System Saver provides a superior way to manage the arthritic dog and to provide preventive maintenance for the healthy, sound dog.
The System Saver Difference: Unlike other joint health supplements, System Saver was designed by a veterinarian to employ the animal’s intrinsic regulatory systems to control excessive inflammatory, immune and degenerative enzyme activity. Normal activity of these systems permits a return to or maintenance of the normal healthy state.
System Saver has proven to be safe and effective and provides an alternative to NSAIDS, steroids and TNF-alpha inhibitors. The ingredients have undergone extensive scientific investigation and have demonstrated anti-inflammatory activity, MMP inhibitor activity and antioxidant activity.
Arthritis results from damage to the cartilage within the affected joint. Whatever the cause the result is inflammation (heat, swelling, redness, pain, loss of function) and increased activity of cartilage destruction by enzymes (metalloproteinases) released into the joint. In the undamaged, healthy joint, these enzymes are at work at a normal rate. Cartilage is regularly degraded and rebuilt anew from nutrients provided by a healthy diet. If, however the rate of degradation exceeds the rate of repair, degenerative joint disease (osteoarthritis) results. This increased enzymatic activity occurs because of "wear and tear" on the joint from aging, genetic disease (hip or elbow dysplasia, OCD), autoimmune disease, obesity, athletic injuries or traumatic injuries.
Until now, helping maintain a healthy balance between cartilage degradation and repair has not been an option, since metalloproteinase enzyme inhibitors were not commercially available. With the development of System Saver, this balance can be encouraged by inhibiting excessive enzymatic tissue destruction.
If your dog is already suffering from arthritis, hip dysplasia, OCD, elbow dysplasia or related ailments System Saver provides safe, effective anti-inflammatory activity to provide relief from pain, swelling and loss of function. These actions are accomplished in a plant -based formula without undesirable side effects.
Joint protection by System Saver is unlike that provided by any other supplement. Most supplements contain nutrients needed to rebuild damaged cartilage and large molecules that are building blocks for cartilage repair. System Saver takes a different approach. It intervenes before cartilage damage occurs by supporting the intrinsic regulators of the enzymes (metalloproteinases) responsible for cartilage destruction. This approach allows regenerative processes to prevail over degenerative processes and permits a return to the normal, healthy, sound state.
System Saver provides a revolutionary new way to protect joints from degenerative joint disease. Our one of a kind formula induces innate systems to intervene before damage is done rather than just providing nutrients to repair damage. But System Saver does more!
By enlisting the regulatory systems that control excessive immune, inflammatory and degenerative activity, it helps maintain the animal's overall health and provides outstanding support for the aging animal.
Hip dysplasia is descriptive of a conformational abnormality with a genetic basis. The anatomical abnormality is only that; it, in itself, is not arthritis. Secondly, if the cycle of inflammation and cartilage degradation did not occur, neither would osteoarthritis. So if a dog has the conformational problem without clinical signs, we need to concentrate on the opportunities for intervention in the progression of arthritis associated with hip dysplasia. Since cartilage repair is a relatively slow process (as cartilage tissue does not have a very good blood supply), this makes the preferred point for intervention to be inhibition of enzymatic cartilage destruction before it occurs. System Saver’s all natural metalloproteinase enzyme inhibitors do just that. This, along with its’ broad-spectrum anti-inflammatory activity, provides the ideal method for intervening in the chronic cycle of inflammation and cartilage damage we see in hip dysplasia associated arthritis.
What is hip dysplasia?
Hip dysplasia is a genetic condition resulting in abnormal conformation of the hip joint. The hip is a ball and socket joint, in which, normally the ball is deeply inserted in the socket resulting in a stable association. In hip dysplasia the ball is not deeply and tightly held in place because the socket is shallow. This results in a loose unstable fit. In addition the two surfaces are not matching or congruent, resulting in abnormal surface wear and tear as the joint moves.
Why does it make dogs lame?
The joint undergoes a series of reactions that result in clinical signs of arthritis showing up usually by 18 months of age. The joint cartilage and joint capsule become degraded and inflamed as a result of the abnormal wear and tear. This involves the activation of inflammatory chemicals and tissue destructive enzymes (metalloproteinases). The joint inflammation and cartilage degradation make the joint even more unstable yielding further upregulation of inflammatory and enzymatic activity. The enzymes also result in the activation of more inflammatory mediators. As you can see this cycle of joint damage, inflammation and the resulting pain is a self-perpetuating process, and the joint becomes less able to resist additional damage. The joint suffers degradation due to the abnormal wear and tear, and may not support the body weight as intended. The bones of the joint may also develop osteoarthritis which further degrades the joint.
