Enzyme Therapy (Neprinol) treatment of Dupuytren’s contracture

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The use of enzymes, like Neprinol, is an important topic for anyone with Dupuytrens contracture. Enzyme therapy (Neprinol, bromelain, nattokinase and serrapeptase primarily) is perhaps the most direct and specific internal therapy a person can use to attempt reversal of the contraction of tissue. DCI has never seen an effective and successful Dupuytrens contracture program that did not include the liberal use of enzymes to reduce and eliminate foreign protein in the form of contracted and dense contracted fibrous tissue.

 

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Description

An enzyme is a protein molecule that either starts or speeds up a chemical process without being used up or consumed in the process that it affects. Enzymes start or continue many thousands of complex chemical reactions that occur continuously throughout the body. They have been called “the fountain of life” because without them life could not exist.(1)

Dupuytrens contracture can be benefited by those systemic enzymes
that seek out and reduce foreign protein in the body

Enzymes working in your body at this moment got there in one of two ways:

1. Enzymes that come from within you – the supply you had at birth, or those you make from proteins already inside your body. There are just so many enzymes available to you from the start of life; you were born with just so many enzymes, and they will not last forever. It is estimated that by the time the average person reaches the age of 27 – 27 years old! – the body and health begin to decline because that is the usual halfway point of available enzymes supplied at birth. Sobering news, don’t you think? It is even more sobering to know some people are born with more and some are born with fewer enzymes available for their use. This can explain the variability of health and lifespan from one person to the next, no matter how well or how badly someone takes care of their body. Science is beginning to see that health and lifespan are largely determined simply by the supply of enzymes you have at the start of life. A person therefore is wise to protect the enzymes they have, (and pay attention to this next paragraph).2. Enzymes brought into your body from the outside – those supplied in whole or in part from the enzyme-rich foods that are eaten. Up to 40% of the proteins reorganized and rearranged in the body from dietary sources are used to produce more than 3,000 different enzymes found in the human body. Unfortunately, the enzyme content of food has significantly decreased due to overuse of soil, food processing, refining and preservation techniques, and a decreased consumption of fermented foods and fresh foods, which are high in enzymes.(2) This makes enzyme supplementation important to everyone, especially the person with Dupuytrens contracture.

Enzymes are critical to every aspect of life activity. Digestion is the first enzyme function that usually comes to mind. However, other enzyme dependent activities abound, such as energy production, brain function, elimination, detoxification, reproduction, muscle contraction, vision, cardiac activity, respiration, healing and repair, immunity and defense, and so on. We spend a lifetime using our enzymes to trigger every activity of life. Since they cannot be put back into the body as fast as they are being used, we deplete our reserve of enzymes as we get older. All the systems and functions that depend on enzymes – and that means all of them – sooner or later begin to weaken and falter: digestion becomes a problem; needing more rest than before; muscle mass declines; hearing, sight, and smell diminish; memory…memory… well, I forget what happens to memory. As enzymes become more rare, we experience what is called “getting older”.

Running low on enzymes affects fibrous tissue also. Enzymes circulate in the blood as part of the immunity and defense systems, to weaken and eliminate foreign invaders (bacteria and viruses) and remove foreign substances (cellular debris, blood clots, and other things that don’t have a good purpose in the body like unnecessary scar tissue). As enzyme levels get lower this defense function against fibrous tissue buildup begins to decline also. Here are examples of the inability to keep up with fibrous tissue buildup as we get older: Joints (knuckles, wrists, knees, etc.) get thicker and stiffen; the lens of the eye hardens (bifocals); heart valves stiffen (heart murmurs); tiny fibrous blood clots occur and arteries harden (circulation and blood pressure problems); muscles shorten (stooped posture), and so on. Throughout life fibrous tissue attempts to invade all areas, tissues and organs of the body, in a process called fibrosis. During youth the enzymes circulating in the blood keep this process in check, keeping you looking and feeling pretty good. With age there are fewer enzymes to remove the advancing army of fibrous infiltration, and slowly the fibrous tissue gains more and more territory in the body. Dupuytrens contracture can be seen as a part of the process of fibrous tissue buildup. It might begin earlier with some men, later in others, after injury in some men, without injury in others – but it happens.

