Perifocal Zone Research Articles

Role of fibrinolysis and α2-macroglobulin in growth of primary adenocarcinoma and rectal polyps.

e15093 Background: An important role in tumor angiogenesis induction is played by hydrolytic systems, in particular plasmin one which provides degradation of the extracellular matrix, activates growth factors and metalloproteinases. Our purpose was to analyze the tissue fibrinolytic system and α2-macroglobulin (α2M) in primary adenocarcinoma (PA) and polyps (P) of the rectum (R). Methods: Tissues of tumors (РА, G2, T2-3N0M0, 42-73 years) and their perifocal zone (PZ) in R (n = 24) and Р (n = 27) were studied by ELISA; the result was calculated per 1 mg of tissue. Results: Resection line (RL) tissues contained levels of tРА antigen and its active form (tРА-Ag and tРА-act) 6.7 and 33.8 times higher than prourokinase and urokinase levels (uPA-Ag and uPA-act). RL tissues in P did not differ significantly from R tissues at PA resection. uPA-act in PA was higher than in RL by 3.2 times, uPA-Ag - 8 times higher, tРА-act - 2.3 times lower; tPA-Ag was similar to RL tissue values. Plasmin-α2-antiplasmin complex (PAP) in PA was 1.4 times higher than in RL. Plasminogen (PG) in PA was 1.5 times lower than in RL (p < 0.01). Activity of α2M in PA and RL did not differ. PAP and α2М in PA PZ were similar to RL, and PG did not differ from PA. Other indices were between tumor and RL levels. P tissue did not show changes in uPA; tPA-act activity was 1.3 times lower than in RL, and tPA-Ag 1.3 times higher (p < 0.01). PAP in tissues of 88.2% P was 1.5 times higher than in RL and 1.7 times lower than in PA. PG and α2М were similar in P and RL. PAP in PZ of P was 2.3 times higher than in RL and 1.5 times higher than in PA PZ. PG in P PZ was 1.4 times lower than in RL (p < 0.01). α2М activity in P PZ was higher than in RL and P by 5.4 times on average. uPA in P PZ did not differ from RL; tРА-Ag and tРА-act were higher than in RL by 1.5 and 1.9 times and exceeded P by 2.1 and 1.5 times (p < 0.01). Prevalence of uPA, activation of PG in PA and its PZ indicated degradation of the extracellular matrix compared with the corresponding P tissues. Conclusions: The role of R tumor PZ as a "metabolic" tumor field in neoplasm progression was confirmed. Activation of fibrinolysis in PA and its PZ with a deficiency of inhibitors stimulates the migration and proliferation of cells. Increasing tРА, РАР and α2М in PZ of polyps has a protective effect.

Differences in plasminogen activation in primary rectal adenocarcinoma with and without liver metastasis.

e15111 Background: Plasminogen activators play a key role in the cascade fibrinolytic system as they catalyze plasmin formation from plasminogen (PG). Plasminogen activators together with plasmin are directly or indirectly involved in tumor growth. The purpose of the study was to compare the plasminogen activation system in primary adenocarcinomas (РА) of the rectum (R) with and without liver metastases (LM). Methods: Tissues of tumors (РА, st. III, G2, 38-74 years) and their perifocal zone (PZ) with LM (T2-3NхM1, n = 24) and without them (T2-3N0M0, n = 32) were studied by ELISA. Results: The studied parameters did not differ in apparently intact R tissues in the resection line (RL) with and without LM. Plasmin-α2-antiplasmin complex (PAP) was 1.4 times higher in PA with LM than without LM (p < 0.05). Prourokinase and urokinase levels (uPA-Ag and uPA-act) were 12.4 and 3.7 higher than in RL. uPA-Ag and uPA-act in PA+LM were higher than without LM by 1.4 and 1.6 times. PG levels and α2-macroglobulin (α2M) activity in PA+LM were lower by 1.5 and 2.7 times than in PA without LM and lower than in RL (p < 0.01). All studied parameters, except α2M, in PA+LM were activated more than in PA without LM. Low α2M content supposed realization of effects of uPA and plasmin in insufficient inhibitory control. Most parameters in PZ+LM were between the levels in PA and RL being significantly different from both and significantly exceeding the values in PZ of PA without LM. α2М was an exception being 1.8 times lower in PZ of PA+LM than in PZ of PA without LM. The results demonstrated higher uPA and РАР levels in PA and its PZ with LM than without them, with increased PG consumption and decreased α2M activity in these parts of the rectum. Activation of plasminogen system in tissues of PA+LM and in PA without LM was unidirectional. Conclusions: Levels of uPA and PAP, as well as low α2M content in PA and PZ with LM can be used as an indicator of tumor metastatic activity.