If your dog is symptomatic: stiffness, less active, stopped running, jumping, climbing stairs
When the joint experiences cartilage damage, it is continually repairing itself and laying down new cartilage. While subjected to the stresses of hip dysplasia and the cycle of inflammation/enzymatic destruction this attempt at regeneration is overwhelmed by the degenerative process. System Saver inhibits both the inflammatory component and the enzymatic destruction of the joint-providing relief from pain while allowing the normal regenerative process to prevail.
If your dog has dysplastic hips but is not yet symptomatic
The summary above makes two important points. First, hip dysplasia is descriptive of a conformational abnormality with a genetic basis. The anatomical abnormality is only that- it, in itself, is not arthritis. Secondly, if the cycle of inflammation and cartilage degradation did not occur, neither would osteoarthritis. So if a dog has the conformational problem without clinical signs, we need to concentrate on the opportunities for intervention in the progression of arthritis associated with hip dysplasia. Since cartilage repair is a relatively slow process (as cartilage tissue does not have a very good blood supply), this makes the preferred point for intervention to be inhibition of enzymatic cartilage destruction before it occurs. System Saver’s all natural metalloproteinase enzyme inhibitors do just that. This, along with its’ broad-spectrum anti-inflammatory activity, provides the ideal method for intervening in the chronic cycle of inflammation and cartilage damage we see in hip dysplasia associated arthritis.
When the immune and inflammatory systems fail to respond to the signals intended to govern their response, the host suffers an autoimmune, hyper immune, hypersensitivity or chronic inflammatory disease. A prime example of this is found in cases of chronic dermatitis that persist although the inciting cause (parasite, fungus, bacteria, etc.) has undergone treatment. Many forms of frustrating dermatitis fail to respond to treatment until the intense; out of control inflammatory response is subdued with steroid therapy. System Saver provides a safe, effective alternative to corticosteroids and their negative side effects. System Saver implements the intrinsic regulators of these systems to curb the excessive reaction permitting a return to the normal, healthy state. System Saver is safe to use for life to provide for the management of chronic incurable conditions such as chronic dermatitis, rheumatoid arthritis, atherosclerosis, psoriasis, inflammatory bowel disease, cancer, autoimmune disease, lupus, fibromyalgia, coronary artery disease, type II diabetes, inflammatory airway disease (COPD), asthma, immune mediated allergic reactions and more.
When the immune and inflammatory systems fail to respond to the signals intended to govern their response, the host suffers an autoimmune or chronic inflammatory disease. System Saver curbs this excessive reaction permitting a return to the normal, healthy state. System Saver is safe to use for life, to help manage chronic incurable conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, lupus, pernicious anemia, or type 1 diabetes to name a few.
The immune system and immune response actually consist of two systems. Innate and acquired immunity are the two systems involved in protecting the body from foreign invaders. Acquired immunity results from recognition of an agent that is ‘not self’ and developing antibodies to this foreign agent. This initiates a sequence of defensive events many of which originate in the innate immune system. These include an influx of cells and chemicals designed to neutralize the invader and result in the inflammatory response.
Sometimes the system malfunctions, and the distinction between ‘self’ and ‘not self’ fails. The consequence is an immune response against the host’s own tissue, or autoimmune disease. This results in chronic inflammation and tissue damage to the host. Depending on which tissue is attacked this can manifest as rheumatoid arthritis, psoriasis, inflammatory bowel disease, lupus, pernicious anemia, or type 1 diabetes to name a few.
Until now, treatment has primarily involved suppressing the immune/inflammatory response with corticosteroids, which had undesirable and dangerous side effects. Recently it was discovered that a specific molecule (TNF) in cells is the ‘master regulator’ of the immune/inflammatory response, and this became a target for controlling these out of control reactions. New treatments designed to neutralize TNF are effective, but expensive, and, like corticosteroids are fraught with side effects. System Saver provides an alternative in the form of a natural, plant sourced, TNF inhibitor with the added benefits of inhibiting inflammation and tissue destructive enzymes - all safely and effectively.
