[CHANGES IN THE BRAIN TESTOSTERONE METABOLISM AND SEXUAL BEHAVIOR IN MALE RATS PRENATALLY EXPOSED TO METHYLDOPA AND STRESS].

The changes of aromatase and 5α-reductase activities were studied in preoptic area (POA) and medial basal hypothalamus of 10-days-old and sexual behavior in 3-month-old male offsprings of rats exposed daily to noradrenaline antagonist methyldopa (400 mg/kg per os) 30 minutes prior to 1-hour immobilization during the last week of pregnancy (from 15th to 21st day). Prenatal stress caused aromatase activity lowering in the POA of developing brain and feminization (appearance of lordosis) and demasculinization of sexual behavior (prolongation of latent periods to the first mounting and first intromission as well as of the first ejaculation and postejaculation refractory period) in young male offspring. Oral methyldopa used prior to pregnant females stressing prevented early effect of prenatal stress on aromatase activity in the POA and normalized the male sexual behavior in young male rats by shortening both latent period to the first ejaculation and postejaculation refractory period, and an increase of numbers of ejaculation. The data obtained indicate that brain noradrenergic system plays significant role in the mechanisms of metabolic- and behavioral disturbances developing in male rats exposed to prenatal stress.

Hormonal impact on tumor growth and progression.

In this review, current knowledge of hormones impact on prostate, breast and endometrium cancer growth and transition to hormone therapy resistant phenotype is summarized. A special consideration is given to genetic alterations and hormone responsive signa-ling pathways. Estrogen, androgen and progesterone are the key drivers in these cancer variants. Hormone receptors and their interplay with plenty of growth factors generated by the tumor microenvironment contribute greatly to carcinogenesis and cancer cell proliferation. The tumor cell plasticity that could explain a loss of responsiveness to hormone deprivation therapy and aggressive course of the diseases has been addressed.

Assessment of gold nanoparticle effect on prostate cancer LNCaP cells.

UNLABELLED: In recent years gold nanoparticles (AuNPs) have received considerable attention for various biomedical applications including diagnostics and targeted drug delivery. However, more research is still needed to characterize such aspects of their use in clinical oncology as permeability, retention and functional effect on tumor cells. AIMS: This study was designed to describe the effect of non-functionalized AuNPs on LNCaP prostate cancer cells growth. MATERIAL AND METHODS: LNCaP cells were cultured in RPMI-1640 medium containing AuNPs covered by polyvinylpyrrolidone of average size 26.4 nm (10.0 µg/ml). Counts of cells were calculated and their morphology was examined. RESULTS: AuNPs conglomerates have been visualized in cultured cells. After 4-day incubation in presence of AuNPs significant retardation of LNCaP cells growth was observed both in 5α-dihydrotestosterone stimulated and non-stimulated cultures. No morphological changes of live LNCaP cells were seen in any experiment. CONCLUSION: Given absence of morphological changes in live cells and dribble and relatively constant numbers of dead cells, it was concluded that inhibitory effect of AuNPs on LNCaP cells growth was caused by alterations of proliferation.

[First experience of supraclavicular flap application for the closure of defects localized in the lower third of the face and neck].

First experience of the supraclavicular flap transposition for closure of superficial, but extended, defects of the soft tissues in the lower third of face and neck region in 6 patients is presented. In all the patients good functional and cosmetic result was achieved.

Cooperative antitumor effect of endothelial-monocyte activating polypeptide II and flutamide on human prostate cancer xenografts.

UNLABELLED: Recombinant cytokine-like endothelial monocyte-activating polypeptide II (EMAP II) and antiandrogen flutamide target different mechanisms of growth of androgen-dependent prostate cancer (PC). The aim of this study was to clarify whether combined treatment with EMAP II and flutamide is more effective than monotherapy with regard to retardation of PC progression. MATERIALS AND METHODS: Antitumor effects of EMAP II (10 µg/kg b.w./d, s.c., 3d), or flutamide (10 mg/kg b.w./d, per os, 3d), or their combination were studied in CBA male mice bearing human androgen-dependent PC xenografts for 7 days. Androgen-dependent phenotype of the tumors was verified in preliminary castrated mice. The xenografts were weighed and underwent a histopathologic examination. The results were compared with those of non-treated mice. RESULTS: EMAP II and flutamide used separately inhibited growth of the xenografts by 74% and 53% respectively. Both drugs caused destructive changes in malignant epithelial cells along with leukocyte infiltration of the tumor. Combined treatment inhibited tumor growth by 85%, and was more effective than monotherapy with regard to morphological changes. CONCLUSIONS: This study demonstrates cooperative inhibitory effect of EMAP II and flutamide on growth and morphology of human PC xenografts that could represent a new modality of palliative treatment of this disease.

[Cardiotoxic effects of breast cancer chemotherapy and their possible correction].

