Revisiting the methylation hypothesis for the psychoses.
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Biomedical subjects
Publications and source records attributed to Jacob Peedicayil.
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Epigenetics, heritable changes in gene expression that do not involve changes in DNA sequence, is known to be involved in disease. Two important epigenetic changes that are known to contribute to disease are abnormal methylation patterns of DNA and modifications of histones in chromatin. This review describes a new development in pharmacology, epigenetic therapy, which attempts to correct these changes. At present two groups of drugs are being developed. One inhibits DNA methyltransferases (DNMTs) resulting in the inhibition of DNA methylation. This group of drugs may prove to be useful in the treatment of cancer where hypermethylation of tumour suppressor genes is known to lead to silencing of these genes. The other group of drugs inhibits histone deacetylases (HDACs) resulting in the accumulation of acetylated histones which are thought to mediate the anticancer effects of these drugs. Both these drug groups have shown promising results in drug trials for the treatment of cancer. Since epigenetic changes are thought to underlie a wide range of diseases, the scope of epigenetic therapy is likely to expand.
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OBJECTIVE: To determine the effect of a nicorandil congener, SG-209 on the myometrium. STUDY DESIGN: Isolated strips of myometrium, from nine women who underwent hysterectomy, were made to contract with 55 mM KCl before and after incubation with three concentrations of SG-209 (1.5, 3.0 and 10 microM). The mean height of contraction and the area under the curve were analysed using a non-parametric test. RESULTS: At a 10 microM concentration, SG-209 significantly decreased the mean area under the curve from 10.8 to 2.5 cm2 (p<0.05). CONCLUSION: SG-209 significantly relaxes the human non-pregnant myometrium. Along with its congener, nicorandil, it may be useful in clinical conditions that require uterine relaxation.
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There is evidence suggesting that the primary (idiopathic) mental disorders are due to epimutations involving genes that determine the structure of the brain. Although in the past it has been suggested that the genes underlying the primary mental disorders may be unidentifiable, recent developments in neuroscience suggest otherwise. This paper outlines various epigenetic strategies that may help identify the genes underlying these disorders.
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