Chronic Inflammatory Disease
When the immune and inflammatory systems fail to respond to the signals intended to govern their response, the host suffers an autoimmune, hyper immune, hypersensitivity or chronic inflammatory disease. System Saver directs the intrinsic regulators of these systems to curb the excessive reaction permitting a return to the normal, healthy state. System Saver is safe to use for life, to help manage chronic incurable conditions such as chronic dermatitis, rheumatoid arthritis, atherosclerosis, psoriasis, inflammatory bowel disease, cancer, autoimmune disease, lupus, fibromyalgia, coronary artery disease, type II diabetes, inflammatory airway disease (COPD), asthma, immune mediated allergic reactions and more.
Biological and biochemical factors, not time, cause the changes associated with aging. System Saver safely and effectively helps mitigate a number of these factors (increased inflammation, tissue destructive enzymes, oxidative stress) thereby permitting successful aging with a better quality of life.
Age related diseases are the result of the cumulative damage to tissues over a lifetime. When young, the balance between tissue degradation and tissue repair tilts heavily in the favor of regeneration. Most of us first begin to notice the age-related decline in tissue function when we’re in our forties or fifties. Our geriatric pets exhibit signs we associate and accept as the unavoidable consequences of aging. Collectively, these signs result in a state of frailty.
System Saver contains all natural plant sourced metalloproteinase inhibitors,TNF-alpha inhibitors, anti-oxidants and anti-inflammatories. These combined activities mitigate tissue destruction, chronic inflammatory disorders, oxidative stress and acute inflammation, which are some of the major contributors to aging. TNF-alpha has been implicated as the molecule that makes dogs “feel sick” when dogs are sick. TNF-alpha levels also increase with age or chronic inflammation, making you “feel old and tired”. Owners of older animals invariably report that their dogs act and feel years younger due to the multiple areas targeted by System Saver. Mobility and behavior show dramatic improvement.
System Saver's unique dual action mechanism induces the intrinsic regulatory systems to inhibit chronic inflammation, as well as tissue degeneration and as result is effective at restoring health as well as being the best preventive maintenance choice.
System Saver contains all natural ingredients that have been shown to contain metalloproteinase inhibitors, TNF-alpha inhibitors, anti-inflammatories and anti-oxidants. These combined activities mitigate tissue destruction, chronic inflammatory disorders, oxidative stress and acute inflammation.
System Saver's formula is the only source of all natural broad-spectrum metalloproteinase enzyme inhibitors. By regulating these tissue destructive enzymes, this formula limits damage done to cartilage and other tissue during athletics, repetitive activity, and aging.
These same enzymes are also responsible for activating the biochemical mediators involved in many chronic inflammatory disorders. By regulating these enzymes, System Saver has proven effective in the management of many of these conditions.
Unlike nutraceuticals (chondroitin, glucosamine, hyaluronate), System Saver inhibits tissue destructive enzymes, rather than just providing nutrients for repairing the damage.
MATRIX METALLOPROTEINASES (MMPS) AND TISSUE DEGENERATION
MMPs have, as their targets, molecules found in cartilage, bone, ligament, blood vessels, nerve matrix, lung matrix, bronchi, lamina and the extra-cellular matrix. These MMPs are involved in the ongoing remodeling of these structures. Regeneration is supported by providing a supply of building blocks and nutrients. When regeneration of these tissues is in balance with their degradation, a healthy steady state exists.
Factors such as aging (wear and tear), trauma, repetitive stress, athletic activity, exogenous toxins and endogenous free radicals induce and upregulate MMP production. This increases tissue destruction, inflammatory processes and induction of more MMP synthesis. As this cycle amplifies and perpetuates itself, the regenerative process is overwhelmed and tissue destruction and degeneration occurs.
System Saver's MMP inhibitory ingredients can intervene in this chronic vicious cycle and allow restoration of the balanced healthy state. Unlike nutraceuticals, System Saver acts on the degenerative processes before the destruction occurs.
When used regularly, the regenerative processes can dominate the degenerative, thereby slowing the damage from aging, repetitive stress (occupational or exercise induced) and other insults.
MATRIX METALLOPROTEINASES (MMPS) AND CHRONIC INFLAMMATORY CONDITIONS
Certain MMPs have pro-inflammatory molecules as their targets. Their action activates these pro-inflammatory molecules into bioactive inflammatory mediators. MMPs 2,3,7,9 and TNF attract and recruit inflammatory cells (monocytes, macrophages and neutrophils) to an area of inflammation by activating chemical attractants called chemokines (KC, fractalkine and TGFbeta).