Clinical data are reported upon the examination of a group of 160 women aged 18-55, suffering of a breast cancer and subjected to polychemotherapy using various cytostatic schemes: (I) standard CAF scheme, course repetition each 4 weeks; (II) alternating CAF and AVCFM schemes (intermittent introductions), a total of 4 courses. For the reduction of the cardiotoxic effects of anthracyclines, one part of patients was given an antioxidant preparation of amber acid--Reamberin--whose administration substantially decreased both the frequency of cardial complaints and the expression of clinical manifestations of the astheno-neurotic syndrome and prevented the occurrence of systolic and diastolic dysfunction of myocardium and the heart rhythm and conductivity disturbances.

[Bioethical aspects of experiments on the animals].

The principles of humane attitude toward laboratory animals, the main rules of defense and application of vertebral animals in scientific investigations, which are coordinated with European convention content, were presented. Recommendations for organization and activities of bioethics committees and commissions, which conduct the expert estimation of scientific investigations, using laboratory animals, were presented.

Prenatal dexamethasone prevents early and long-lasting neuroendocrine and behavioral effects of maternal stress on male offspring.

The hypothesis on the mediating role of hypothalamic-pituitary-adrenocortical (HPA) hormone secretion in neuroendocrine, neurochemical and behavioral alterations generated by prenatal stress in male rat offspring was tested in this study with dexamethasone (Dex) used for suppression of HIPA stress responses. Pregnant dams were being restrained daily for 1 h over the last week of gestation. In male offspring this resulted in attenuation of sex-specific pattern of the protein fractions (on the 5th postnatal day), steroid aromatase activity (on the 10th postnatal day) in the brain preoptic area, and in a decrease of male copulatory behavior, hypothalamic noradrenaline and plasma corticosterone responses to an acute stress, an increase in HPA responses to noradrenergic stimulation and other effects in adulthood. All those changes were prevented with prenatal Dex in a dose of 0.1 mg/kg b.w. injected 30 min prior to restraining pregnant dams. As such, HPA hormone secretion mediates alterations of programming of brain development induced by prenatal stress.

[Possibilities of reconstructive plastic surgery in the treatment of vascular malformations of the head region].

Results of treatment of 19 patients, suffering vascular malformation of the head region, were analyzed. Application of a new highly informative diagnostic methods of surgical intervention differential methods have promoted significant clinical improvement.

[Autotransplantation of composit complexes of tissues for restoration of the combined bone-soft tissue post-traumatic defects of the wrist and the hand].

The experience of treatment of 27 patients, suffering the extended bone-soft tissue defects of the wrist and the hand was summarized. In 12 patients (1-st group) the bone plasty was performed, using nonvascularized fragment of os ilei wing with simultaneous excision of the damaged soft tissues and free transplantation of m. latissimus dorsi or m. serratus anterior flaps. In 15 patients (2-nd group) autotransplantation of m. serratus anterior flap, including the vascularized costal fragments in its content, was performed. The musculo-costal flap application had appeared a perspective procedure while restoration of carpal bones defects. Plastic properties of such a transplant are relative technical simplicity of its mobilization, minimal aesthetic defect in the donor zone, possibility of creation of a necessary long vascular pedicle, tolerance of the complex to infection, what secures the expediency of its application in reconstructive plastic surgery.

Antitumor effect of endothelial monocyte-activating polypeptide-II on human prostate adenocarcinoma in mouse xenograft model.

UNLABELLED: Endothelial monocyte-activating polypeptide-II (EMAP-II) is a novel proinflammatory cytokine with anti-angiogenic properties. The aim of this work was to evaluate in vivo antitumor activity of EMAP-II in growing human prostate adenocarcinoma xenograft mouse model. MATERIALS AND METHODS: Recombinant human EMAP-II was expressed in Escherichia coli and purified after cleavage with enterokinase (EMAP-II e). EMAP-II preparations were injected to CBA mice bearing subrenal capsule xenografts of human prostate adenocarcinoma. After 3-days treatment, the xenografts were isolated and weighed, then the transplants exposed to EMAP II e (100 or 200 microg/kg b. w.) were examined histologically. RESULTS: EMAP-II administered daily at a dose of 100 or 200 microg/kg b. w. caused striking retardation of local tumor progression as compared to the controls. Low dose (10 microg/kg) was effective in some cases. CONCLUSION: EMAP II exhibits significant antitumor activity in vivo in human prostate adenocarcinoma xenografts in mouse model.

[Sex characteristics of neuroendocrine effects of prenatal exposure to exogenous glucocorticoids].

