The regulation of genetic expression is tightly controlled and well balanced in the organism by different epigenetic mechanisms such as DNA methylation and histone modifications. DNA methylation occurring after embryogenesis is seen mainly as an irreversible event. Even small changes in genomic DNA methylation might be of biological relevance, and several factors influencing DNA methylation have been identified so far, one being homocysteine. In this study, genomic DNA methylation was analyzed and homocysteine plasma levels were measured over a 24 h period in 30 healthy students (15 males and 15 females) exposed to a standard 24 h regime of daytime activity alternating with nighttime sleep. Plasma homocysteine concentrations were measured using HPLC detection. DNA was extracted from whole EDTA blood, and genomic DNA methylation was assessed by fluorescently labeled cytosine extension assay. Both homocysteine and DNA methylation showed 24 h variation. Homocysteine showed a significant daily rhythm with an evening peak and nocturnal nadir in all subjects (p<0.001). Males showed higher overall homocysteine levels compared to females (p=0.002). Genomic DNA methylation showed a significant rhythm with increased levels at night (p=0.021), which was inverse to plasma homocysteine levels.
This review deals with the treatment of inherited classical galactosemia by a lactose-free diet. Although, with dietary treatment, there is a remarkable improvement in the acute phase of the disease, the long-term outcome has been disappointing for most patients, especially regarding the central nervous system and ovarian dysfunction in females. There is a need for new approaches to treatment, in combination with diet therapy, that could improve the outcome of patients with galactosemia.
The numbers of mitoses in the epithelial and stromal tissues of mouse uteri were recorded after treatment with various doses of progesterone (P), levonorgestrel (LN), and STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9(10)-diene-3-one). All three progestins induced mitotic activity in the stromal tissue of the endometrium in which P and LN were much more active than STS 557. While the cell divisions in the luminal and glandular epithelium induced by P were only rare, LN and STS 557 enhanced the mitosis rates in these tissues significantly at a daily dose of 1.0 mg/animal on 5 consecutive days. The results are discussed with special regard to the post-coital antifertility effect of STS 557.
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