011
  33. F. Vannini, B. Di Matteo, G. Filardo, E. Kon, M. Marcacci, and S. Giannini, “Platelet-rich plasma for foot and ankle pathologies: a systematic review,” Foot and Ankle Surgery, vol. 20, no. 1, pp. 2–9, 2014
  34. Y. Zhu, M. Yuan, H. Y. Meng et al., “Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review,” Osteoarthritis and Cartilage, vol. 21, no. 11, pp. 1627–1637, 2013
  35. T. E. Foster, B. L. Puskas, B. R. Mandelbaum, M. B. Gerhardt, and S. A. Rodeo, “Platelet-rich plasma: from basic science to clinical applications,” The American Journal of Sports Medicine, vol. 37, no. 11, pp. 2259–2272, 2009
  36. B. Di Matteo, G. Filardo, E. Kon, and M. Marcacci, “Platelet-rich plasma: evidence for the treatment of patellar and Achilles tendinopathy—a systematic review,” Musculoskeletal Surgery, vol. 99, no. 1, pp. 1–9, 2015.
  37. Heath Effects of Iron Overload and Benefits of Blood Donation (Travel to Health)
  38. Regenerative medicine: Current therapies and future directions
  39. Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA (2007) Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons. J Orthop Res 25(2):230–240
  40. Editorial Commentary: The Promise of Platelet-Rich Plasma
    • On the basis of this most recent Level I evidence review, PRP results in “significant clinical improvements” in patients with symptomatic osteoarthritis of the knee.
  41. Campbell, K.A., Saltzman, B.M., Mascarenhas, R. et al. Does intra-articular platelet-rich plasma injection provide clinically superior outcomes compared with other therapies in the treatment of knee osteoarthritis? A systematic review of overlapping meta-analyses. Arthroscopy. 2015; 31: 2213–2221