Today due to improvements in cancer treatment there is an increasing number of long-term cancer survivors, many of whom suffer from infertility caused by malignancy itself and chemo- or radiotherapy. Also, anticancer therapy may cause myelosuppression. Presently granulocyte colony stimulating factor (G-CSF) is used for prevention and treatment of myelosuppression. Another treatment option used to decrease intoxication and ameliorate side effects of cancer therapy is sorption technology. The aim of our investigation was to study the efficiency of combined use of enterosorption and G-CSF to decrease gonadal toxicity of chemotherapy. Materials and Methods: Melphalan (L-PAM) injected i.v. at a single dose of 4 mg/kg to white inbred rats was used as gonadotoxic and myelosuppressing agent. Carbon enterosorbent C2 was administered by intragastric route as a suspension in saline at a dose of 5 ml per 1 kg of rats’ body weight (or 900 mg/kg of the dry mass of enterosorbent) daily for 3 days before and for 7 days after L-PAM injection. G-CSF was injected once a day for 4 days starting from the next day after L-PAM administration at a dose of 50 µg/kg. Histological preparations of testicular tissues were examined by light microscopy. Results: Our findings have shown that melphalan caused marked damage of testicular tissues and seminiferous, especially spermatogenic epithelium. The most expressed protection of the histological structure of testes was observed when enterosorbent and G-CSF were used in combination. Conclusion: Gonadal toxicity of chemotherapy could be efficiently decreased by the combined use of enterosorption and G-CSF.

Background. Stroke is among the leading causes of death and disability worldwide with rising incidence among young people today. This is the third most common cause of disability-adjusted life-years worldwideObjective. The present study evaluated the cerebroprotective action of coordination compounds of germanium with underlying global cerebral ischemia in rats.Methods. Global cerebral infarction was induced by bilateral common carotid artery occlusion. For primary screening we used numerous bis(citrate) germanates (stannates) compounds, which contained different metals: OL1-8, and VITAGERM-1,2,3 and 4. All germanium complexes used were injected intraperitoneally (1 % aqueous solution at a dose of 50 and 100 mg/kg in 35 min after bilateral common carotid artery occlusion). Piracetam was used as a reference drug. Criteria of cerebroprotection efficacy: survival of rats (%), ET50 (median effective time), observational Irwin’s test.Results. Almost all bis(citrate) germanates (stannates), which contained different metals, possessed anti-ischemic activity of different intensity. The exceptions were cobalt-containing OL-6 and OL-2 compounds. The most significant efficacy of all investigated indices (which exceeded even reference drug) was evidenced for VITAGERM-1 – a coordination compound of germanium, diethylenetriaminepentaacetic acid and lithium. Conclusions. Results of our experiments are the substitution for further more profound pharmacological investigation of VITAGERM-1 for stroke cerebroprotection and its implementation into clinics.

The liver failure means inability to perform its normal synthetic, biotransformation and excretory functions. The disturbance of metabolic processes leads to the development of "metabolic endogenous intoxication" resulting in oxidative stress. Oxidative stress initiates the processes of oxidation of amino acid residues of blood plasma proteins causing the changes in their structure and functions. The effect of administration of highly activated porous carbonic enterosorbents on oxidative stress manifestations and molecular conformation of serum albumin in blood of experimental animals with acute liver failure induced by carbon tetrachloride (CCl 4) needs to be investigated. Two forms of activated carbonic enterosorbents such as AC1 (primary beads with the range of diameters of 125-250 μm) and AC2 (secondary granules prepared from micronized AC1 having the mean particle size of~1 μm) derived from phenol-formaldehyde resin were used in rat model with CCl 4 intoxication. The total level of reactive oxygen species (ROS) in blood plasma, the activity of catalase (CAT) in blood hemolysates; the content of reduced glutathione (GSH) in liver homogenates, and the level of oxidative modification of proteins (OMP) such as aldehyde-dinitrophenylhydrazone (A-DNPH) and ketone-dinitrophenylhydrazone (K-DNPH) derivatives in blood plasma and liver homogenates were determined. In addition, the level of pro/antioxidant ratio in blood hemolysates and the content of lipid peroxidation product-malondialdehyde (MDA), in blood plasma and liver were determined. Melting thermograms of blood plasma proteins (BPP) and molecular conformation changes of serum albumin were analyzed by biophysical methods (differential scanning microcalorimetry and spectrofluorimetry). The extent of CCl 4-induced oxidative damage in blood and liver of experimental animals was shown to be less expressed for AC1 in comparison with AC2 enterosorbent. However, AC2 used in the form of secondary granules positively influenced some biophysical properties of albumin molecule (temperature of melting, shape of melting endotherm and intrinsic fluorescence) after rats exposure to CCl 4. In general, administration of both AC1 and AC2 led to the reduction of oxidative stress manifestations and partial restoration of native molecular conformation of serum albumin. These observations are promising in terms of achieving recovery of detoxification potential of organism after severe liver injury.