DCI knows you have never read in any medical website a simple, common sense and broad explanation of Dupuytrens contracture that fits into the larger picture of life as the one you have just read. Think about it. This explanation gives you understanding and power over your Dupuytrens contracture. It becomes apparent there is another direction to take – enzyme therapy – toward controlling some of the fibrous tissue infiltration in your hand, as well as benefiting other areas and aspects of your general health.This section could easily be the longest of all since the topic of enzymes is so enormous. Hopefully we have explained this simple idea: Enzymes are necessary for every aspect of your life and health. As we get older and eventually run low on enzymes, problems start to occur like fibrous buildup in the body. Taking enzyme supplements should build up your reserve, supporting the innate ability to function at a healthier capacity.

What the Research Tells Us

The immense body of enzyme research done to this point has been focused on major problems of health and healing that have a wide and common interest to society — such as diabetes, cancer, Alzheimer’s disease, and many others. Little research effort appears to have been spent investigating a condition as relatively common as Dupuytrens contracture. Once again it will be necessary to take what is found about one condition or tissue and see how it applies to the problem of Dupuytrens contracture.In the opinion of DCI, nattokinase, serrapeptase, bromelain and papain are the four primary enzymes that demonstrate in research trials adequate ability to affect the fibrous material of the Dupuytrens contracture.

Nattokinase is an enzyme discovered in a traditional Japanese cheese-like food, called natto. It is made from boiled soybeans to which a friendly bacteria, Bacillus Natto, has been added. Natto has been used in Japan for over a thousand years as a folk remedy for heart and vascular diseases. While other soy foods contain other enzymes, it is only the natto preparation that was found to contain the specific nattokinase enzyme.

Dupuytrens contracture can be benefited by nattokinase since it singles out
the foreign protein of excess scar tissue in the body

Since its discovery, additional research has been done on nattokinase including 17 published studies in Japan and in the U.S. (3-19) The results have been very exciting because of the affect nattokinase has on improving circulation and how this affects the entire body – along with our speculation how this increased blood flow benefits Dupuytrens contracture. Healthy blood flow is the transport vehicle that delivers enzymes, nutrients, antibodies, and oxygen to every cell, regulates body heat, and removes waste products. Without good blood circulation true health is not possible. Among the enzymes that are depleted with age are those that constantly dissolve and remove small blood clots from the tiny capillaries all over the body. One of the enzymes that reduces and controls blood clotting is called plasmin, and it too diminishes over time. What makes plasmin important is that it can safely take apart or remove fibrin if it becomes necessary. Fibrin is a thread-like protein fiber that binds with several other elements in the blood to form an insoluble network, eventually becoming a blood clot. Sometimes you want a clot, and sometimes you don’t; the body knows the difference, but that is another story. Anyway, the connection of Dupuytrens to fibrin is this: before a scar becomes a scar it more closely resembles a clot with fibrin. If the fibrin gets out of hand because there is not enough plasmin to control the fibrin, the big mass of fibrin can turn into a large scar.

Purchase Nattokinase for Dupuytren contracture treatment
A second way in which nattokinase can help Dupuytrens contracture is by increasing blood circulation. An example of the ability of nattokinase to improve circulation comes from Biotechnology Research Laboratories and JCR Pharmaceuticals, Kobe, Japan.(21) They tested nattokinase’s ability to dissolve a blood clot in the carotid arteries of rats. Of the animals treated with nattokinase, on average they regained 62 percent of their blood flow, whereas those treated with plasmin regained just 15.8 percent of blood flow. More proof comes from JCR Pharmaceuticals, Oklahoma State University, and Miyazaki Medical College when they tested nattokinase on 12 healthy Japanese volunteers (6 men and 6 women, between the ages of 21 and 55). Volunteers were given 200 grams of natto (the food) before breakfast, then their ability to dissolve fibrin was determined through a series of blood tests. The tests indicated that natto increased the ability to dissolve blood clots: On average, the time it took to dissolve a blood clot dropped by 48 percent within two hours of treatment, and this ability to dissolve clots was retained for 2 to 8 hours. As a control, researchers later fed the same amount of plain boiled soybeans to the same volunteers and tracked their clot dissolving ability; this group showed no significant change.

