Pyridine Derivative of Succinic Acid Hydroxylamide Enhances the Cytotoxic Effect of Cisplatin and Actinomycin D.

We studied the possibility of inhibition of histone deacetylases (HDAC) in the nuclear extract of HeLa cells by N1-hydroxy-N4-(pyridin-4-yl)succinamide (compound 1). Compound 1 inhibits HDAC and showed low toxicity for A-172, HepG2, HeLa, MCF-7, and Vero cells. HeLa cells were most sensitive to the compound. Increasing the interval between administration of compound 1 and the chemotherapeutic agent to 8 h led to an increase in the cytotoxic effect of cisplatin (actinomycin D) on HeLa cells. The combination of compound 1 with cisplatin (actinomycin D) reduced the cytotoxic effect of these drugs for non-tumor Vero cells.

Nanoparticles of water-soluble dyads based on amino acid fullerene C60 derivatives and pyropheophorbide: Synthesis, photophysical properties, and photodynamic activity.

Synthesis, spectral properties, and photodynamic activity of water-soluble amino acid fullerene C60 derivatives (AFD) and four original AFD-PPa dyads, obtained by covalent addition of dye pyropheophorbide (PPa) to AFD, were studied. In aqueous solution, these AFD-PPa dyads form nanoassociates as a result of self-assembly. In this case, a significant change in the absorption spectra and strong quenching of the dye fluorescence in the structure of the dyads were observed. A comparison of superoxide or singlet oxygen generation efficiency of the studied compounds in an aqueous solution showed the photodynamic mechanism switching from type II (singlet oxygen generation of the native dye) to I type (superoxide generation of dyads). All dyads have pronounced phototoxicity on cells Hela with IC50 9.2 µM, 9.2 µM, 12.2 µM for dyads Val-C60-PPa, Ala-C60-PPa and Pro-C60-PPa, respectively. Such facilitation of type I photodynamic mechanism could be perspective against hypoxic tumors.

[Epidemiological rationale for community-based programs of caries prevention of permanent teeth for children of Samara city]. / Épidemiologicheskoe obosnovanie kommunal'nykh programm profilaktiki kariesa postoiannykh zubov dlia detei Samary.

INTRODUCTION: The global objectives of WHO in the field of oral health by 2020 include the average intensity of caries among 12-year-old children no more than 1.5 by the DMFT index. In Samara the value of the DMFT among the adolescents at age 12 is 3.5. AIM: To identify the appropriate timing for a launching of community-based schemes of dental caries prevention of permanent teeth for children of Samara. MATERIAL AND METHODS: In a cross-sectoral multisample research from March to May 2017, the time of eruption and intensity of caries of the first permanent molars among children in Samara were studied. A total of 405 children aged 5 to 8, attending preschool and school educational institutions were examined. The quantity and the stage of eruption of the first permanent molars were assessed; the initial and manifest forms of caries were considered during the calculation of indexes of caries intensity of teeth and surfaces. RESULTS: One to four first permanent molars were erupted among 26.3% of children aged 5, at an average 0.6±0.14 per one surveyed, the prevalence of caries of the first permanent molars was equal to 1.3%, including 1.3% of the initial carious defeats. In 6-year-old children - 65% had the first permanent molars, at an average of 2.38±0.199, and the prevalence of caries in these teeth was 29.63%, including initial forms of caries 27.16%. The results among 7-year-old children - 87.18% and 3.12±0.156, 60.3% and 51.28%, respectively. In 8-year-old children these figures were equal: 97.26%, 3.79±0.091, 68.49% and 60.27%, respectively. The rate of eruption of the first permanent molars and the prevalence of their carious lesions among girls was significantly higher than among boys. CONCLUSION: The optimal age of children of Samara for inclusion in the regional programs of dental caries prevention is the age of 4 years - the age of the beginning of the first permanent molar eruption.

Comparison of the Effect of Platinum (IV) Complexes on Spheroids and Monolayer Culture of HeLa Cells.

We performed a comparative study of the cytotoxicity of cisplatin, JM216 complex, and aminonitroxyl platinum(IV) complexes for HeLa cells grown in monolayer and 3D culture. The growth dynamics of spheroids was studied and optimal conditions for evaluation of cytotoxicity were determined. Spheroids were less sensitive to the test compounds than cells in a monolayer. The resistance index (RI) of spheroids was determined as the ratio of IC50 for spheroids to IC50 for monolayer culture. Resistance index was 5.0±1.5 for cisplatin and ranged from 1.8 to 2.3 for platinum(IV) complexes. The observed differences are related to different physicochemical properties of the complexes and different mechanisms of their penetration into cells.

Effect of Cytotoxic Compounds on Activity of Antioxidant Enzyme System in MCF-7 and H1299 Cells.

We studied the function of the antioxidant system in tumor cell lines MCF-7 and H1299 that differ by the state of tumor suppressor gene p53. Exposure to different classes of cytotoxic compounds induced several types of antioxidant system responses that depend on the type of cell line. The effects of platinum(II) and platinum(IV) complexes on activity of antioxidant enzymes vary, which can be explained by differences in their accumulation and biotransformation in tumor cells. Triazole and oxazolidinone derivatives had little effect on activity of superoxide dismutase and catalase in H1299 cells, but increased superoxide dismutase activity in MCF-7 cells.

[Peculiarities of epilepsy in women with menstrual dysfunction].

An aim of the study was to optimize the diagnosis and treatment of epilepsy in women of reproductive age with concomitant disturbances of menstrual cycle. One hundred and thirty-two women, aged from 18 to 35 years, were studied. Menstrual dysfunction was found in 47,7% (n = 63): oligomenorrhea--in 68,3% (n = 43), amenorrhea--in 9,5% (n = 6) and dysfunctional metrorrhagia--in 22,2% (n = 14). Based on the character of hormone and ovarian dysfunction, the following syndromes were singled out: polycystic ovaries--54% (n = 34), isolated hypoprogesteronemia--23,8% (n = 15), hypercorticism--14,3% (n = 9), hypogonadotropic hypogonadism--7,9% (n = 5). Different hormonally-active drugs that allowed to normalize the menstrual cycle were used, along with basic antiepileptic drugs, to treat these hormonal dysfunctions and improve the course of epilepsy.

[Epilepsy in adults: a costs-of-illness study].

An aim of the study was to assess clinical-economic effectiveness of therapy in the stages of examination of an epileptic patient by a local neurologist and then by an epileptologist after therapy optimization. Three hundreds and ten patients with different forms of epilepsy and types of epileptic seizures were treated. Costs-of-illness and medical services were assessed using common parameters on the basis of current prices in the health-care system. Special attention was drawn to expenses related to purchasing of antiepileptic drugs (traditional and new ones). The expenses for treatment were compared to treatment effectiveness. It is concluded that mean costs of treatment of epilepsy, including new brands of antiepileptic drugs with high prices, have substantial medical-social benefits that compensate expenses for their purchasing at the expense of other direct and indirect costs.