Immunocytochemical and morphometric changes in astroglial cells in the perifocal zone of the cerebral infarction model

Introduction. The perifocal zone of cerebral infarction contains dying and reactively altered neurons whose fate depends on the type of intracellular interactions and, in particular, on the response of astrocytes partaking both in neuronal damage and neuroprotection. The features of the response of astrocytes to ischemic injury and the role of their activation in gliosis have been studied insufficiently. Objective. To evaluate the changes in astroglia in the perifocal zone of cerebral infarction depending on its reproduction time by immunomorphology and computerassisted morphometry. Materials and methods. Infarction was induced in the left hemisphere of rat brain cortex (n=10) by middle cerebral artery occlusion. Astrocyte distribution and shape were assessed on day 3 and 21 after surgery; localization of gliofibrillar acidic protein (GFAP), aquaporin 4 (AQP4), and glutamine synthetase (GlnS) in the perifocal zone was measured. Results. Astrocyte shape and distribution, as well as GFAP expression, significantly altered depending on time that has passed since the infarction and distance to the injury focus. On day 3, the area occupied by astrocyte processes decreased by 15% of the control value, while increasing by 35% on day 21. Expression of GlnS and AQP4 near the infarction focus decreased on day 3, while opposite changes were observed on day 21. Redistribution of the studied proteins in processes of reactive astrocytes was also detected. Two morphological types of astrocytes were differentiated: the scarring polarized astrocytes, which were characterized by redistribution of marker proteins in processes, and the moderately altered transiently activated ones. Conclusions. Astrocytes were found to be heterogeneous in the perifocal zone of cerebral infarction; a dependence between changes in their structure and function and the distance to the injury focus and time that passed after the infarction was revealed. The scarring and transiently activated astrocytes, which play different roles in remodeling and repair of ischemic neural tissue in the perifocal zone of cerebral infarction, were characterized by immunohistochemical and morphometric analysis.

CHARACTERISTICS OF STEROID METABOLISM IN MALE RATS AT STAGES OF EXPERIMENTAL LIVER METASTASIS

The aim of the study was to reveal characteristics of steroid metabolism in tumor, metastases, adrenal glands (AG) and blood serum (BS) in male rats in the course of liver metastasis, as well as diagnostic signs of metastases. Material and methods. The study included 44 white male rats weighing 180-250 g. S-45 sarcoma was transplanted intrasplenically. Estrone, estradiol, free testosterone, 17-OHP, cholesterol, cortisol (in tissues and BS), DHEAS (in tissues), DHEA and ACTH (in BS) were studied by the using standard test kits for ELISA and RIA. Results. We found that the pituitary gland does not participate in liver metastatic process (low ACTH in BS). AG are assumed to play a regulatory role of steroidogenesis in tissues. Characteristics of liver metastases that not re-metastasize - non-active metastases (NAM) are: decreased cortisol in the perifocal zone (PZ) and the less estrone increase in metastases. Characteristics of metastases that re-matastasize to lungs - active metastases (AM) are: increased cortisol in PZ and the greater estrone gain in metastases. Hypo-estradiolemia and hyper-testosteronemia were diagnostic criteria for the upcoming liver metastasis; hyper-estradiolemia along with the decline of free testosterone - signs of liver metastases; hyper-cortisolemia and hypercholesterolemia are for AM in experimental liver metastasis, hypo-cortisolemia and hypocholesterolemia are signs of NAM in the liver of male rats. Conclusion. Consequently, one of the detected pathogenetic mechanisms of liver metastasis is presented by deactivation of the central pituitary regulation of steroidogenesis with regulating function passed to AG which results in steroid imbalance with accumulation of estrone in metastases and multidirectional changes in cortisol levels in PZ and BS, depending on the activity of metastases.

Free and bound plasmin in esophageal tumors and surrounding tissues in men and women.

84 Background: Esophageal squamous cell carcinoma (ESCC) is 2 to 8 times more frequent in men than in women. Tumor progression is directly connected with plasmin participation in destruction of the extracellular matrix and the basement membrane surrounding tumor. The purpose of the study was a comparative analysis of plasminogen (PG), free plasmin (P) and plasmin bound in complex with α2-antiplasmin (PAP) in ESCC tissues of men (M) and women (W). Methods: ESCC tumor tissue (T) and its perifocal zone (PZ) were studied by the ELISA (19 men and 8 menopausal women aged 58-72, st II, G2, T2-3N0-1M0-1). The results were compared to the histologically unchanged tissue from the resection line (RL). PG, P and PAP were measured in 10% homogenates prepared in sterile saline, with recalculation per 1 g wet tissue). Data were processed using Statistica 10. Results: PG content in RL was 1.5 times higher in M than in W. PG in T of M was decreased by 2 times, in W by 3.3 times, in PZ of M – by 2.9 times, in W – by 2.3 times. PG in T and PZ of M was 2.5 and 1.2 times higher than in W. P content in RL of all patients was significantly lower than in other samples, but 1.4 times higher in M than in W. P in T and PZ of M was 3 and 2.5 times higher than in RL, in T and PZ of W – 3.5 and 2.8 times higher than in RL. Significant differences were observed between P levels in T (but not in PZ): 1.3 times higher in M than in W. PAP content was relatively constant in all tissues, with a slight prevalence in T and PZ of W. P/PAP ratio was elevated in all tissues compared to RL, but in T and PZ of M it was 1.4 and 1.2 times higher than in W. P/PAP in RL of M was 1.4 times higher than in W. Conclusions: The results show a higher aggressiveness of P in PZ and T of M, while P formation in T of W was less active. We reported on a higher content of PG activators in T and PZ of M, and taking into account the morbidity statistics and literature data we suppose the effect of androgens on the conditions of PG activation into P and manifestation of its biological features. P in PZ of both M and W can contribute in the expansion of a “tumor field”. P binding in PAP complex was similar in all studied tissues.

