IMMUNOSUPPRESSANTS FOR TREATMENT OF RA (RHEUMATOID ARTHRITIS): AZATHIOPRINEImuranTablet size: 50 mgUsual dose: variableEffective within: six weeks to six monthsAzathioprine was initially introduced as a form of cancer chemotherapy and is still being used for that purpose. It is also used to prevent rejection in organ transplant recipients. It was the first immunosuppressant to be approved by the FDA for use in RA and has been shown to be an effective treatment. Many physicians prefer to reserve this therapy for patients who have not responded to treatment with other DMARDs. Azathioprine is a notable component in many combination therapies.
Side effects of azathioprine The side effect of most concern with azathioprine use is blood abnormalities, most commonly a lowered white blood cell count. Infection can result and can become severe when insufficient numbers of white blood cells are present to destroy infection-causing bacteria. As with other immunosuppressants, there is also an increased risk of unusual infections even without a change in the white blood cell count. Less common blood abnormalities include decreased numbers of platelets or red blood cells (resulting in anemia). With low numbers of platelets, bruising or bleeding may occur more easily. Blood abnormalities almost always improve when azathioprine is discontinued. Life-threatening situations are rare. Any person taking azathioprine must be monitored vigilantly by a physician who is an expert in immunosuppressant therapy.Another side effect that has received a great deal of attention is the risk of developing cancer after prolonged use of azathioprine. This concern is hotly debated in rheumatology circles. Findings from studies of large numbers of RA patients taking azathioprine in the United Kingdom are reassuring. These studies suggest that the additional risk of cancer, although it exists, in people taking azathioprine as compared with others with RA, is actually quite small.*99/209/5*

RHEUMATOID ARTHRITIS TREATMENT: QUESTIONS ABOUT NSAIDs, COX-2 DrugsCan the NSAIDs (non-steroidal anti-inflammatory drugs) ruin my kidneys?This is particularly true of people who have bad kidneys to begin with. The elderly, the dehydrated, and those taking drugs that cause dehydration are all at risk of encountering problems with these drugs. There is some evidence that the NSAIDs can lower the filtering capacity of the kidneys.
Are over-the-counter drugs different from those prescribed for me?No, the over-the-counter drugs are the same as the prescription agents, just at lower doses. Several years ago, it was decided that certain NSAIDs could be offered over the counter at a lower concentration. Unfortunately, this did nothing to lower the potential for abuse (some people take these like candy) or lower the incidence of bad effects. Ibuprofen (Advil, Nuprin, and others) has the potential for causing problems like ulcers in the stomach, perforation of the bowel, and bleeding if the directions for its use are not followed.
What is a COX-2 drug?This is a new class of NSAIDs. A COX-2 drug is one that selectively blocks cyclooxygenase-2 while leaving cyclooxygenase-1 alone. Before the discovery of COX-2 drugs, anti-inflammatories blocked both COX-1 and COX-2. While both of these enzymes play roles in inflammation, COX-1 also has several “housekeeping” roles in the body, including regulating normal cell function in the gastrointestinal tract and the blood. So blockage of this enzyme, while eliminating pain and inflammation, can cause harm to the intestinal wall over the long term. The mucous coating of the stomach is destroyed, and thus there is a great likelihood for the development of ulcers and major problems with gas and discomfort. You can even vomit blood or have black, tarry stools. It might be wise to look for these signs if you have to take large amounts of NSAIDs as a matter of course.There are only two COX-2-seIective drugs on the market: Celebrex (celecoxib) and Vioxx (rofecoxib).
How do the COX drugs affect the bowels?These drugs have both bad and good effects on the small and large intestines. COX inhibitors can cause diarrhea in some people; however, they can also reverse and destroy colon polyps and possibly prevent colon cancer itself. I would not be surprised if COX-2 inhibitors are prescribed for everyone in the future as a protective measure for bowel cancer, particularly if one has a relative with colon cancer.
So, these drugs can help me in cancer prevention?Yes. These drugs do some remarkable things that have just become obvious to scientists. They accelerate a process called programmed cell death (apoptosis). This acceleration speeds the death of malignant or potentially malignant cells. Currently, these drugs are the subjects of research in cancer of the colon, stomach, and breasts.
Do these drugs cause high blood pressure?All of the prostaglandin inhibitors, those agents that inhibit COX, can raise the blood pressure or in rare cases even lower it.*30/141/5*

It wouldn’t take long to produce a small quantity for some preliminary testing, but there were drawbacks. The original substance was effective as an injectable, but to make it readily available to the public, an oral form would have to be developed. As an orally administered product the original injectable form often produced diarrhea or upset the stomach. It was a heavy oil that resulted a gooey mess when put into capsules. Furthermore, not only was it difficult to digest, its bioavailability was very low. Low bioavailability results in very little of a product actually being assimilated in a form that’s effective for its purpose in the body. That means more product is needed to accomplish its mission. And that drives up the cost, which was already very high as a result of the complexity in producing the substance.

