Молекулярная и генетическая медицина

This paper describes a methodology to develop a new method for qualitative and quantitative determination of glibenclamide (GLB) in three brands of GLB tablets. We validated the developed method for linearity, accuracy, precision, limit of detection (LOD) and limit of quantification (LOQ) according to the guidelines of the International Conference on Harmonization. Finally, we estimated the qualitative and quantitative amount of GLB in three brands of GLB tablets using validated method. A non significant difference was observed in the dissolution profiles of GLB in these tablets. Validation of developed method showed that a linear relationship (r²0.999) was observed at maximum absorbance (λ_max) at 229.5 nm with concentration range of 3-15 μg/ml GLB. Accuracy of developed method was found to be within the limit of 95-105%. The percent relative standard deviation (%RSD) and percent relative error (%RE) for precision was found to be <3%. In three brands of GLB tablets, values of LOD and LOQ were 10 ng/ml and 35 ng/ml respectively. We also found that the amount of GLB in each tablet corresponded to the requirements of 95-105% of the label claimed in tablet. From the results of validation of developed method, it concluded that developed method showed satisfactory linearity, precision and accuracy for analysis of active ingredients of commercially available pharmaceutical products.

The relationship between supplemental thiamine and Wilson’s disease has been the focus of recent investigation;and supplemental thiamine has been reported to modulate Wilson’s disease. Genetic studies have helped identify a number of factors that link thiamine to Wilson’s disease, including transcription factor p53, Bcl-2, caspase-2, heme oxygenase-1, and apolipo protein E. Thiamine has also been implicated in Wilson’s disease through its effects on serotonin, reactive oxygen species, and nitric oxide synthase. Therefore, further investigations of thiamine in Wilson’s disease are needed to clarify this relationship.

Primary Ovarian Failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles. It causes infertility in ~1% of women <40 years of age and it has important health consequences for affected patients. POF is a heterogeneous disease, which can develop as a result of a broad variety of pathogenic mechanisms including genetic, autoimmune and iatrogenic causes. However, the mechanisms that cause ovarian dysfunction are poorly understood. Focus on genetic component of the disease has revealed the existence of several causal genetic defects, thus indicating that in addition to some monogenic forms, POF may frequently be a multifactorial disease involving several gene abnormalities and chromosome aberrations. Moreover, most recent studies have highlighted that epigenetic mechanisms may give an additional contribution to POF pathogenesis. This review gives a picture of the state of the art of the complex genetic and epigenetic defects associated with POF, being it clear that a deep comprehension of the molecular etiology of POF may in future early identify those women with higher risk of POF.

The androgen receptor (AR) has been identified for decades and mediates essential steroid functions. Like most of biological molecules, AR functional activities are modulated by post-translational modifications. This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on prolinedirected serine/threonine phosphorylation that occurs predominantly on the receptor. The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

RGPR-p117 was initially discovered as novel protein which binds to the nuclear factor I (NF1)-like motif TTGGC(N)₆CC in the regucalcin gene promoter region (RGPR). RGPR-p117 is localized to the nucleus with stimulation of protein kinase C-related signaling process. Overexpression of RGPR-p117 has been shown to enhance regucalcin mRNA expression in the cloned normal rat kidney proximal tubular epithelial NRK52E cells in vitro. This process is mediated through phosphorylated RGPR-p117. Overexpression of RGPR-p117 was found to suppress apoptotic cell death induced after stimulation with various signaling factors in NRK52E cells, while it did not have an effect on cell proliferation. Moreover, RGPR-p117 was found to localize in the plasma membranes, mitochondria and microsomes, suggesting an involvement in the regulation of function of these organelles. After that, RGPR-p117 was renamed as Sec16B that is involved in the endoplasmic reticulum export. However, this is not suitable name with many findings of the role of RGPR-p117 in cell regulation. RGPR-p117 may play an essential role as transcription factor, and the elucidation of other roles in cell regulation will be expected.