 

Dupuytrens contracture sufferers find that Nattokinase 1500 is a powerful enzyme therapy
because it reduces foreign protein wherever it is found in the body

The benefit of nattokinase to increase circulation is real. Any potential healing and repair that should take place in a Dupuytrens contracture will be more likely to take place in the presence of a good blood supply to bring in all needed enzymes and nutrients, as well as to remove waste products.Nattokinase works to support healthy circulation in several important ways:
1. Nattokinase resembles plasmin, so it prevents fibrin from clumping in the blood. This keeps the blood “thinner”, or as the scientists would say “less viscid”. Blood that is thinner flows freer and easier, is less likely to clot, it makes for better circulation and all that a good blood flow can accomplish in the body.
2. Nattokinase resembles plasmin, so it can break down clots directly after they have formed. In fact, a study points out that the ability of nattokinase to break down a clot is actually four times greater than plasmin or elastin.(7, 11)
3. Nattokinase increases the natural production of the enzyme plasmin, which also helps to keep the blood thin, break down clots and other fibrous materials in the body.

How do you know if you might benefit from nattokinase? Here is a list of symptoms that suggest a reduction of blood in the body. See if you recognize yourself in this list. If you do, then perhaps nattokinase could be of great potential benefit to you.

1. Hands or feet, cold, numb, tingle
2. Thick skin on hands or feet (What does that sound like?)
3. Fingernails thin and break easily
4. Loss of physical stamina you once had; get winded easily
5. High blood pressure
6. History of cardiovascular disease
7. Memory not as good as it used to be

If you have any of these going on, you should consider adding nattokinase to your treatment plan.

Summarizing the benefits of nattokinase:

1. Supports normal circulation, blood flow, and blood viscosity (keeping it thin enough to flow well).
2. Supports normal blood-clotting mechanism directly via affect on fibrin fibers.
3. Supports normal blood-clotting mechanism indirectly via production of plasmin, which reduces fibrin fibers.
4. Maintains normal blood pressure levels by keeping fibrous material out of blood vessel wall and reduces small blood clots in capillaries.
5. Dupuytrens application: same effect on plasmin and fibrin are suspected to be beneficial on fibrous material of early scar development.

Dupuytrens contracture sufferers use Fibrozym because it is keyed
to reduce excess fibrous tissue wherever it is found in the body

Serrapeptase for Dupuytren contracture

This interesting enzyme comes from human-friendly bacteria known as Serratia E15, found in the gut of silkworms. Serrapeptase is used by the silk worm to dissolve the protein-based cocoon as it attempts to emerge as a moth. In humans, serrapeptase has been shown to act as an anti-inflammatory, anti-edema factor, and a pain-blocker in a large number of tissues, much like aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs).(20) Research indicates it may even help inhibit plaque build-up in arteries, thereby preventing atherosclerosis (hardening of the arteries) and resulting heart attack or stroke. For this reason serrapeptase has been called “the second gift from the silk worm.” The ability of serrapeptase to reduce fibrous tissue infiltration into blood vessels walls is the reason it is of interest to Dupuytrens. Unlike aspirin, this naturally derived enzyme does not cause ulcers and stomach bleeding.With no direct research into the effect of serrapeptase on Dupuytrens contracture or Peyronie’s disease, it is again necessary to compare and theorize the effect of serrapeptase in similar situations for possible benefit to Dupuytrens contracture.

Cystic Breast Disease Serrapeptase has also been used in the successful treatment of fibrocystic breast disease. The Dupuytrens connection is the chronic inflammation and development of fibrous tissue of the breast cysts. This fibrous tissue is similar to the type of tissue in scars and feels firm, thick, rubbery, and ridge-like, very much like Dupuytrens contracture and PD.