Once the decision was made to try to develop an improved product, the original researcher was approached with an offer to join in the forthcoming project. For reasons not clearly expressed, he refused. Perhaps, as a result of the previous rejections, he felt there was no commercial value to the substance. Or he may have had other considerations. Whatever the reason, he rejected the offer.

What the new researchers were after would have to be quite different from the original, yet retain or improve on its effectiveness. Thanks to the genius of the biochemist who found the journal article, all of their goals were met. He was able to develop a product with high bioavailability when taken orally. Furthermore, it did not upset the stomach. Nor did it disturb the intestinal tract, except in the very most sensitive persons. And he managed to overcome one of the biggest hurdles: come up with a manufacturing process that was cost-effective. It was an amazing feat.

*12\142\2*

Medical professionals are loathe to use the word miracle in the face of the most miraculous of circumstances. Nevertheless, the word keeps cropping up in physicians’ reports about CMO. Dr. William C. Douglas titled his article A New “Miracle Cure” for Arthritis in the newsletter Second Opinion. Dr. Douglas Hunt used the word in his book Boom You ‘re Well. And patients call it miraculous all the time. Even medical doctors who’ve sought relief from their own pain and suffering through various other remedies have used the expression liberally.

It’s no wonder, for there have been virtually no truly significant advances in the treatment of arthritis since the times when people were chewing on willow tree bark to suck out its aspirin, or later the synthesis of aspirin by the German chemist Felix Hoffman in 1893. Medical science has made virtually no progress in the treatment of arthritis in over a hundred years. Pain killers and anti-inflammatory drugs are all we’ve had, and those just try to help relieve the symptoms. There’s been absolutely nothing to treat the cause of arthritis. That is, not until now.

*10\142\2*

Cetylmyristoleate, the original oily substance that eventually led to our research and development of CMO Cerasomal cis-9-cetylmyristoleate™ for oral administration, is a natural substance. It was not deliberately created, it was discovered in nature. Myristoleates are known to occur naturally in trace amounts in certain fatty tissues of only a few animals: cows, sheep, chickens, whales, beavers, and mice-although there may be a few others. For humans they occur in minute amounts as natural food components in butter, cheese, beef, chicken, lamb, and mutton. They also occur as natural food components for predatory animals that feed on any of the animals or foods mentioned. Their role in nutrition has not been studied, but they have never been known to cause harm. CMO is a safe, nontoxic, naturally derived substance. Certified laboratory toxicology testing proves it. These scientific tests certify CMO is nontoxic in massive doses and causes no harmful side effects. CMO achieved the safest rating class awarded.

Because it is a natural substance and not one designed and created with a specific purpose in mind, the precise pharmacodynamics of CMO are not clearly evident as they would be in the case of a substance that had been designed in the laboratory. Therefore, its biochemical and physiological effects must be determined by scientific investigation, analysis, and

interpretation – not by a theory from which something has been specifically designed. Nevertheless, there is a strong foundation of scientific research concerning memory T-cells that gives us a basis of understanding regarding the mechanisms of action of CMO.

Cetylmyristoleate remained unnoticed for twenty years after its discovery until the research team of the San Diego International Immunological Center (SDC) unearthed it and developed it into a usable product (“CMO”) early in 1995. There is no known research on cetylmyristoleate pharmacodynamics, and certainly none that has ever been published.

However it has long been established scientifically that myristoleate analogs are found in the composition of cell walls of living organisms. We believe that’s what allows CMO to permeate the cell walls of memory T-cells to accomplish their mission. Our pharmacodynamic model of the immunomodulatory effects of CMO involves the naturally programmed functions of memory T-cells. Living cells of all kinds have a life-span or program that is predetermined by either time or function. Many cells are programmed to complete their life cycle according to a predetermined span of time. Others, like memory T-cells, are programmed to deactivate upon completing a specific function.

When the system errs it results in autoimmune or other problems that may result in ailments like arthritis, fibromyalgia, lupus, sarcoidosis, scleroderma, etc. – or the chronic inflammatory and autoimmune complications of other diseases like multiple sclerosis, emphysema, asthma, prostatitis, psoriasis, macular degeneration, tendinitis, sciatica, and others.

Remember, it’s the memory T-cells that are responsible for perpetuating autoimmune disorders. They are the military “Generals” of the immune system that direct immune cell activities.

When a memory T-cells completes its function it is supposed to deactivate. We have learned that some memory T-cells avoid programmed deactivation. Virgin (naive, or unprogrammed) memory T-cells are stable, but following activation they can be maintained in continuous cycle by periodic re-stimulation from macrophages or other memory T-cells.

Normally, activated T-cells become increasingly unstable with each cycle of activation and rest, and are less likely to accept further re-stimulation. This process limits T-cell memory by preventing the continuous cycling of primed cells. This is a very important limiting mechanism that is vital to the prevention of excessive memory T-cell populations.

Nevertheless, some programmed cells revert to the stable state and are indistinguishable from naive cells. This is vital to avoid the complete loss of important defensive programs in a correctly functioning immune system. An extremely close correlation exists between the resting/naive memory T-cell populations and the programmed populations.

