ganglia and other nervous tissues secrete a variety of hormonal ligands. There are undoubtedly more neurokines still to be discovered. Immune cells secrete a huge array of cytokines with a variety of e ects throughout the body. Many of these ligands are not fully understood. The kidneys, liver, pancreas, thyroid, adrenal glands, heart, vascular system, lymphatic system, reproductive organs, skin and other organs may also produce unknown extracellular ligands that are vital to proper health.

Drug development currently involves the carpenter approach: if the hammer does not work, get a bigger hammer. A good example of this approach is if aspirin does not work for rheumatoid arthritis, use methotrexate. Unfortunately, patients can die from improper use of methotrexate. A corollary of the carpenter approach is the search for more specific receptors. For instance, if antihistamines produce drowsiness by interacting with too many receptors (brain H1 and H2), find a more specific receptor (peripheral H1) that will not cause drowsiness. Similarly, if non-steroidal anti-inflammatory agents cause ulcers by interacting with too many receptors (Cox-1 and Cox-2), find a drug for a more specific receptor (Cox-2) that will not lead to ulcers. Unfortunately, the more specific receptor approach has resulted in catastrophic events with many thousands of people su ering major toxic e ects and death. Some of the peripheral H1 blockers caused arrhythmias. Some of the Cox-2 inhibitors caused thrombosis leading to heart attacks and strokes. Despite all of the powerful drugs available, there are no drugs that cure hypertension, heart disease, diabetes, arthritis and other chronic conditions. Currently available drugs can only manage these diseases. It is possible that finding drugs to re-establish the proper balance of agonist/antagonist and signal transduction networks may be a better approach. Better yet, promoting healthy lifestyles may help maintain or re-establish good health.

1.5 Toxic Lifestyles and Disease Treatment

Healthcare in the future will depend on helping people maintain proper lifestyles that promote a healthy balance of extracellular agonists and antagonists as well as signal transduction networks. Lifestyles are far more powerful than most drugs in terms of maintaining health, since lifestyle can alter many endogenous ligands and signal transduction networks at once. Commonly prescribed drugs tend to be magic bullets that a ect only one mechanism at a time. The magic bullet approach to drugs makes drugs far too specific and renders them useful only for managing one aspect at a time of a disease. However, drugs will always be needed to treat ill patients. Drugs that alter signal transduction pathways, such as protein kinase inhibitors, tend to have many e ects throughout the body. Some of these e ects are unwanted and therefore toxic. However, by using a model of matrix interactions that produces drug e ects, as presented above, it is possible that ways of decreasing toxicity may be found. Another approach may be to find drugs that help re-establish normal endogenous ligand synthesis and release.

For instance, a drug that stimulates endorphin synthesis and release may be useful in pain therapy.

There are four statements that patients want to hear. 1. You do not have to lose weight and exercise, because we have powerful drugs to control blood cholesterol. 2. You do not have to lose weight and exercise, because we have powerful drugs to control blood pressure. 3. You do not have to lose weight and exercise, because we have powerful drugs to control blood glucose. 4. You should not exercise, because exercise, especially running, causes arthritis. All four of these statements are false. Drugs that control cholesterol slow down, but do not stop, atherosclerotic processes. Heart attacks and strokes are delayed by drug therapy, but not prevented. Drugs that control blood pressure delay, but do not prevent, the onset of congestive heart failure. Drugs that control blood glucose delay, but do not prevent, the loss of vision, loss of toes, loss of kidney function and other consequences of diabetes. Exercise, especially

running, has been shown in several studies to slow down the progression of arthritis.13–16

Recommendations for lifestyle changes are not accepted readily by patients who are more interested in maintaining their toxic lifestyles, and adding drugs to manage their chronic conditions. In addition, healthcare professionals cannot make a living by teaching patients about healthy lifestyles. They make their livings by selling drugs and carrying out surgery. However, lifestyle changes are suggested for many chronic conditions, especially hypertension and diabetes. Patients are encouraged to lose weight, alter their diets, decrease sodium intake to no more than 2.4 g daily, stop smoking, decrease alcohol intake to no more than 15 ml (1 drink) daily for women or no more than 30 ml (2 drinks) daily for men, and to exercise. Among athletes, optimal body composition is about 4% body fat for men and 12% body fat for women. Women become amenorrheic and osteoporotic below 12% body fat. Optimal diets contain vegetables, whole grains and five servings of fruit daily. Recommended diets may have about 60% caloric intake from carbohydrate, 20% from protein and 20% from fat. Exercise should be moderate, not strenuous, and should be enjoyable. Walking, running, cycling, swimming and other forms of aerobic exercise are encouraged.17 Yoga, tai chi, meditation and spiritual practices are becoming popular among health-conscious adults and seniors. Patients may start with about 20 minutes of physical exercise daily and should increase this over a year or more to about an hour each day. Spirituality and its health e ects are poorly understood by science.18 Yet many patients seem to benefit from increased spirituality during their recovery processes. As mentioned in the discussion on migraine headache later in the book, a form of homeostatic regulation introduced by Bruce McEwen, known as allostasis, fits nicely into the holistic concepts introduced in this opening chapter.19 Daily physical exercise, meditation and spiritual practices should be maintained throughout life. The goals of lifestyle alterations are to maintain a productive personality, decrease abdominal fat, decrease osteoporosis, decrease inflammation of the joints, decrease blood cholesterol and glucose levels, decrease blood pressure and increase the exercise endurance of the heart.

References

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2.B. McEwen and E. N. Lasley, The End of Stress as We Know It, Joseph Henley Press, Washington, D.C., 2002.

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K.K. Parker, Neurochem. Int., 2007, 50, 109.

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7.Y. Matsuzawa, FEBS Letts, 2006, 580, 2917.

8.I. Matias and V. Di Marzo, Trends Endocrinol. Metab., 2006, 18, 27.

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10.A. G. Pittas, N. A. Joseph and A. S. Greenberg, J. Clin. Endocrinol. Metab., 2004, 89, 447.

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