Background and Objectives: Side effects of anti-cancer drugs are usually accompanied by oxidative stress, including myelotoxicity. We evaluated the potential of oral highly activated micro-/macroporous carbon adsorbents (bulk density of 0.16 g/cm3, surface area calculation by Brunauer–Emmett–Teller model (SBET) > 2200 m2/g, derived from proprietary phenolic resin beads) to alleviate oxidative stress and myelotoxicity in rats. Materials and Methods: A single injection of cytostatic melphalan (L-PAM) at a dose of 4 mg/kg was used for modelling. Two forms of activated carbon were used: AC1—primary beads with the particle size range of 125–250 µm, and AC2—micronized AC1 with a mean particle size of ~1 µm. We measured haematological parameters white blood cells, red blood cells, platelet count, and haemoglobin level. Oxidative stress intensity was evaluated using the following markers: total levels of reactive oxygen species (ROS) in blood plasma; catalase activity (CAT) and pro-oxidant/antioxidant ratio in blood haemolysate samples; level of reduced glutathione (GSH) in liver tissues; oxidative modification of proteins, OPM (APHD, aldehyde–dinitrophenylhydrazone derivatives and KPHD, ketone dinitrophenylhydrazone derivatives) and malonic dialdehyde (MDA) in blood plasma and liver samples. Results: AC2 administration promoted significant myeloprotective effect: 1.5-fold increase in leukocytes, 2-fold in neutrophils, 1.5-fold in lymphocytes, and 1.23-fold in platelet count compared to the experimental Melphalan Group. At the same time, AC1 administration resulted in a slight increase in haematological parameters. Both ACs positively corrected important, but diverse, components of oxidative stress. They significantly reduced oxidative modification of blood and liver proteins (especially the AC1 form), normalized the level of reduced glutathione, pro-oxidant/antioxidant ratio and other markers. For some markers, such as ROS production in blood plasma, the use of enterosorbents resulted in non-significant a shift towards normal parameters. Conclusions: Oral activated carbon adsorbents reduce oxidative stress intensity and myelotoxicity; they can be promising means to combat the adverse effects of chemotherapy in clinical practice.

Summary. The potential of one of the adsorption methods, enterosorption (ES), using the new generation of carbon adsorbents to correct the negative manifestations of tumor-host interaction in the framework of paraneoplastic syndrome (PNS) as well as systemic toxicity of chemo- and radiation therapy, is discussed. The ES influence on the development of PNS was demonstrated in C57/BL6 mice with transplanted Lewis lung carcinoma. Two-week administration of carbon enterosorbents resulted in a significant suppression of metastasis and correction of tumor-related anemia, activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of its mitotic activity. ES exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, increased resistance of erythrocyte membranes and decreased ligand loading of blood plasma transport proteins. The effect of ES on anticancer activity and toxic reactions of cisplatin (CP) was evaluated in Guerin carcinoma-bearing rats. ES reduced significantly creatinine and other kidney biochemical indexes elevated in the blood plasma of rats after CP treatment. ES attenuated dystrophic changes in the histological structure of internal organs (kidney, liver, spleen), caused by tumor growth and significantly aggravated under the influence of CP. Such changes were specially traced in the kidneys and well reflect the nephroprotective potential of ES. In rats irradiated with X-ray in sublethal dose, highly activated granulated carbonic enterosorbents facilitated the restoration of white blood cells and lymphocyte count. The results obtained confirm the insights of academician R.E. Kavetsky predicting the future of adsorptive detoxification with activated carbons in the treatment of cancer patients.

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Мета роботи – аналіз проблем раціонального застосування антибіотиків та шляхів їх вирішення при викладанні фармакології. Основна частина. Проаналізовано основні проблеми, які перешкоджають ефективній антибіотикотерапії у наш час (прогресуюче зростання резистентності мікроорганізмів, нераціональне, надмірне застосування антибіотиків у клінічній практиці) та підкреслено важливість подачі цього матеріалу студентам для усвідомлення ними належних правил використання антибіотиків.  Висновок. Аналіз причин антибіотикорезистентності, проблем раціонального призначення антибактеріальних препаратів та шляхів їх вирішення при викладанні теми “Фармакологія антибіотиків” є важливою складовою ефективного опанування студентами цього важливого матеріалу з метою використання у майбутній лікарській діяльності.