[Aerobic exercise and fatigue indices in rheumatoid arthritis patients in the health resort care setting]. / Aerobnye uprazhneniya i pokazateli ustalosti u bol'nykh revmatoidnym artritom v usloviyakh sanatorno-kurortnogo lecheniya.

Fatigue is one of the most common symptoms of rheumatoid arthritis (RA). There is strong evidence that physical activity is an effective way to reduce fatigue. OBJECTIVE: To evaluate the effectiveness of aerobic exercise (walking) to reduce fatigue in RA patients in the health resort setting. MATERIAL AND METHODS: The study involved 102 female patients with RA (age 54.38±11.3 years, body mass index 20-29 kg/m2, DAS28-ESR ≤3.2, with severe fatigue of VAS ≥50) who received 21 days of health resort treatment. The health-improving and therapeutic complex includes dosed physical activity, aerobic exercises (walking). Visual analog scale (VAS0-100) and Bristol Rheumatoid Arthritis Fatigue Scale-Numerical Rating Scale (BRAF-NRS V2) were used to assess fatigue, and the 50-meter walking test was used to evaluate the functional status of patients. RESULTS: A correlation between walking duration and the number of steps at a distance of 50 m (p<0.001) as well as between these indices and fatigue (p<0.001) was shown. A positive effect of a standard three-week medical rehabilitation program for patients with RA on fatigue NRS severity (p=0.003) and NRS effect (p=0.037), as well as on patients' functional status (reduced time spent on the 50-meter test, p=0.01) was demonstrated. When comparing groups of RA patients with low (group 1, <5000-6000 steps per day) and optimal (group 2, ≥7000-8000 steps per day) aerobic exercise, positive results were noted in the short term (at 3 weeks) (p<0.001). CONCLUSION: Aerobic exercise is a promising intervention for treating fatigue in rheumatoid arthritis patients. Medical rehabilitation in a resort setting is the best starting point to encourage performing regular physical activity, as well as the best way to develop exercise programs tailored to rheumatoid arthritis patients.

Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract.

[Experimental technology of chemoperfusion treatment for abdominal carcinomatosis in ovarian cancer].

An experimental technology of normothermic intraperitoneal chemoperfusion and hyperthermic intraperitoneal chemoperfusion with cisplatin and dioxadet has been elaborated to treat abdominal carcinomatosis in ovarian cancer. Antitumor effects of the treatment were evaluated for the duration of animal life. Normothermic intraperitoneal chemoperfusion and hyperthermic intraperitoneal chemoperfusion with cisplatin and dioxadet in comparison with the standard intraperitoneal administration significantly increased the median life expectancy by 75-92%. Hyperthermic intraperitoneal chemoperfusion with dioxadet demonstrated potentiation of antitumor effect of hyperthermia and dioxadet. Experimental technology is recommended for testing new drugs and methods of chemoperfusion for malignant tumors affecting the peritoneum.

[Antitumor effect of dioxadet in intraperitoneal chemoperfusion treatment for advanced ovarian cancer in experimental setting].

The study of antitumor efficacy of dioxadet in chemoperfusion treatment of ascitic ovarian cancer was carried out in 125 Wistar female rats. Ovarian cancer was inoculated intraperitoneally at a number 1x10(7) tumor cells per rat. Intraperitoneal administration of dioxadet as well as chemoperfusion was performed once in 48 hours after the ovarian cancer inoculation. Dioxadet was used at maximal tolerated doses which were 1.5 mg/kg for intraperitoneal administration, 30 mg/kg for normothermic intraperitoneal chemoperfusion (IPEC), and 15 mg/kg for hyperthermic intraperitoneal chemoperfusion (HIPEC). Antitumor effects of dioxadet were estimated in increase of median survival. In the control group, where animals didn't receive any treatment, the median survival was 9 days. Increase of the median survival after intraperitoneal administration of dioxadet, IPEC and HIPEC with dioxadet was 211% (p=0,001), 244% (p=0,001) and 444% (p=0,001), respectively, compared to the control group. Hence, intraperitoneal chemoperfusion with dioxadet (normo- or hyperthermic) is more effective compared to standard intraperitoneal administration of the drug. At HIPEC with dioxadet potentiating antitumor action of hyperthermia and dioxadet on the ovarian cancer growth was achieved.