These inflammatory cells contain inflammatory mediators (cytokines) and pro-TNF. MMPs then activatepro-TNF to TNFalpha-a very powerful cytokine that not only is inflammatory in nature, but also stimulates the production of more MMPs thereby amplifying a chronic vicious cycle of inflammation.
System Saver's ingredients intervene in this process by inhibiting MMPs thereby slowing inflammatory cell infiltration and cytokine and TNF production. This disrupts the cycle of inflammation common to many chronic incurable disorders such as rheumatoid arthritis, atherosclerosis, psoriasis, inflammatory bowel disease, aortic valve stenosis, cancer autoimmune disease, lupus, fibromyalgia, coronary artery disease, type II diabetes and more.
Chronic inflammation can also mean the difference between aging successfully and aging poorly. 'Chronic systemic inflammation is an underlying cause of many seemingly unrelated, age-related diseases. This fact is often overlooked by the medical establishment, yet persuasive scientific evidence exists that correcting a chronic inflammatory disorder will enable many of the infirmities of aging to be prevented or reversed.'32
Our geriatric pets exhibit signs we associate and accept as the unavoidable consequences of aging. Collectively, these signs result in a state of frailty.
System Saver's ability to support natural intrinsic regulation of inflammatory cytokines can help them avoid or minimize the devastating effects of chronic inflammation and age well.
Boswellia serrata (Frankincense)
The boswellic acids are the major active constituents. These compounds have been found to inhibit a number of pro-inflammatory and cell signaling pathway chemicals and cytokines involved in chemotaxis, increased vascular permeability and brochoconstriction. They also are inhibitors of matrix metalloproteinases(MMPs), which play a major role in cartilage destruction and tumor invasion and metastasis. In addition, they inhibit human leukocyte elastase (HLE), which has been implicated in the development of asthma, cystic fibrosis, chronic bronchitis & emphysema.
Studies have demonstrated the efficacy of Boswellia extract in asthma, chronic bronchitis, arthritis, rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn's disease and cancer chemo-prevention.*
Citrus reticulata (mandarin orange)
Is a source of the bioflavonoids of the class polymethoxylated flavones. Included in this class are nobiletin, tangeretin & others.
Recent studies on the polymethoxylated flavone components of orange peel have demonstrated a host of activities with preventive and therapeutic potential relevant to a number of conditions. These conditions include: arthritis, inhibition of enzymatic cartilage destruction, asthma and COPD, inflammatory conditions (acute and chronic), hyperlipidemia (lowers serum lipids), high cholesterol and LDL, hyperglycemia (glucose homeostasis), insulin resistance, heart disease, varicose veins, capillary permeability, Alzheimer's disease and Hepatitis C.
Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their ability to modify the body's reaction to allergens, viruses, carcinogens, microbes & inflammation.
Like the curcuminoids, flavonoids have matrix metalloproteinase (MMP) inhibitory activity, which helps relieve chronic inflammation and inhibit cartilage destruction and tumor invasion(metastasis).*
Curcuma longa (Turmeric)
as been the subject of much research and evaluation of its bioactive properties. The main bioactive constituents of Curcuma are curcuminoids.
Research has demonstrated anti-inflammatory, anti-oxidant, anti-viral, chemo preventive (early pre-cancer) and anti-cancer activities, as well as molecular biological action such as matrix-metalloproteinase(MMP) inhibitory activity. MMPs are responsible for cartilage destruction and are involved in perpetuating the chronic cycle of inflammation found to underlie many incurable chronic inflammatory diseases.
Curcumin's anti-inflammatory action is exerted at several sites along the inflammatory pathway and is the result of several diverse mechanisms acting in concert (see studies section).
Curcumin has demonstrated efficacy in relieving symptoms of arthritis as well as inhibiting the joint destructive activity of MMPs on cartilage.
Curcumin has demonstrated chemo preventive activity against colon, duodenal, fore-stomach, mammary, leukemic, pancreatic, and oral and skin cancers.