Studies also reveal that in arthritics, the synovial fluid in the joints is over-populated with programmed memory T-cells – and they are very resistant to deactivation. Studies performed with patients and in lab experiments indicate that this results from interaction with certain joint tissue (stromal cells in the pannus tissue). Gout does not involve proliferating pannus tissue.

This supports our clinical findings that CMO has less effect on gout than on rheumatoid, osteoarthritis, and other forms of arthritis.

Many diseases resolve themselves. Arthritis and most other autoimmune ailments do not. Studies show that the persistent inflammation that is characteristic of rheumatoid synovitis and other autoimmune ailments results from the persistence of memory T-cell populations.

Unlike memory T-cells, which don’t engage in battle, other T-cells are directly combative. These sacrifice their lives to win. And at the end of an immune response the remaining excess cells are eliminated. It is a vital operation of the immune system. However, these cells still contain cytolytic molecules and are toxic. The spilling of some of these toxins may account for the mild Herxheimer (toxicity or “breakthrough pains”) reaction that sometimes occurs with the use of CMO.

This new perception of memory T-cell function has yielded insights into disease processes such as viral infection, rheumatoid arthritis, lupus and many others. Lupus produces a broad spectrum of autoantibodies to cellular components. Studies show that patients with lupus actually have very high levels of expired cytotoxic cells that have not been effectively cleared. Inadequate clearance of these cells following infections is the likely source of the antigens that trigger the autoimmune process. This is true for virtually all disorders with autoimmune components and clearly explains the value of CMO for such diseases.

Yet in periods of health the number of T-cells present remains relatively constant. Contrary to conventional belief, resting memory T-cells also require continuous signals to stay active. These signals are found in blood and in even greater amounts at sites of inflammation such as the rheumatoid synovium. Resting memory T-cells are graded in the same way as activated cells: naive cells are stable, early primed cells are less so, and highly active cells are very unstable. The levels of signal required are much greater for activated cells.

Also, memory T-cells maintained at high density in culture do not need external signals for survival. They seem to signal each other. This activating mechanism appears to be similar to the stromal cell influence on memory T-cells, and in part explains the stability and survival of excessive memory T-cell populations.

Obviously much more research is necessary to understand all the complex mechanisms of memory T-cells and CMO in the control of autoimmune diseases. Studies are also being planned to better understand how CMO impacts on other diseases. Clinical evidence already clearly indicates that CMO affects virtually any ailment with chronic inflammatory or autoimmune components.

It also indicates that autoimmune processes can be triggered by many factors encountered in everyday life events. Another chapter of this book deals with how CMO can nip those processes in the bud and prevent them from developing into troublesome, and sometimes crippling, degenerative ailments.

*8\142\2*

Chronic inflammatory processes such as those found in fibromyalgia, emphysema, lupus, Crohn’s disease, diverticulitis, irritable bowel syndrome, colitis, tendinitis, and many other ailments are also the result of faulty or detrimental autoimmune regulation. Autoimmune factors also play a role in diseases like myasthenia gravis, muscular dystrophy, cerebral palsy, post polio syndrome, Grave’s disease, autism, attention deficit disorder, asthma, allergy, and many others.

It has also been recently discovered that chronic inflammatory processes play a very significant role in many cardiovascular attacks and diseases.

*6\142\2*

Absolutely-regardless of whether it’s rheumatoid or osteoarthritis! However, there are no conventional pharmaceuticals that can safely alter the process that is causing the attacks against your cartilage. Nevertheless, quite fortunately, Mother Nature has provided one. We’ll get to that shortly.

One of the three pharmaceutical companies researching more creative approaches to the treatment of arthritis is working on a custom-made antibody that “can temporarily knock the immune cells out of commission.” The company claims that more than half of the 122 patients in one study showed “significant improvement without debilitating side effects.” That is further confirmation that intervening in the autoimmune process can affect the arthritic cycle. Article also concludes that none of the three drugs being studied can cure the disease: “When patients stop taking them, pain and stiffness return.”

Well, that certainly indicates some progress, but it was only a study and it’s going to take several years before anything trickles down to where something may become available to the public. When it does, it will prove to be prohibitively expensive for almost all but the wealthy or the fully insured. Furthermore, it may be years before you even hear of it again. And the side effects may be horrific.

Fortunately there’s no need to wait for help. Decades ago a researcher employed at the US National Institutes of Health discovered a substance that does all that the most advanced researchers today dare hope to accomplish – and morel The modern evolution of that substance is called CMO. And yes, it does interrupt the cycle of events and put a halt to the arthritic process with no harmful side effects. Furthermore, reports over the years indicate the benefits seem to be permanent. And it’s a product derived from purely natural sources. (Mother Nature triumphs again!).

Where has it been hiding all these years? The mystery shall unfold in the chapters that follow – along with full details of how it’s made, where it comes from, and how it evolved into a modern day miracle against arthritis. But first, it will be useful for you to learn additional information about the underlying autoimmune system processes that cause arthritis in the first place.

*4\142\2*