[Comparative effects of difluoromethylornithine and tincture of Siberian ginseng root on radiation carcinogenesis and life span in rats].

Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been studied. The results of the study demonstrate that DFMO as well as TSGR significantly improved survival and decreased incidence and multiplicity of malignant and benign tumors in rats subjected to ionizing radiation. Beneficial effect on the rat survival rate and anticarcinogenic action of DFMO were more expressed compared with TSGR.

[Anticarcinogenic effect of potassium salts of glucaric and glucuronic acid in induced models of cervical and esophageal tumors].

This study compares the anti-carcinogenic activity of calcium glucarate, potassium glucarate, and potassium glucuronate in cervix and esophagus induced cancer murine models. The cervical cancer induction was performed by tampons moistened with 0.1% solution of 7,12-dimethylbenz(a) anthracene (DMBA) applied intravaginally twice a week for 6 weeks in mice. Esophageal cancer was induced by oral administration of 10 mg of N-methyl-N-benzylnitrosoamine (MBNA) with drinking water for 1 month in rats. The 2 g per kilo of studied substances was administered orally with food immediately after the exposure to cancerogens for the period of 11 months. Compared to the control group the calcium glucarate, potassium glucarate and potassium glucuronate introduction reduced the incidence of cervical cancers by 20.4%, 32.1%, and 30.0% (p<0.05), accordingly; calcium glucarate introduction decreased only the medium number of the esophagus tumors by 44.3% (p<0.05); potassium glucarate and potassium glucuronate reduced the incidence of esophagus tumors by 35.1% and 61.3% (p<0.05) and their number by 32% and 58.5% (p<0.05), accordingly. Compared with calcium glucarate, potassium salts of glucaric and glucuronic acids inhibit cervical and esophageal carcinogenesis more effectively.

[Inhibitory effect of bioginseng on radiation-induced carcinogenesis in rats].

Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats.

[Anticarcinogenic action of dietary supplement pheocarpin and its active component].

Anticarcinogenic action of dietary supplement Pheocarpin and its active component Natural Coniferous Complex (NCC), in particular, has been studied. Pheocarpin and NCC efficiently inhibited tumorigenesis in the mammary gland, large bowel, skin, cervix uteri and lungs. Pheocarpin offers considerable advantage as a means of reducing the risk of malignant disease.

[Investigation of the drug "Mamoclam" for the treatment of patients with fibroadenomatosis of the breast].

The clinical trial of a new drug "mamoclam" was carried out in patients with benign breast disease. The drug contains omega-3 polyunsaturated fatty acids, iodine and chlorophyll derivatives and is produced from the brown sea alga laminaria. The study involved 33 patients (mean age 42.5 +/- 1.1 yrs). Two tablets were administered thrice a day for three months. Examination included clinical evaluation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. Therapeutic response presented as reduced mastalgia, premenopausal syndrome, dysmenorrhea and algomenorrhea, breast cyst regression as well as attenuated pain associated with benign breast disease and palpation. Positive response was reported in 94%. The drug should be recommended for benign breast disease treatment.

[Effect of glucose on fetal weight and the transplacental blastomogenic effect of N-nitrosomethylurea in rats]. / Vliianie gliukozy na massu plodov i transplatsentarnyi blastomogennyi éffekt N-nitrozometilmocheviny u krys.

The N-nitrosomethylurea (NMU)-induced transplacental blastomogenesis in rats was studied under the effect of pre- and postnatal glucose administration. On the 21st day of pregnancy NMU (20 mg/kg) was intraperitoneally administered to rats. From the 7th day of pregnancy experimental rats were treated with 10% glucose solution instead of drinking water, and during 1.5 months after delivery they and their progeny were given 5% glucose solution. The foetal weight in glucose-treated pregnant rate increased. A significant increase of tumour frequency was detected in the progeny of these rats. In male progeny tumours of the nervous system and kidneys typical of NMU effect prevailed and in females--tumours of other organs and tissues, particularly of the mammary gland, pituitary and hemopoietic system. Possible mechanisms of the modifying effect of glucose on the transplacental blastomogenic action of NMU are discussed.