Purchase Fibrozym for Dupuytren contracture treatment

Trauma. In Germany and other European countries, serrapeptase is a common treatment for inflammatory and traumatic swellings, and much of the research that exists on this substance is of German origin. One study involved sixty-six patients who were treated surgically for fresh rupture of the lateral collateral ligament of the knee. On the third post-operative day, the group receiving serrapeptase exhibited a 50 percent reduction of swelling, compared to the controls. The patients receiving serrapeptase also became pain-free sooner than the controls, and by the tenth day, the pain had disappeared completely.(24)Hardened arteries Hans A. Nieper, M.D., noted Germany internist, studied the effects of serrapeptase on the formation of artery plaque (deposits of fatty substances, cholesterol, cellular waste products, calcium and fibrin, a clotting material in the blood). According to Dr. Nieper, only three 5 mg tablets of serrapeptase daily for 12 to 18 months are sufficient to remove fibrous blockages from constricted coronary arteries, as confirmed in many of his patients by ultrasound examination. He called serrapeptase a “miracle” enzyme because it digests non-living tissue, blood clots, cysts, arterial plaque (scar) and inflammation in all forms. However, the evidence to support serrapeptase’s role in preventing plaque build-up is anecdotal, since it remains unproven in the usual research sense. Still, further studies are called for in this area as Nieper’s research indicated that the protein-dissolving action of serrapeptase will gradually break down atherosclerotic plaques.(25) All of this has nice application to Dupuytrens contracture and PD.

Carpal Tunnel Syndrome This condition involves thickened and inflamed ligament tissue at the bend of the wrist, causing considerable pain and numbness of the hand and fingers. In this study, use of serrapeptase proved to be a useful alternative mode of conservative treatment.(26) (What does this sound like?)

Infection and Post-Operative Recovery There are many reasons to use serrapeptase after surgery. It is useful for the pain, inflammation and tissue response after tissue injury, as well as for its ability to assist recovery in a wide variety of traumas. (27-31)

Bromelain and Dupuytren treatment

Bromelain is a proteolytic (protein-digesting) enzyme of plant origin. Bromelain, also known as bromelin, is extracted from the flesh and stem of the pineapple plant, Ananas comosus. For years natives in the tropics have used this plant as a folk medicine.(32) More than eight protein-digesting components have been identified in bromelain.(33) Studies have shown the beneficial effects of bromelain in the treatment of inflammation and soft tissue injuries (34,35). These results suggest that bromelain can be useful in many conditions where soft tissue injury occurs.

More than other enzyme supplements, bromelain should be recognized for the one major ability that is not found in any other potential therapy that is so easily, readily and economically available to the person with Dupuytrens. Bromelain is unique among the protein digesting enzymes in its suspected capacity to stimulate secretion of collagenase. This particular enzyme, collagenase, is most important to Dupuytrens because mature and developing fascial cord and bands are primarily made of collagen. Collagen is degraded or digested by collagenase. And as was just stated, “bromelain is suspected to increase secretion of collagenase” that can take apart and remove the collagen material that makes up the major part of scar tissue. This is great news for the Dupuytrens sufferer! Bromelain increases the enzyme that takes apart the major building material of scar tissue.(38) That single bit of information should be enough to motivate a person with Dupuytrens contracture to jump out of his chair and order some protein-digesting enzymes, especially bromelain.

In addition, bromelain has several other abilities in relation to soft tissue healing: it inhibits clot formation, breaks down fibrous tissue,(37) reduces inflammation, and it has skin debridement (wound clearing) properties. Other less direct benefits are its ability to enhance absorption of drugs and nutrients, and to enhance the immune response to allergies. Bromelain is well absorbed orally and available evidence indicates that its therapeutic effects are enhanced with higher doses. Although all of its mechanisms of action are still not completely understood, it has been demonstrated to be a very safe and effective therapy. All in all, bromelain has many large, medium and small benefits for anyone with Dupuytrens contracture.

Enzymes product recommendation for Dupuytren treatment

Dupuytrens contracture sufferers like Neprinol because it combines all the best of the systemic enzymes
in one convenient product, removing and eliminating excess fibrous tissue wherever it is found in the body

Purchase Neprinol for Dupuytren contracture treatment

From research and investigation in this area, DCI realizes that not all enzyme products are equally effective. NEPRINOL® AFD is one of the best enzyme products DCI has found with sufficient potency and quality that it can be relied upon to treat the effects of Dupuytrens contracture. One of the industry standards is to measure enzyme potency or strength by “activity levels”. In measuring the ability to reduce fibrous tissue, this ability is expressed by “FU’s” or “fibrinolytic units”. Most enzyme products suggest a usual dose of 1-2 capsules at a time, providing an average of 1,000 – 2,000 FU’s. This is pretty much standard for the average enzyme product. Therefore, it would be wise to select an enzyme product on the basis of the FU’s it produces per dose, rather than the milligram weight per serving. NEPRINOL® AFD provides 15,000 FU’s per serving, yielding 133% higher activity levels. This is the reason DCI is really excited about NEPRINOL® AFD.

