THE REPRODUCTIVE HEALTH OF THE FEMALE RESIDENTS IN THE AREAS OF UKRAINE AFFECTED BY THE RADIOACTIVE CONTAMINATION (2007-2017). / REPRODUKTYVNE ZDOROV'Ia ZhINOK-MEShKANOK RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆ UKRAÏNY (2007­2017 rr.).

OBJECTIVE: analysis of some reproductive health disorders of female residents of radioactively contaminated (con- taminated) and clean territories of Ukraine. MATERIALS AND METHODS: Data on disorders of the menstrual cycle (DMC), cancer of the body of the uterus (BU), inflammatory diseases of the uterus cervix (IDUC), which are taken from the statistical reports of the Ministry of Healthcare of Ukraine, from the State Statistics Service of Ukraine and the Kiev Regional Center for Maternal and Child Health Depending on Residence for the period 2007-2017, depending on the residence in the radioactively contaminated or clean settlement. RESULTS: The prevalence and incidence of DMС increased from 2007 to 2017 from 17.79 ‰ and 10.66 ‰ to 18.50 ‰ and 11.66 ‰, the prevalence and incidence rates of IDUC (from 10.05 ‰ and 7.11 ‰ to 12.50 ‰ and 8.60 ‰), there was a negative tendency of incidence of malignant neoplasms of BU (an increase of 32.2 %) and UC (an increase of 5.1%). The incidence of BU cancer in 2014-2017 compared to Ukraine as a whole (0.14 ‰) in Kyiv region and Zhytomyr region increased (0.17 ‰, p <0.01 and 0.17 ‰, p < 0.01), and in Rivne region it was no diffe- rent from the national one (0.12 ‰). The lowest prevalence and incidence of DMC were found in Rivne region (10.41 ‰ and 6.85 ‰), which is almost twice lower than in Zhytomyr region (24.78 ‰ and 11.16 ‰). In Kyiv region, these figures are also significantly lower than in Ukraine (14.48 ‰ and 10.10 ‰). In the Kyiv region, there was no difference in the frequency of DMC (389.57 ‰, versus 405.99 ‰, p = 0.72), hyperplasia (67.48 ‰ vs. 59.95 ‰, p = 0.80), and BU polyps (46.01 ‰ against (57.22 ‰, p = 0.62) in contaminated and clean territory, with no such difference found for women from 1970-1987. CONCLUSIONS: Against the background of an increased incidence of BU cancer in the contaminated territories of the Zhytomyr region and Kyiv region, the prevalence and incidence of DMC was higher than the national level only in Zhytomyr region, whereas in Kyiv region and Rivne region, on the contrary, the indicators were lower. There is no dif- ference in the frequency of DMC, endometrial hyperplasia, BU polyps, both individually and in combination, among women who lived in the contaminated and clean territory of the Kyiv region.

Antitumor effects and hematotoxicity of C60-Cis-Pt nanocomplex in mice with Lewis lung carcinoma.

BACKGROUND: Cisplatin (Cis-Pt) is a widely used anticancer drug but its therapeutic efficiency is limited by hemato-, cardio-, hepato-, nephro- and neurotoxicity. Complexation of Cis-Pt with C60 fullerene nanoparticle will allow to enhance the antitumor activity of the drug and to reduce its side toxic effects. AIM: To estimate the antitumor effects of С60-Cis-Pt nanocomplex in Lewis lung carcinoma (LLC) and analyze hematological toxicity in tumor-bearing mice. MATERIALS AND METHODS: Complexation of C60 fullerene and Cis-Pt molecule was studied by computer simulation. С60-Cis-Pt nanocomplex was i.p. injected to LLC-bearing mice in a total dose of 7.5 mg/kg (C60:Cis-Pt as 3.75:3.75 mg/kg). The survival of tumor-bearing mice and the relative reduction of tumor weight was recorded. Blood indices were determined using the Particle Counter PCE-210 automatic hematology analyzer. RESULTS: Computer simulation demonstrated the formation of С60-Cis-Pt nanocomplex in physiological medium and its stability due to the hydrophobic interactions. Treatment with C60-Cis-Pt nanocomplex increased survival time of LLC-bearing mice by 32%, normalized hemoglobin content (up to 100 g/l), erythrocyte and platelet count as compared to the untreated LLC-bearing mice. Tumor weight decreased by 35.5%; the mitotic index of tumor cells decreased by 78%, and apoptotic index increased by 75%. The revealed effects of the C60-Cis-Pt nanocomplex were more pronounced than the effects of Cis-Pt or C60 fullerene alone in equivalent dose. CONCLUSION: Treatment with C60-Cis-Pt nanocomplex prolonged the survival of LLC-bearing mice and reduced anemia in LLC-bearing mice.