Curcumin has been shown to support cardiovascular health and most recently, has been investigated and found to be efficacious in suppressing the symptoms of Type II diabetes, multiple sclerosis and Alzheimer's.*
Camelia sinensis (green tea)
Has been the subject of much scientific research recently. Originally this research concentrated on the high anti-oxidant activity present, and its health benefits were attributed to this feature. Anti-oxidants neutralize free radicals that damage cells and genetic material (DNA & RNA) and are involved in the aging process. Green tea's anti-oxidant activity is the result of the constituents known as polyphenols. The primary polyphenols are catechins and gallocatechins. Further research demonstrated that these compounds also possess anti-inflammatory, anti-cytokine and matrix metalloproteinase (MMP) inhibitory activity. These activities (inflammation, free radical damage, increased cytokine and MMP activity) are instrumental in the processes underlying an array of conditions including: heart disease, atherosclerosis, arthritis, cancer, cartilage destruction, asthma, colitis (IBD/Crohn's), insulin resistance, diabetes and chronic inflammatory diseases (rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis). Studies in these areas have shown the catechins and gallocatechins to be beneficial in these conditions. In addition, green tea has been shown to reduce elevated cholesterol levels, while increasing HDL (good cholesterol) levels.*
1 J Ethnopharmacol. 1993 Mar;38(2-3):113-9.Mechanism of antiinflammatory actions of curcumine and boswellic acids.Ammon HP, Safayhi H, Mack T, Sabieraj J.
2 Mol Nutr Food Res. 2008 Sep;52(9):987-94. doi: 10.1002/mnfr.200700259.Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory role for curcumin. Biswas S, Rahman I.
3 Int Immunopharmacol. 2007 Dec 15;7(13):1659-67. Epub 2007 Sep 14.Anti-inflammatory effect of curcumin involves downregulation of MMP-9 in blood mononuclear cells. Saja K, Babu MS, Karunagaran D, Sudhakaran PR.
4 J Agric Food Chem. 2008 Oct 22;56(20):9399-403. doi: 10.1021/jf801222h. Epub 2008 Sep 25. Anti-inflammatory activity of an orange peel polymethoxylated flavone, 3',4',3,5,6,7,8-heptamethoxyflavone, in the rat carrageenan/paw edema and mouse lipopolysaccharide-challenge assays. Manthey JA, Bendele P.
5 Life Sci. 2006 May 1;78(23):2689-96. Epub 2005 Dec 9. Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms. Wu YQ, Zhou CH, Tao J, Li SN.
6 Biochem Pharmacol. 2003 Jun 15;65(12):2065-71. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.Lin N, Sato T, Takayama Y, Mimaki Y, Sashida Y, Yano M, Ito A.
7 Curr Med Chem. 2006;13(28):3359-69.Boswellic acids: biological actions and molecular targets. Poeckel D, Werz O.
8 Biochem Pharmacol. 2007 May 1;73(9):1434-45. Epub 2007 Jan 7.Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: Implications for the treatment of osteoarthritis. Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A.
9 J Pharmacol Exp Ther. 2004 Feb;308(2):767-73. Epub 2003 Nov 4.Green tea polyphenol epigallocatechin-3-gallate (EGCG) differentially inhibits interleukin-1 beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes. Ahmed S, Wang N, Lalonde M, Goldberg VM, Haqqi TM.
10 Eur J Biochem. 2003 Jun;270(11):2394-403. Selective inhibition of ADAMTS-1, -4 and -5 by catechin gallate esters.Vankemmelbeke MN, Jones GC, Fowles C, Ilic MZ, Handley CJ, Day AJ, Knight CG, Mort JS, Buttle DJ.
11 J Nutr. 2002 Mar;132(3):341-6. Catechins from green tea (Camellia sinensis) inhibit bovine and human cartilage proteoglycan and type II collagen degradation in vitro.Adcocks C, CollinP,ButtleDJ. P,ButtleDJ.
12 Biochem Biophys Res Commun. 2008 Aug 22;373(2):181-5. Nobiletin, a citrus polymethoxy flavonoid, suppresses gene expression and production of aggrecanases-1 and -2 in collagen-induced arthritic mice. Imada K, Lin N, Liu C, Lu A, Chen W, Yano M, Sato T, Ito A.
13 J Rheumatol. 2000 Jan;27(1):20-5. A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts. Ishiwa J, Sato T, Mimaki Y, Sashida Y, Yano M, Ito A.
