Applying Patient-Specific Induced Pluripotent Stem Cells to Create a Model of Hypertrophic Cardiomyopathy.

Generation of patient-specific induced pluripotent stem cells (iPSCs) and their subsequent differentiation into cardiomyocytes opened new opportunities for studying pathogenesis of inherited cardiovascular diseases. One of these diseases is hypertrophic cardiomyopathy (HCM) for which no efficient therapy methods have been developed so far. In this study, the approach based on patient-specific iPSCs was applied to create a model of the disease. Genetic analysis of a hypertrophic cardiomyopathy patient revealed R326Q mutation in the MYBPC3 gene. iPSCs of the patient were generated and characterized. The cells were differentiated into cardiomyocytes together with the control iPSCs from a healthy donor. The patient's iPSC-derived cardiomyocytes exhibited early HCM features, such as abnormal calcium handling and increased intracellular calcium concentration. Therefore, cardiomyocytes obtained by directed differentiation of iPSCs from the HCM patient can be used as a model system to study HCM pathogenesis.

Generation of two clonal iPSC lines, ICGi019-A and ICGi019-B, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.M659I mutation in MYH7.

Hypertrophic cardiomyopathy (HCM) is one of the most frequent cardiovascular diseases but no methods to prevent its progression have been developed. Cardiomyocytes derived from patient-specific induced pluripotent stem cells can become a platform to study pathogenesis of the disease and to search for more effective therapy methods. We generated two iPSC lines from peripheral blood mononuclear cells of an HCM patient with heterozygous p.M659I mutation in MYH7 using episomal vectors. The iPSC lines expressed pluripotency markers, demonstrated ability to spontaneously differentiate into derivatives of three germ layers, and retained the mutation.

Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.

Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers. These cell lines may be useful for studying molecular mechanisms of PD and for drug screening.

[The prevention of the side effects of cytostatics by administering them at various times of day]. / Profilaktika pobochnogo deistviia tsitostatikov putem ikh vvedeniia v razlichnoe vremia sutok.

Rats bearing Pliss' lymphosarcoma revealed diurnal variations of body temperature. Cyclophosphamide and methotrexate were significantly less toxic when injected at peak temperatures than at minimal ones.

[Circadian rhythm of adenosine triphosphatase activity and 32P content in Pliss lymphosarcoma]. / Sutochnyi ritm aktivnosti adenozintrifosfataz i soderzhaniia 32P v limfosarkome Plissa.

Within a daily period maximal activity of ATPases and content of 32P in Pliss lymphosarcoma tissue was found in the samples taken at 15 or 21 p.m. and 3 a.m. The radioactivity in the tumor was minimal between 9 and 12 a.m. and 18 or 24 p.m. The alterations in Mg2+-ATPase activity in their magnitude and circadian rhythm coincided completely with the daily variations in content of radiophosphorus. Activities of Na+, K+- and HCO(3-)-ATPases exhibited maximal values at 15 p.m. and, especially between 3 and 6 a.m., i.e. these alterations were of two-peak shape without the peak at 21 p.m.

[Sulfazin in the thermoradiotherapy of experimental tumors]. / Sul'fazin v termoradioterapii éksperimental'nykh opukholei.

A possibility of radiosensitization of Pliss' lymphosarcoma and tumor RS-1 by using general hyperthermia with sulfazin was studied. Subcutaneous transfusion of sulfazin to rats caused a rise of the body temperature by 2-2.5 degrees C on the 2nd day after injection with the upkeep of hyperthermia for 3 days. A combined effect of sulfazin and irradiation enhanced the retardation of growth rate of tumors and increased their regression. The lifetime of animals increased significantly. A more noticeable postradiation suppression of mitotic activity was observed.

[Potentiation of the radiosensitizing effect of metronidazole using whole-body drug-induced hyperthermia]. / Usilenie radiosensibiliziruiushchego éffekta metronidazola pri pomoshchi obshchei medikamentoznom gipertermii.

The total drug hyperthermia in the presence of metronidazole administration improves radiotherapeutic results in Pliss lymphosarcoma: tumor growth inhibition increases by 12.7-18.5%, tumor regression by 30.6-38.9%. A dose of 100 mg/kg of metronidazole combined with irradiation in the presence of moderate hyperthermia produces even a more noticeable radiosensitizing effect than a dose of 700 mg/kg without hyperthermia. A possibility of quite a high level of tumor radiosensitization with lower doses of metronidazole without toxic manifestations of the body was shown.