Structural myocardial reorganization and changes in the blood lipid spectrum in rats were studied after administration of a single sublethal dose of doxorubicin (15 mg/kg) alone and in combination with atorvastatin (20 mg/kg/day over 7 days). It was established that doxorubicin induced the development of dyslipidemia in experimental animals (the concentrations of total cholesterol, triglycerides, and VLDL increased by 2.2, 2.0, and 1.96 times, respectively; the atherogenic coefficient increased by 3.4 times by day 7 of the experiment). In animals with experimental anthracycline cardiomyopathy treated with atorvastatin, the concentrations of the main components of the blood lipid spectrum increased less markedly. Atorvastatin alone induces moderate myocardial remodeling in comparison with more pronounced changes in the structural organization of the myocardium in rats treated with doxorubicin alone. Course treatment with atorvastatin under conditions of doxorubicin-induced cardiomyopathy reduced the severity of myocardial remodeling: the decrease in the volume density of cardiomyocytes and the increase in the volume density of the connective tissue were less pronounced in the dynamics of the experiment.

The prostatotropic activity of glycyrrhizic acid disodium salt (Na2GA) was studied in the models of benign prostatic hyperplasia (BPH) induced by chronic injection of sulpiride (40 mg/kg intraperitoneally for 8 weeks) or testosterone propionate (20 mg/kg subcutaneously for 4 weeks) in the Wistar rats. The oral administration of Na2GA in a dose of 100 mg/kg produced a moderate antiproliferative effect in both BPH models resulting in reduced volume density of prostatic epithelium (in the testosterone model) and increased volume density of the glandular lumen (in both models). The observed prostatotropic effects of Na2GA were similar to those of Permixon and finasteride, but they were less pronounced as confirmed by smaller drops in epithelial volume density and epithelial-to-stromal ratio compared to the effects of both reference drugs.

We studied dynamic changes in the total number of cardiomyocytes and the character of structural lesions in the myocardium in rats with modeled anthracycline-induced cardiomyopathy provoked by a single injection of doxorubicin in a dose of 10 mg/kg alone or in combination with subsequent adrenergic stimulation. The injections of epinephrine during the development of anthracycline-induced cardiomyopathy resulted in more pronounced loss of body weight, stronger decrement of the heart weight, and more severe decrease of the cardiomyocyte count in comparison with the corresponding changes induced by doxorubicin alone. The basic lesions of cardiomyocytes in anthracycline-induced cardiomyopathy are the lytic alterations and subsegmental contractures; in contrast, combined use of doxorubicin and epinephrine provoked degree II and III contractures. The revealed necrobiotic changes of cardiomyocytes resulted in their death and pronounced decrease of their number at the initial terms of the study. Hypertrophy observed at later terms of the experiments in parallel with partial recovery of cardiomyocyte number reflected the development of regenerative and adaptivecompensatory processes induced by massive death and elimination of the parenchymatous cells (up to 36-37% of population).

Prostatotropic activity of (3,5-dimethyl-4-hydroxy)benzyl thiododecane (T-DD) was evaluated on a model of benign prostatic hyperplasia induced in Wistar rats by chronic (2 months) intraperitoneal administration of sulpiride (40 mg/kg). Morphometric analysis of the dorsolateral lobe of the prostate showed that after the 2-month course of intragastric T-DD (100 mg/kg) administered in parallel with sulpiride, the volume density of glandular epithelium decreased by 1.7 times, while the volume density of prostate stroma increased by 2 times. After administration of the reference drug Permixon at a dose of 50 mg/kg, the volume densities of epithelium decreased by 1.3 times and stromal volume density increased by 1.5 times. The observed effects are presumably related to suppression of 5α-reductase activity and modulation of estrogen receptors in the prostate.

The study examined the myocardial ultrastructural alterations in rats maintained on various atherogenic diets. It revealed the complex ultrastructural alterations of cardiomyocytes and endotheliocytes (including the lytic and destructive changes of the intracellular organelles, upregulation of the autophagocytosis in the cardiomyocytes, and necrobiosis with apoptosis of endotheliocytes) reflecting the cytopathic features of circulating cholesterol and lipoproteins, whose elevation determined the intensity of destructive processes. The revealed peculiarities in the changes of lipid inclusions (their osmiophilic transformation) in cardiomyocytes can be provoked by entry of cholesterol into the cells and its further metabolic modifications. During moderate dyslipidemia, the cardiomyocytes demonstrated the ultrastructural signs of induction of intracellular regeneration (marked with the clusters of polysomes in the intermyofibrillar and subsarcolemmal spaces with appearance of neogenic myofilaments) and upregulated pinocytotic activity. In all cases, up-regulated autophagocytosis in cardiomyocytes was accompanied by accumulation of myelin- and vacuole-like structures in the intercellular spaces and capillary lumens paralleled with appearance of activated forms of macrophages and fibroblasts in the myocardium.