14 Photochem Photobiol. 1999 Feb;69(2):148-53. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Katiyar SK, Matsui MS, Elmets CA, Mukhtar H.
15 Arthritis Res Ther. 2003;5(2):94-103. Epub 2003 Feb 14. Aggrecanases and cartilage matrix degradation. Nagase H, Kashiwagi M.
16 Biochem Biophys Res Commun. 2008 Aug 22;373(2):181-5. Nobiletin, a citrus polymethoxy flavonoid, suppresses gene expression and production of aggrecanases-1 and -2 in collagen-induced arthritic mice. Imada K, Lin N, Liu C, Lu A, Chen W, Yano M, Sato T, Ito A.
17 Clin Exp Rheumatol. 2008 Jan-Feb;26(1):139-45. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Bondeson J, Wainwright S, Hughes C, Caterson B.
18 Planta Med. 2006 Oct;72(12):1100-16. Boswellic acids in chronic inflammatory diseases. Ammon HP.
19 Endocrinology. 2008 Jul;149(7):3549-58.Dietary curcumin significantly improves obesity associated inflammation and diabetes in mouse models of diabesity. Weisberg SP, Leibel R, Tortoriello DV.
20 Ann N Y Acad Sci. 2001 Apr;928:274-80. 2001 Apr;928:274-80.A new function of green tea: prevention of lifestyle-related diseases. Sueoka N, Suganuma M, Sueoka E, Okabe S, Matsuyama S, Imai K, Nakachi K, Fujiki H.
21 J Nat Prod. 1999 Mar;62(3):441-4. Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-alpha expression by human monocytes. Manthey JA, Grohmann K, Montanari A, Ash K, Manthey CL.
22 Clin Exp Rheumatol. 2002 Mar-Apr;20(2):221-4. The association of serum matrix metalloproteinases and their tissue inhibitor levels with scleroderma disease severity. Toubi E, Kessel A, Grushko G, Sabo E, Rozenbaum M, Rosner I.
23 Vasc Health Risk Manag. 2008;4(4):805-17. TNF-alpha-mediated inflammation in cerebral aneurysms: a potential link to growth and rupture. Jayaraman T, Paget A, Shin YS, Li X, Mayer J, Chaudhry H, Niimi Y, Silane M, Berenstein A.
24 Respirology. 2008 Nov;13(7):1014-21. doi: 10.1111/j.1440-1843.2008.01365.x. Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD. Chen Y, Chen P, Hanaoka M, Droma Y, Kubo K
25 Phlebology. 2008;23(2):85-98. doi: 10.1258/phleb.2007.007027. Mechanisms of varicose vein formation: valve dysfunction and wall dilation. Raffetto JD, Khalil RA.
26 J Virol. 2008 Sep;82(18):8978-85. doi: 10.1128/JVI.00314-08. Epub 2008 Jul 16. Matrix metalloproteinase 9 facilitates West Nile virus entry into the brain. Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E.
27 Am J Pathol. 2008 Jul;173(1):144-53. doi: 10.2353/ajpath.2008.080081. Epub 2008 Jun 13. Matrix metalloproteinase-8 facilitates neutrophil migration through the corneal stromal matrix by collagen degradation and production of the chemotactic peptide Pro-Gly-Pro. Lin M, Jackson P, Tester AM, Diaconu E, Overall CM, Blalock JE, Pearlman E.
28 Brain Res. 2008 Jun 12;1214:145-58. doi: 10.1016/j.brainres.2008.03.036. Epub 2008 Apr 1. Multiple expression of matrix metalloproteinases in murine neurocysticercosis: Implications for leukocyte migration through multiple central nervous system barriers. Alvarez JI, Teale JM
29 Ann Vasc Surg. 2007 May; 21(3): 392–401. Role of Matrix Metalloproteinase Inhibitors in Preventing Abdominal Aortic Aneurysm Faisal Aziz, MD1 and Helena Kuivaniemi, MD, PhD
30 J Invest Dermatol. 2008 Dec;128(12):2748-50. Induction of matrix metalloproteinase-9 in keratinocytes by histamine. Harvima IT.
31 Antioxid Redox Signal. 2013 May 10; 18(14): 1818–1892. Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases. Del Rio D, Rodriguez-Mateos A, Spencer J, Tognolini M , Borges G, Crozier A
32 Life Extension Magazine Jan, 2002. Chronic Inflammation – The epidemic disease of aging