Soy Free Neprinol-AFD can assist the body to reduce scar tissue buildup, fibrosis, arthritic conditions, pain, swelling, inflammation and hundreds of other ailments. NEPRINOL’s formulation is more complete and essential than a daily vitamin. Replace the enzymes that Mother Nature removes as we age. NEPRINOL® is radically more advanced than today’s leading systemic enzyme blends. NEPRINOL® contains several sources of anti-oxidant fighting ingredients, as well as the full spectrum of proteolytic (protein digesting) enzymes, enterically coated to adapt to a wide spectrum of pH levels. NEPRINOL’s exclusive formulation contains several highly concentrated digestive enzymes that enable the body to digest fats, proteins, carbohydrates and sugars. These digestive enzymes convert the food we eat into energy rather than stored fat.NEPRINOL® AFD is the most scientifically advanced broad spectrum enzyme blend available. NEPRINOL® AFD uses individually enterically coated enzymes to increase pH range and resistance to stomach acid. NEPRINOL® AFD is the first systemic blend with 100% pharmaceutical grade components and the purest form of Serrapeptase, Nattokinase and CO-Q10 available. Several years of scientific research and clinical studies have been conducted on each and every component that makes up NEPRINOL® AFD. For the first time ever, you can get all of these enzymes in one powerful product.

NEPRINOL® AFD contains three primary ingredients, a well as several others that serve in a supporting capacity, that function to reinforce the stores of the enzyme system of the body. Serrapeptase to break down fibrin within the body and modulate the immune system, Nattokinase to improve cardio-vascular health and help eat away arterial plaque, and finally CO-Q10 regarded as one of the most potent and effective antioxidants available. CO-Q10 will fight free radicals and aid in reducing stress on the heart.

Notice that the cost for a bottle of NEPRINOL® is higher than some of the other enzyme products, but this is because it is more concentrated and comes in a larger size bottle than most. On a cost per capsule and cost per “FU” NEPRINOL® is a less expensive than all others.

Do not take NEPRINOL® without the consent of your physician if you are currently taking anti-coagulants or you are pregnant or lactating (as these subjects have not yet been tested).

Nattokinase – For those looking for a pure, potent source of nattokinase without having to travel to Asia, look no further!  Nattokinase 1500 from Douglas Labs provides a whopping 1500 fibrin units (FU) of nattokinase per serving.

For over 50 years the German company, Wobenzym, has studied and published more material than any other enzyme manufacturer in the world. Their signature product, WobenzymN, is said to be “the single-most researched enzyme product” in the world. If any company understands the benefits and mechanisms of enzyme therapy, this is the one. Of all the companies who produce enzyme products in the world, Wobenzym is the standard by which others are measured. With that kind of research and product development ability, you can rest assured that their Nattokinase 1500 product is an outstanding product.

We recommend this product because of the reputation and integrity of the Wobenzym name, and their huge commitment to product research. Dr. Sumi, discoverer of the nattokinase enzyme recommended a dosage of 2,000 fibrin units of nattokinase a day. Nattokinase 1500 has, as the name suggests, 1,500 fibrin units per two tablets, making this a simple and easy requirement to reach. We have found no other product that matches this one for supplement strength and value.