Effect of С60 fullerenes on the intensity of colon damage and hematological signs of ulcerative colitis in rats.

The application of pristine С60 fullerene aqueous colloid solution (C60FAS; 0.5 mg/kg body weight) for rats experienced acute colitis, either intraperitoneally or intrarectally (1) restores the colonic mucosa healing and epithelial barrier integrity, evidenced by autopsies and histological findings and the normalization of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of hemorrhages, such as signs of anemia and increased platelet count; (3) improves the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and protein carbonyl group levels tended down) and stimulating the antioxidant defense system (glutathione peroxidase activity grew up). In addition, C60FAS intrarectally increases the monocyte count and decreases content of neutrophil granulocytes, i.e. diminishes the rate of the inflammatory process and activates the processes of colon tissues restoring with monocytes involvement. Therefore, intrarectal administration of C60FAS may serve as an efficient tool of ulcerative colitis therapy.

Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo.

The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

[MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug

[MORPHOFUNCTIONAL PARAMETERS OF BLOOD CELLS OF THE RAT WITH 1,2-DIMETHYLHYDRAZINE-INDUCED COLON CARCINOGENESIS].

Morphofunctional parameters of blood cells of the rats with dimethylhydrazine induced colon carcinogenesis have been investigated. The reduction of Mean corpuscular hemoglobin (MCH) and Mean corpuscular hemoglobin concentration (MCHC) whereas increasing of reticulocytes number and indirect bilirubin after 20 weeks of experiment of dimethylhydrazine (DMH)-induced colon carcinogenesis indicate the hemolysis of red blood cells due to the DMH influence during tumors development. The moderate increasing of monocytes and platelets number, as well as increment of eosinophilic granulocytes number have been observed. 26 weeks of experiment (after 6 weeks discontinuation of DMH) leads to reduction of hemoglobin and erythrocytes number, a moderate increase of monocytes number and increment of platelets number in rats blood. The anemia with thrombocytosis accompany cancer in humans and the model of DMH-induced colon cancer is appropriate not only for studies of carcinogenesis and searching of new antineoplastic drugs, but also for the development of the correctional approaches of cancer-associated changes in the hematopoietic system.

[NET WATER TRANSPORT VIA RAT COLON EPITELIUM UNDER THE EXPERIMENTAL DYSBIOSIS].

The aim of the present study was to investigate the effect of cephalosporin antibiotic ceftriaxone (50 mg/kg, i/m) and mac- rolide antibiotic azithromycin (15 mg/kg, per.os.) on net water transport across rat colonic epithelium. Study was done on male Wistar rats (180-250 g). Azithromycin or ceftriaxone was injected daily for 5 days. Net water transport was evaluated on the 6th day by isolated colonic loop perfusion technique in vivo on anaesthetized rats. Treatment with azithromycin increased 2,4-fold the absorption of water, while ceftriaxone caused decrease 1,9-fold water absorption. The antibiotics treatment within five days didn't change the composition of the fecal and colonic parietal microbiota. Azithromycin-induced increase in water absorption was associated with upregulation of AQP 8 water channel expression (P < 0.05) in colonic mucosa. Ceftriaxone treatment didn't change protein level of AQP8 but induced pro-inflammatory changes in colonic mucosa structure and mast cells degranulation. We showed for the first time the opposite effects ofmacrolide and cephalosporin antibiotics on net water transport across rat colonic epithelium.

[Hematological effects of the protein kinase inhibitor maleimide derivative in dimethylhydrazin E-induced colorectal carcinogenesis of rats].

