Multiple sclerosis inflammation associated with

Over the last decade, it has become more and more widely accepted that inflammation, associated with dysfunction of metal ion homeostasis (Fe, Cu, and Zn) accompanied by concomitant oxidative stress, is a key factor in a large number of neurodegenerative diseases such as Alzheimer s disease, Parkinson s disease, Huntington s disease. Amyotrophic lateral sclerosis (ALS), multiple sclerosis, Friedreich s ataxia, and others (Crichton Ward 2006). Support comes from the observation that AD, PD, and many other neurodegenerative diseases are characterised by increased levels of some of these metal ions in specific regions of the brain. 

Inflammation is associated with various diseases such as rheumatoid arthritis, cancer, myocarditis, arteriosclerosis, bowel diseases, multiple sclerosis, asthma, and many others. While several inflammatory markers are commonly expressed during any inflammatory disorder, some are symptom specific. Therefore, the gene array data will be particularly helpful in indicating the appropriate disease model for subsequent preclinical and clinical tests. Only functional, active extracts with potentially safe and novel modes of actions may then be subjected to labor-intensive large-scale extraction, fractionation, characterization, and isolation of novel bioactive components. We believe that the strategy as described schematically in Figure 4.1 will allow efficient use of plant extracts and other natural resources toward identification of novel drug leads for human health care. 

In view of successful animal experiments (20 see also Chapter 14), a sustained-release dexamethasone device was implanted in one eye of a patient with bilateral severe uveitis associated with multiple sclerosis (20,21). The patient had previously undergone pars plana lensectomy and vitrectomy in the right eye for decreased vision associated with cataract. Despite chronic topical corticosteroids, the patient had persistent bilateral low-grade inflammation and recurrent severe bilateral iridocyclitis. Best corrected visual acuity was 20/400 in both eyes. Systemic corticosteroids and methotrexate controlled the intraocular inflammation but the patient was intolerant of these medications because of systemic side effects. The nondegradable dexamethasone device was inserted into the patient s left eye. 

The targeting of molecular markers associated with inflammation could, in principle, be useful for the imaging and therapy of several other inflammatory diseases. Besides rheumatoid arthritis, these include inflammatory bowel diseases (Crohn s disease and ulcerative cohtis), psoriasis, atherosclerosis, and diseases of the central nervous system (Alzheimeris disease, multiple sclerosis, etc.). 

Certain chronic diseases of the CNS (eg, cerebral palsy, multiple sclerosis, stroke) are associated with abnormally high reflex activity in the neuronal pathways that control skeletal muscle the result is painful spasm. Bladder and anal sphincter control are also affected in most cases and may require autonomic drugs for management. In other circumstances, acute injury or inflammation of muscle leads to spasm and pain. Such temporaiy spasm can sometimes be reduced with appropriate drug therapy. 

CCRl plays an important role in host defense and is involved in regulating the chemotaxis of immune cells, a feature it shares in common with all chemoldne receptors. Dysregulation of this response leads to autoimmunity and CCRl has been associated with the pathophysiology of a number of diseases including rheumatoid arthritis [7-9], multiple sclerosis [10-12], transplant rejection [13, 14] and allergic inflammation [15-17]. 

Paradoxically, considraing the essential benefits of NO, its overproduction leads to septic shock. Uncontrolled release may also be the cause of brain damage afta- a stroke and disorders such as Alzheimer s and Huntington s diseases. The occurrence of high levels of nitrite ion, NO2 (the product of NO oxidation), in the joints of people with rheumatoid arthritis indicates overproduction of NO as a response to inflammation. Similar associations have been established for schizophrenia, urinary disorders, and multiple sclerosis. The rapidly evolving story of NO is an example of how little we still know about the functions of the body, but also how rapidly a discovery leads to the evolution of an entire field. 

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