[Effect of the postnatal induction of persistent estrus on the realization of the transplacental action of DMBA in 1st- and 2d-generation rats]. / Vliianie postnatal'noi induktsii postoiannogo éstrusa na realizatsiiu transplatsentarnogo deistviia DMBA u krys pervogo i vtorogo pokolenii.

In rats of the first generation subjected to transplacental DMBA action with subsequent (at the age of 3 months) induction of persistent estrus, the incidence of tumours significantly increased, particularly, those of the nervous system and the mammary gland. Rats of the second generation with induced persistent estrus and not exposed to DMBA developed neoplasms of the nervous system and kidneys which were not observed in the intact control animals. This fact suggests persistence of DMBA transplacental carcinogenic effect in a series of generations.

[Effect of disordered thyroid function on the realization of the transplacental carcinogenic action of N-nitrosomethylurea in 1st- and 2d-generation rats]. / Vliianie narusheniia funktsii shchitovidnoi zhelezy na realizatsiiu transplatsentarnogo kantserogennogo deistviia N-nitrozometilmocheviny u krys pervogo i vtorogo pokolenii.

The F1 rats subjected to the influence of N-nitrosomethylurea (NMU) in dose of 20 mg/kg on the 21 day gestation as a result of postnatal disturbances of the thyroid function induced by long administration of thyroxin (3 mg/100 g, daily), methylthiouracil (MTU; 0.1% solution in tap water) or thyroidectomy have shown a decreased incidence of the nervous system tumours, but not of the kidney tumours, i. e. sites typical of NMU transplacental carcinogenesis. At the same time the NMU transplacental effect increased thyroid carcinogenesis, induced by the MTU postnatal application, which manifested in the increased incidence of malignant tumours of this site. The carcinogenic effect was observed in F2 rats, while some of them developed tumours of the nervous system (14.9%) and kidney (8.5%) but with lower incidence than in F1 (35.4; 14.1%, respectively). The same modifying factors (thyroxin, thyroidectomy, MTU) employed under the same conditions produca similar effect on carcinogenesis in F2 animals.

[Imprinting effect of aroclor 1254 in the metabolic activation of benz[a]pyrene by rat liver tissue]. / Imprintingovyi éffekt aroklora 1254 pri metabolicheskoi aktivatsii benz[a]pirena tkan'iu pecheni krys.

A well-known inductor of a system of multifunctional monooxygenases, the arochlor 1254, being applied to one-day rats produced an imprinting effect which was expressed in a strong and long-term increase in the metabolic activation of benzo(a)pyrene by the liver S9-fraction in the Salmonella/microsome test, as well as in the arylhydrocarbonhydroxylase activity. The imprinting was not revealed when the inductor was applied on the 9th day as well as it was not revealed for 2-acetylaminofluorene in the liver, or benzo(a)pyrene and 2-acetylaminofluorene in the kidneys, independently of the period of application.

[Influence of the polypeptide preparations cortexin and encephalin on the transplacental carcinogenic effect of N-nitroso-N-ethylurea in rats]. / Vliianie polipeptidnykh preparatov korteksina i éntsefalina na transplatsentarnyi kantserogennyi éffekt N-nitrozo-N-étilmocheviny u krys.

The polypeptide preparations cortexin and encephalin from grey and white substances of the cattle brain injected in the postnatal period are studied for their effect on the development of the nervous system and kidney tumours in rats induced transplacentally by N-nitroso-N-ethylurea. The two preparations decreased both the incidence and multiplicity of the brain tumours. It is supposed that the anticarcinogenic effect of these preparations is due to their normalizing action on the differentiation and proliferation of the brain glia cells.

[Effect of ethanol on N-nitrososarcosine ethyl ester-induced carcinogenesis in the esophageal and forestomach mucosa of mongrel rats]. / Vliianie étanola na kantserogenez, indutsirovannyi étilovym éfirom N-nitrozosarkozina v slizistoi obolochke pishchevoda i predzheludka nelineinykh krys.

