Transverse myelitis (TM) is a rare neurological condition wherein the spinal cord is inflamed. The adjective transverse implies that the spinal inflammation (myelitis) extends horizontally throughout the cross section of the spinal cord; the terms partial transverse myelitis and partial myelitis are sometimes used to specify inflammation that affects only part of the width of the spinal cord. TM is characterized by weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Signs and symptoms vary according to the affected level of the spinal cord. The underlying cause of TM is unknown. The spinal cord inflammation seen in TM has been associated with various infections, immune system disorders, or damage to nerve fibers, by loss of myelin. As opposed to leukomyelitis which affects only the white matter, it affects the entire cross-section of the spinal cord. Decreased electrical conductivity in the nervous system can result. Signs and symptoms
Symptoms include weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional urethral and anal sphincter activities, and dysfunction of the autonomic nervous system that can lead to episodes of high blood pressure. Symptoms typically develop over the course of hours to a few weeks. Sensory symptoms of TM may include a sensation of pins and needles traveling up from the feet.
Therefore, cancer cells which divide much more rapidly than most other cells in the body will be more severely affected by decitabine just because they replicate more. In cancer cells, and more specifically in haematological malignancies, it seems that DNA hypermethylation is really critical for their development. Methylation of CpG islands upstream of tumor suppressor genes in order to silence them seems to be critical for these type of cancers. Thus at optimal doses, decitabine blocks this type of methylation and has an anti-neoplastic effect. Research
Atherosclerosis
A number of investigators have shown a relationship between atherosclerosis and disturbed blood flow. This upregulates DNA methyltransferase expression, which leads to genome-wide DNA methylation alterations and global gene expression changes. These studies have revealed several mechanosensitive genes, such as HoxA5, Klf3, and Klf4, whose promoters were hypermethylated by disturbed blood flow, but rescued by DNA methyltransferases inhibitors such as 5-aza-2-deoxycytidine. It has been found that use of this DNA methyltranferase inhibitor prevents atherosclerosis lesion formation and reduces the production of inflammatory cytokines by macrophages. References
Further reading
Moon C, Kim SH (June 2009). "Use of epigenetic modification to induce FOXP3 expression in naïve T cells". Transplant. Proc. 41 (5): 1848–1854. doi:10.1016/j.transproceed.2009.02.101. PMID 19545742. External links
"Decitabine". Drug Information Portal. U.S. National Library of Medicine.