Fibrozym – Fibrozym contains Serrapeptase, Bromelain and Papain — a powerful trio of enzymes that can be especially beneficial to the reduction fibrous and scar tissue in the body.
Comprised of a hypo-allergenic, high-purity strain of serrapeptase, and plant-based bromelain and papain enzymes, Fibrozym normalizes the inflammatory response and improves overall tissue health. In addition it contains a high potency bromelain and bromelain to compliment and increase its fibrous-tissue busting ability. DCI has not found another product that combines Serrapeptase, Bromelain and Papain in such a high potency formula; this makes Fibrozym a unique and powerful addition to your Dupuytrens therapy program .
Unlike other products, Fibrozym is an enterically coated table, allowing it to pass through the stomach without being digested or degraded . Other non-enterically coated products, which get digested in the stomach, become less effective once they finally reach the bloodstream.Wobenzym introduced at the end of the summer of 2004 a new product called Fibrozym, that is their “fibrinolytic enzyme for tissue well being”. Fibrozym has ten times the amount of serrapeptase activity than their closest competitor, Vitalzym and Zymitol. It is coupled with an effective dosage of bromelain, papain and other support to create what we think is an outstanding product. Fibrozym supplies in heavy therapeutic dosage of the enzymes (serrapeptase, bromelain and papain) research has found to be so important for healthy tissue repair.

DCI thinks this is the product we have been waiting for.
With just these two products – Fibrozym and Nattokinase 1500 – it is possible to bring a world of enzyme benefit directly to your Dupuytrens treatment plan.

Dosage for Dupuytren treatment

Fibrozym – Three tablets three times daily for 1st month and then reduce to 3 per day, on an empty stomach. Absorption works best if there is no food (no digestion) taking place when you take this product. Therefore, take “on an empty stomach” means taking this product at least an hour before or two hours after eating. It is recommended you take Fibrozym for 3-4 months and then stop to evaluate further need. Fibrozym can be taken at a low dose, 1-2 per day, for health maintenance. Maximum: Up to 30 tablets per day only for acute trauma care for several days, until symptoms subside. Dosage this high not recommended for Dupuytrens.

Nattokinase 1500 – Two tablets three times daily, on an empty stomach. Absorption works best if there is no food (no digestion) taking place when you take this product. Therefore, take “on an empty stomach” means taking this product at least an hour before or two hours after eating. Many people take Nattokinase 1500 at a low dose, 1-2 per day, for health maintenance.

Neprinol – Because Neprinol is more concentrated it is advisable for some people to not start enzyme therapy with it, but to first use a bottle or two of Fibrozym or Nattokinase 1500 first to acclimate their body to the effects of this form of therapy.

For those using Neprinol it is preferable to slowly build up dosage, starting at 1-2 capsules twice a day (total of four daily).   As with Fibrozym and Nattokinase 1500, absorption works best if there is no food (no digestion) taking place when you take this product. Therefore, take “on an empty stomach” means taking this product at least an hour before or two hours after eating.

Do not attempt to take Neprinol, as good as this enzyme product is, as a solo or stand-alone therapy.  It works best when used as the central or key component of a larger therapy plan that creates a desirable synergistic effect for Dupuytren cord and nodule elimination.

For ideas and suggestions to put it all together, click Create a Dupuytrens Treatment Plan.

Dupuytrens contracture and Peyronie’s disease connection

There are many statistical and clinical similarities between Dupuytrens contracture and Peyronie’s disease. So much so, that there is even a connection between treatment that has benefited one condition being also potentially beneficial for the other. Because of this, it is common to learn from men who are being treated with a PDI therapy program for their Peyronie’s disease that their concurrent Dupuytrens contracture is also improving.

Therefore, when one therapy benefits Peyronies disease, it can be of interest to someone with Dupuytrens contracture.

Want to learn more technical information on this subject?

The sister organization for the Dupuytrens Contracture Institute (DCI) is the Peyronie’s Disease Institute (PDI). There are many statistical and pathophysiological similarities between these two conditions, that the same group of doctors who created PDI have also developed DCI. Many men who have Peyronie’s disease note that their Dupuytrens contracture also improves. Therefore, there appears to be a natural confluence of interest between these two problems. What can be said for one problem can be said of the other, especially in terms of treatment.