The effects of hydrocortisone acetate treatment of rats during the last gestational week on neurochemical and morphological characteristics of the brain in early postnatal and mature offspring were studied. Disappearance of sexual differences both in aromatase and 5alpha-reductase activities and noradrenaline concentration in the preoptic area in 10-day old rats was found. Meanwhile a sexual dimorphism in serotonin metabolism emerged. In adult offspring, the prenatal exposure to glucocorticoids resulted in disappearance of sexual differences in neurocytes' nuclei volume in medial preoptic and suprachiasmatic nuclei. The adrenocortical reaction to noradrenaline infusion to the 3rd brain ventricle was absent in the experimental males and intensified in females. In males, adrenocortical reaction to restraint decreased while post-stress changes in hypothalamic noradrenaline concentration and hippocampal glutamate decarboxylase activity were not observed. In the similar experiments in females both the augmentation of adrenocortical reaction and inhibition of GABA-ergic system were revealed. The results obtained indicate the modifying effect of prenatal exposure to glucocorticoids on sexual dimorphism of neuroendocrine system.

[Surgical treatment of inveterate defects of the hand II-V fingers extensors tendons in VI-VII zone].

Possibilities and efficacy of secondarily restoration of inveterate defects of the extensors tendons of fingers, owing various extent, were studied in conditions of cicatricial changes in the hand back skin. There was established, that in ischemic and reperfusion damage of the hand tissues the coarse cicatricial changes in the end portions of the traumatized tendons occurs, essentially influencing surgical tactics. Optimal operative techniques, directed on the extensors tendons restoration in various extent of their defects and various severity of the soft tissues changes in the hand back were determined. There was shown the perspective character of substitution of the cicactricially transformed hand back soft tissues and significant defect of the II-V fingers extensors tendons using vascularized compound complex of tissues of the foot back flap with the tendon complex.

[Transplantation of the muscular perforant flaps for restoration of tissues defects in the extremities].

There was summarized the experience of surgical treatment of 9 patients with the soft tissues defects of various etiology, localization and size, in whom microsurgical autotransplantation of the perforant flaps was performed on thoracospinal and medial gastrocnemial arteries. Peculiarities of preparation and mobilization of perforating vessels, securing the motor nerves branches, were presented. The perforant flaps advantages are: their small thickness, plasticity, mobility and minimal complications in the donor's zone. The perforant flaps advantages secure the wider diapason of their usage comparing with conventional composed complexes of tissues.

[Surgical tactic in the injury of neck vessels]. / Khirurgicheskaia taktika pri povrezhdenii sosudov shei.

Retrospective analysis of the surgical treatment results in 50 injured persons with the damage of the neck vessels in 1998-2003 yrs period was presented. Restorational-reconstructive operations were performed in 19 (38%) injured persons with the arteries damage, in 10 (20%)--with the veins damage, the ligature operations were done, accordingly, in 6 (12%) and in 20 (40%). Satisfactory result was noted in 41 (82%) injured persons. Neurological complications had occurred in 4 (8%) of patients. Mortality had constituted 10% (5 patients died). The principles of surgical treatment of the neck vessels damage were stated.

[Surgical treatment of injured persons with the main blood vessels damage]. / Khirurgicheskoe lechenie postradavshikh s povrezhdeniem krupnykh krovenosnykh sosudov.

Retrospective analysis of the surgical treatment results of 45 injured persons with damage of main blood vessels was presented. Specific operative methods in injury of the different type main blood vessels, localized in thoracic and abdominal cavities, were depicted. In 35 (77.8%) injured persons good and fair results of restoration operations were noted. The lethality rate was 22.2%. The tactic of surgical treatment of the main blood vessels injury was presented.

Developmental changes in the distribution of corticosteroid-binding globulin in fetal and newborn sheep tissues.

Developmental changes in immunohistochemical localization of corticosteroid-binding globulin (CBG) in fetal and newborn sheep tissues were studied. Tissue samples have been harvested at days 63-64, 100-103, 125-128 and 142-144 of gestation or 2 postnatal days. In the liver, immunoreactive CBG (irCBG) has been identified in hepatocytes. The intensity of CBG staining was highest at 63-64th gestation days and then was lowered gradually down to negligible level in newborn lambs. Within kidney, irCBG was selectively localized to the epithelium of proximal and distal convoluted tubules. Its amount in the course of development followed a pattern similar to that in the liver. By contrast, fetal sheep lung and pancreas demonstrated noticeable rise of irCBG late in gestation. irCBG has been detected in respiratory epithelium of tertiary bronchi, bronchioles and terminal bronchioles, meanwhile alveoli and other lung tissues were CBG-immunonegative. In the pancreas, irCBG staining was associated with acinary cells, whereas Langerhans islets contained no irCBG at all examined stages of pregnancy. Developmental changes in irCBG did not follow reported triphasic profile of fetal sheep plasma CBG concentrations thereby showing the existence of independent cellular mechanisms regulating CBG level in the tissues. Peculiarities of intraorgan distribution and developmental changes in irCBG suggest that intracellular CBG may regulate bioavailable cortisol concentrations in the sheep tissues during fetal and early postnatal life.