Morphological analysis of the subcutaneous fat was performed in rats after subcutaneous implantation of basic dental plastic materials with different hydrophobic and hydrophilic properties. It was shown that subcutaneous implantation of dental plastics with mostly hydrophobic surface and low biocompatibility induced destructive and inflammatory processes of various intensities, sometimes with allergic component; morphological signs of processes persisted for 6 weeks. Modification of basic plastics using glow-discharge plasma and enhancement of their hydrophilicity and biocompatibility significantly reduced the intensity of destructive and inflammatory processes and ensured more rapid (in 2 weeks) repair of the destroyed tissues with the formation of fibrous capsule around the implant.

РОЛЬ РЕЦЕПТОРА-2 VEGF (KDR/Flk-1) В КАРДИОМИОГЕНЕЗЕ И ЦИТОПРОТЕКТОРНЫХ РЕАКЦИЯХМешков И.О., Новоселова Е.И., Бушманова Г

The influence of Opisthorchis felineus invasion on the development of pathological changes in the hepatobiliary system was studied in 120 golden hamsters in a long-term experiment (42 weeks) after single infection per os in the dose of 50 metacercariae per animal. The animals were sacrificed on weeks 4, 8, 12, 16, 28 and 42. Chronic experimental infestation with O. felineus triggered a cascade of morphogenetic processes in both extrahepatic and intrahepatic biliary systems. At the early stages of the experiment, polyps and strictures of bile ducts were formed in the lobar bile ducts; in portal tracts, hyperplasia and adenomatous transformation of the newly formed epithelial structures were observed. At the later stages, third-degree biliary intraepithelial neoplasia developed in the lobar bile ducts; in the intrahepatic bile ducts, increased epitheliocyte hyperplasia and invasive growth of cell cords were observed, that impaired tissue architectonics. Progressing cell atypia can be classified as cholangiocellular cancer.

Проведен сравнительный анализ электрических потенциалов кожи лица и чувствительности пульпы зубов у здоровых испытуемых-добровольцев и больных с травмами верхней и нижней челюсти. Установлено значительное возрастание уровня потенциалов кожи до 20 % на стороне травмы. Степень различия в уровне потенциалов кожи в симметричных точках обусловлена выраженностью клинических проявлений и отражает характер течения патологического процесса при травматических повреждениях нерва. Показана сопряженность процессов восстановления проводимости тройничного нерва и снижения уровня электрических потенциалов кожи. Патоморфологический анализ изменений нижнего альвеолярного нерва при травматических повреждениях проведен в различные сроки после травмы. Преобладание процессов альтерации нервных волокон наиболее было выражено в период от 10 до 14 суток. Признаки репарации поврежденных структур обнаруживали спустя месяц после травмы. Оценка электрофизиологических показателей кожи лицевой области может служить дополнительным, атравматическим методом мониторинга проводимости периферических ветвей тройничного нерва в процессе реабилитации после травмы, что позволяет оценить нарушения функционирования тройничного нерва, не прибегая к неприятной для пациента процедуре.

Toxic liver injury with the development of fi brosis and cirrhosis was modeled in Wistar rats by intragastric administration of 0.1 ml/kg CCl4 in combination with 5% ethanol with glucose 3 times a week for 6 weeks. The animals were treated with betulonic acid amide (50 mg/kg in Tween aqueous solution) and heptral (6 mg/kg) as hepatoprotective compounds. It was found that betulonic acid amide stimulated the regenerative response in hepatocytes under conditions of combined toxic exposure and promoted recovery of their qualitative and quantitative characteristics, which was accompanied by a signifi cant decrease in the severity of liver fi brosis and the absence of cirrhotic transformation of the liver.

PT/Y mice used for studies of the effects of mutagens are characterized by the absence of spontaneous tumors of the liver, but often develop these tumors in response to chronic o aminoazotoluene treatment. The level of glucocorticoid induction of adaptive hepatic enzyme tyrosine aminotransferase decreases by more than 70 % 24 h after acute injection of o -aminoazotoluene to these animals. These mice can serve as a model for studies of the relationship between the effect of carcinogens on the regulation of activity of adaptive hepatic enzymes and their capacity to induce the development of liver tumors.