Order enzymes

1. Lopez, D.A. Willims, R.M. Miehlke, M. Enzymes: The Fountain of Life: Neville Press, Inc. Charleston, SC. 1994. ISBN: 1-884303-00-5

2. Hermann Von Wimpffen, H. Pecher, M.O. Enzymes: A drug of the future. Ecomed: AG & Co. www.ecomed.de ISBN: 3-609-51280-6

3. Liu BY, Song HY. [Molecular cloning and expression of Nattokinase gene in Bacillus subtilis] Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002 May;34(3):338-40. [Article in Chinese] Department of Molecular Genetics, School of Medicine, Fudan University, Shanghai 200032, China. hysong@shmu.edu.cn

4. Urano T, Ihara H, Umemura K, Suzuki Y, Oike M, Akita S, Tsukamoto Y, Suzuki I, Takada A. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis Cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem. 2001 Jul 6;276(27):24690-6. Department of Physiology, Hamamatsu University School of Medicine, 3600, Handa-cho, Hamamatsu, 431-3192, Japan.

5. Chang CT, Fan MH, Kuo FC, Sung HY. Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1.J Agric Food Chem. 2000 Aug;48(8):3210-6. Department of Food and Nutrition, Providence University, Shalu, Taiwan, Republic of China.

6. Kim W, Choi K, Kim Y, Park H, Choi J, Lee Y, Oh H, Kwon I, Lee S. Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang.Appl Environ Microbiol. 1996 Jul;62(7):2482-8. Department of Biotechnology, Institute of R & D, Yangpyung-Dong, Youngdeungpo-Gu, Seoul, (South) Korea.

7. Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat.Biol Pharm Bull. 1995 Oct;18(10):1387-91. Biotechnology Research Laboratories, JCR Pharmaceuticals Co., Ltd., Kobe, Japan.

8. Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K, Nishimuro S. Transport of nattokinase across the rat intestinal tract.Biol Pharm Bull.1995 Sep;18(9):1194-6. Biotechnology Research Laboratories, JCR Pharmaceuticals Co., Ltd., Kobe, Japan.

9. Fujita M, Nomura K, Hong K, Ito Y, Asada A, Nishimuro S. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1340-7. Biotechnology Research Laboratories, JCR Pharmaceuticals Co., Ltd., Kobe, Japan.

10. Suzuki Y, Kondo K, Matsumoto Y, Zhao BQ, Otsuguro K, Maeda T, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.Life Sci. 2003 Jul 25;73(10):1289-98. Dept of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu City, Shizuoka 431-3192, Japan.

11. Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura K. Dietary supplementation with fermented soybeans suppresses intimal thickening. Nutrition. 2003 Mar;19(3):261-4. Department of Pharmacology, Hamamatsu University School of Medicine, Shizuoka, Japan.

12. Tetsuya Hayashi, Chieko Takahashi, Yuji Kikuchas, Japan Functional Food Research Association, Department of Physiological Chemistry, Kurashiki University of Science and the Arts, Kurashiki, Okayama 712-8505, Japan Received May 6, 1998; Accepted October 5, 1998

14 Ozawa, K. (1994). Effect of natto bacillus on the intestinal microsystem. In “Basic and Clinical Aspects of Japanese Traditional Food Natto,” Sumi, H. Japan Technology Transfer Association, Tokyo, pp. 113-118.

15. Sumi, H, Sasaki, K. Oral administration of urokinase. 17th Int. Congr. Hematology, Paris, abstr. p.327, 1978.

16 Sumi, H. Toki, N. Sasaki, K. Robbins, K. Oral administration of urokinase. Thrombi. Res. 20:711-714, 1980.

17. H.Sumi,H.Hamada, ,H.Tsushima,H. Mihara and H.Muraki. A novel fibrinolytic enzyme(nattokinase)in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet Department of Physiology, Miyazaki Medical College, Miyazaki 889-16(Japan), Department of Fundamental Natural Science, Okayama University of Science,Okayama 700(Japan),and Department of Fermentation Technology, Faculty of Engineering, Yamanashi University, Kofu 400(Japan), 23 June 1986

18. H. Sumi, H. Hamada, H. Mihara, K. Nakanishi*, H. Hiratani*. Fibrinolytic Effect of the Japanese Traditional Food “Natto” (Nattokinase) Dept. of Physiology, Miyazaki Med. College, Miyazaki, Japan and Biochemistry Research Labo*. of JCR Pharmaceuticals Co., Ltd., Kobe, Japan

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