Administration of N-nitrososarcosine ethyl ether (50 mg/kg, per os, every day during 4 months) to rats induced after 8 months multiple tumours (most often papillomas) of oesophagus and forestomach. Total incidence of tumour-bearing animals was 42.4% in oesophagus and 21.2% in forestomach, distribution of tumours being 85.6 and 14.4%, respectively. The combined administration of carcinogen with 40% water solution of ethanol (0.5 ml, per os, every day during 8 months) did not change general incidence and multiplicity of all tumours, but decreased the relative incidence of oesophagus tumours and increased that of forestomach tumours. Possible mechanisms of organotropism shifts are discussed.

[Effect of polypeptide factors of the thymus, pineal gland, bone marrow and anterior hypothalamus on the realization of transplacental carcinogenesis]. / Vliianie polipeptidnykh faktorov timusa, épifiza, kostnogo mozga i perednego gipotalamusa na realizatsiiu transplatsentarnogo kantserogeneza.

The postnatal action of low-molecular polypeptide factors of thymus (FT), pineal gland (FP), bone marrow (FRM) and anterior hypothalamus (FAH) on transplacental carcinogenic effect of N-nitroso-N-ethylurea in rats was studied. Both FT and FP administrations decreased incidence and multiplicity of tumours and prolonged their mean latent periods. These drugs inhibited mainly the development of tumours of the spinal cord, kidneys and peripheral nervous system but not those of the brain. Both FBM and FAH had no significant influence on transplacental carcinogenesis. FT and FP anticarcinogenic effect is supposed to be due to their normalizing action on hormonal metabolic and immunological shifts arising in the body after transplacental administration of the carcinogen.

[An experimental study of the possibilities of using pentoxifylline for the prevention of cancer at different sites]. / Eksperimental'noe izuchenie vozmozhnostei primeneniia pentoksifillina dlia profilaktiki raka ralichnykh lokalizatsii.

Three models of cancerogenesis were used to test the anti-cancerogenic effects of pentoxiphylline. In female rats, breast adenocarcinoma was induced by intramammary injections of N-methyl-N-nitrosourea (MNU) or colonic and rectal adenocarcinomas by intrarectal instillations of MNU. In female mice, squamous cell carcinomas of the cervix uteri and vagina were induced by intravaginal applications of 7,12-dimethyl-benz(a) anthracene (DMBA). Pentoxifylline was given with drinking water at a concentration of 500 mg/l long at the stage of carcinogenesis promotion/progression. Pentoxifylline exerted a strong inhibitory effect on the development of mammary tumors and a moderate inhibitory effect on the development of colonic and rectal tumors induced by MNU in rats. However, the drug did not affect the development of cervical and vaginal tumors caused by DMBA in mice.

[The inhibiting effect of ortofen and indomethacin in relation to the development of induced nervous system tumors in rats]. / Tormoziashchii éffekt ortofena i indometatsina v otnoshenii razvitiia indutsirovannykh opukholei nervnoi sistemy u krys.

The anticarcinogenic effects of the nonsteroidal antiinflammatory drugs ortophen and indomethacin on carcinogenesis of the nervous and renal systems were studied. Glial tumors of the brain and spinal cord, neurinomas of peripheral nerves and renal mesenchymal tumors were induced in rats through a single transplacental administration of N-ethyl-N-nitrosourea, 75 mg/kg body weight. Ortophen and indomethacin each used in a dose of 20 mg/litre of drinking water in the period of postnatal life were effective in inhibiting the growth of brain and spinal cord tumors, showed a statistically insignificant tendency to suppress the growth of peripheral nervous tumors, but failed to affect the growth of renal tumors.

[Characteristics of the action of N-nitrosoethylurea in rat embryogenesis]. / Osobennosti deistviia N-nitrozoétilmocheviny u krys v émbriogeneze.

Based on the experiments with single intravenous injections of NEU in rats with definite pregnancy terms, it was found the embryos are especially sensitive to embryotoxic effects at the 3d--4th and 9th day, to teratogenic effects--at the 9th--14th day. The carcinogenic effect of NMU (20 mg/kg) is evident following the exposure, starting from the 11th day of embryogenesis, and the former is equally maximum during the subsequent terms until the end of the intrauterine period, their offsprings developing multiple tumors of the central and peripheral nervous systems. The sensitivity of rat embryos to NMU carcinogenic effect, contrary to the embryotoxic and teratogenic ones, showed no strict staging character. No correlation was noted between gross developmental defects and the appearance of tumors.