Results of long-term prospective follow-up of patients with early stages of mitral and aortic valvulitis and primary chronic septic endocarditic are presented. Clinical diagnostics of the diseases is described and the key role is assigned to pathognomic (absolute) clinical symptoms. The tendency to progressive fibrosis of endocardial structures with subsequent gradual development of valve dysfunction and stenosis (especially for the mitral valve) is revealed. It is shown that early treatment increases the effective valve area and promotes reversion of mitral stenosis. The possibility of early diagnostics of primary chronic septic endocarditis in combination with adequate etiopathogenetic therapy provide the basis for prevention of acquired valvular disease.

Представлен научный обзор по вопросу применения биоимпедансного анализа в диагностических целях и в эксперименте. Показано, что измерение с помощью накожных электродов электрического импеданса позволяет получать информацию, не внося в организм изменений или риска развития осложнений. Биоимпедансные измерения дают возможность оценки широкого спектра морфологических и физиологических показателей. Они основаны на наличии закономерностей, связывающих значения импеданса с параметрами компонентного состава тела и позволяют исследовать динамику и перераспределение жидкости между его регионами в результате действия физических и физиологических нагрузок и в случае патологий. Анализ состава тела по показателям импеданса помогает контролировать состояние липидного, белкового и водного обмена организма. В этой связи он представляет интерес для практической медицины. По показателям электропроводности тканей можно оценить энергетический статус организма спортсмена и прогнозировать его результативность. Метод может легко адаптироваться к условиям эксперимента – расположение отводящих электродов на поверхности тела позволяет оценить параметры конкретного его участка in vivo.

The changes in mammary gland bioimpedance were examined in the dynamics of the inflammatory process. Bioimpedance of affected gland was 2-3-fold lower than that of the contralateral one; normally, this difference did not exceed 10%. The phases of inflammation development were paralleled by changes in bioimpedance. During wound epithelization, impedance increased and approximated the normal level. Further increase of bioimpedance by more than 30% and its stabilization at this level attested to recurrence of inflammation, while its irreversible drop indicated devitalization the tissues. The diagnostic criterion attesting to the development of local inflammatory reaction is deviation of bioimpedance in the impaired area by more than 15% from that of the adjacent intact site.

Проведен анализ поляризационных свойств тканей внутренних органов трупов лабораторных животных с учетом фактора прижизненной алкогольной интоксикации. Показано, что изменения коэффициента поляризации (Кп) тканей трупов относительно тканей интактных животных и животных, подвергавшихся при жизни стрессирующему воздействию алкогольной нагрузки, в первые сутки после смерти имеют общую тенденцию к снижению, изменяются только численные значения показателей. Кп тканей внутренних органов в течение первых суток постмортального периода остается выше единицы, что свидетельствует о частичной сохранности структуры тканей. Прижизненная алкогольная интоксикация способствует более раннему разрушению структуры тканей. Органы, более чувствительные к воздействию алкоголя: сердце, надпочечник, селезенка, значительнее страдают от литических изменений. Эти факты следует принимать во внимание при определении по показателям электроимпедансометрии срока давности наступления смерти, степени алкогольной интоксикации и сохранения жизнеспособности образцов тканей трансплантируемых органов.

The hepatoprotective effects of new triterpene derivatives, betulin 3β,28-di-O-nicotinate (of3) and 3,20-dioximino-29-norlup-28-ic acid methyl ester (of15), were studied in CBA/Lac mice with transplanted RLS lymphoma receiving polychemotherapy and without it. Injection of of3 and of15 agents to animals with tumors receiving polychemotherapy reduced the severity of toxic involvement of the liver, reduced mitotic activity of tumor cells in the primary node in animals receiving and not polychemotherapy, and produced a moderate antitumor effect. These effects were more pronounced for of15 agent. In addition, injection of agents of3 and of5 to animals with transplanted RLS lymphoma reduced the intensity of alterations associated with the total systems and local effects of the neoplastic process.

We studied hepatoprotective activity of betulonic acid and its alaninamide on the model of combined CCl(4)- and ethanol-induced toxic liver damage in rats. The test substances, especially betulonic acid alaninamide, considerably reduced the elevated biochemical parameters in animals with toxic liver damage. Betulonic acid alaninamide also stimulated reparative processes in the liver (activated hepatocyte proliferation). Heptral (reference drug) produced no appreciable effects on the reparative processes. Our findings suggest that betulin derivatives exhibit pronounced protective properties.