The effect of the protein kinase inhibitor maleimide derivative (MI-, 1, 1-(4-Cl-benzyl)-3-CI-4-(CF3-phenylamino)- 1H-pyrrole-2,5-dione) on blood cells of rats with 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis has been studied. Administration of MI-I1 at 2.7 mg/kg for 20 weeks on DMH-induced carcinogenesis prevents anemia, which is a consequence of cancer and complicates it. This is confirmed by a reduction in the numberofreticulocytes (0,19(0,15;0,21)x 10(12)/1)and restoration of mean corpuscular hemoglobin (18,02 (17,44;19,03) pg) and mean corpuscular hemoglobin concentration (309,42 (292,38;318,27) g/L) to a control value (0,17 (0,15;0,19), 18,31 (17,95;18,45), 310,78 (306,25;316,18), respectively) in contrast to the group DMH (0,28 (0,24;0,39); 17,50 (17,00;17,96); 288,10 (284,71;303,73), respectively). MI-I normalizes the number of monocytes (1,40 (0,95;2,50)x 10(9)/L) and platelets (646,32 (575,23;700,50)xl10(9)/L) in the blood after 26 weeks ofexperiment; in the DMH group, the values are significantly higher (1,97 (1,52;2,58), 783,90 (687,64;922,27), respectively) as compared to control group (1,23 (0,94; 1,68), 629,34 (590,19;711,48), respectively). MI- 1 reduces the involvement of these cells in the tumors progression and metastasis. Reduction of the monocytosis and thrombocytosis may be mediated by: 1) a decrease in the number and size of tumors and, consequently, the influence of their cytokines on hematopoietic tissue; 2) suppression of proliferation and differentiation of hematopoietic progenitor cells through inhibiting of receptor protein kinases of vascular endothelial and epidermal growth factors and non-receptor PDKI-, Src- and Syk- kinases, that are involved in hematopoiesis and carcinogenesis.

[The possibilities of congenital pathology primary prophylaxis as responsibility of general practitioner in Ukraine].

UNLABELLED: The aim was to study some tendencies of congenital pathology primary prophylaxis in context of Governmental measures and general practitioner's activity. MATERIALS AND METHODS: The information basis of investigation was made up from foreign and home publications, lawmaking documents and data of questioners. Questioners were filled in by doctors who obtained general practitioner qualification (152 persons). The questioner contained information about sex, age, marital status of future general practitioners. It also contained questions about progress in studies at Medical University, healthy way of life maintenance during pregnancy, understanding of possibility to prevent child birth with congenital malformation, ways of congenital malformations prophylaxis in general practitioner's activity. RESULTS: System approaches to congenital pathology burden reduce started forming. State possibilities are not applied effectively in congenital pathology primary prophylaxis. Doctors who obtain general practitioner qualification understand the importance of healthy way of life and medical and genetic consultation for birth child with congenital malformations preventing. Future general practitioners consider that it is possible to carry out complex of steps for decreasing congenital pathology burden. SUMMARY: It is impossible to carry out special congenital malformations prophylaxis programs because of economic situation in Ukraine. At the same time some results could be achieved due to professional activity of general practitioners and carrying out specific preventive measures on the way to decrease of congenital malformations burden.

[Effect of dihydropyrrol and maleimide derivatives on the state of the liver and colon in normal rats and those with colorectal carcinogenesis induced by dimethylhydrazine].

No liver and colon alterations in rats, caused by cytostatic compounds 5-amino-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one (D1) and 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2,5-dione (MI-1) when administered over a long time were found, as evidenced by the histopathological data and the data of activity of transaminases, alkaline phosphatase and lactate dehydrogenase in the blood serum. D1 and MI-1 in vivo decrease the total area of DMH-induced colon tumors in rats by 46-60%. Furthermore, D1 and MI-1 partially protect the liver and colon mucosa from toxic effects caused by 1,2-dimethylhydrazine (DMH) reducing DNA oxidative modifications, as evidenced by urine 8-hydroxydeoxyguanosine level. The effects of both compounds are similar, but MI-1 is less toxic for the liver and colon of intact animals possessing more pronounced antitumor activity and protective properties in the setting of chemically induced carcinogenesis.