Sex steroids, sex-binding globulin, and prolactin in tissues of adenocarcinoma and esophageal squamous cell carcinoma.

79 Background: Some researchers suggest that squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus (ACE) are characterized by different pathogenesis, epidemiology and tumor biology, and therefore require different therapeutic strategies. The purpose of the study was to analyze local hormonal status in malignant esophageal tumors and surrounding tissues depending on the histogenesis. Methods: Levels of sex steroids – free testosterone (fT), estrone (E1), estriol (E3), prolactin (PRL) and sex steroid-binding globulin (SSBG) were studied by the standard ELISA methods in tumor tissue, perifocal zone and resection line of 39 patients aged 58-74 years: 27 SCC, 12 ACE, stage II, G2, pT1-2N1M0. Results: Differences were found in local hormonal content in all studied samples dependint on the tumor histotype. Levels of SSBG, PRL and E1 in ACE were higher than in SCC by 1.3, 3.3 and 1.4 times, respectively, while fT concentration was 2.4 times lower. Levels of PRL, E1 and E3 in perifocal zone of ACE compared to SCC were higher by 2.8, 3.3 and 3.1 times, and fT was 1.3 times lower. Resection line of ACE differed from that of SCC by higher tissue concentrations of SSBG – by 1.3 times, PRL – by 1.5 times, E1 – by 1.3 times, E3 – by 1.7 times and a lower level of fT – by 1.5 times. As a result, fT/E1 ratios in ACE and surrounding tissues were on average 3 times lower than in corresponding SCC samples. Conclusions: Levels of hormones in esophageal tumors and surrounding tissues depend on the histogenesis. ACE was characterized by hyperestrogenism in esophageal tissues along with a high prolactin concentration, while SCC – by hyperandrogenism with a low PRL level. Different pathogenesis of SCC and ACE was demonstrated by the fact that hormonal profile in both tumor and resection line depended on the tumor histology.

CHARACTERISTICS OF SKIN HORMONAL BALANCE REGULATION IN FEMALE MICE IN DYNAMICS OF TRANSPLANTABLE B16/F10 MELANOMA GROWTH

Background: Skin cells are capable of the local synthesis of sex and regulatory hormones which makes it an analogue of the hypothalamic-pituitary-gonadal system and facilitates independent melanoma hormonogenesis. Aims: to study the level of hormones in the tumor, perifocal zone, the skin is unaffected, and the pituitary gland in the dynamics of growth of melanoma B16/F10 in female C57BL/6 mice. Materials and methods: Changes in the local steroidogenesis in the dynamics of the growth of transplanted В16/F10 melanoma (from week 1 to week 4) were studied in 40 female С57BL/6 mice. Hormones were determined by standard ELISA methods and radioimmunoassay in homogenates of tumor, surrounding tissues and intact tissues. Results: Tumor and then surrounding tissues showed an increase in estrogens, mostly due to estrone increase, with the development of relative androgen deficiency primarily in tumor and then in the perifocal zone and in intact tissues. Conclusions: Regulation and stimulation of such changes were performed at early stages by autocrine regulatory mechanisms and cells of primary and growing melanoma, and later by the paracrine method spreading its influence on surrounding tissues and the whole body.

Plasminogen and PAI-1 activators in tissues of adenocarcinoma and squamous cell carcinoma of the esophagus

Aim. The purpose of the study was to perform the comparative analysis of the components ofplasminogen activation system - uPA and tPA, and their inhibitor PAI-1 in tissues of esophageal adenocarcinoma (EA) and squamous cell carcinoma (SCC). Tissues of removed primary both EA (n=9, st II, G2, T2-3N0-1M0-1) and SCC (n=27, st II, G2, T2-3N0-1M0-1) were studied by ELISA. Results. EA and SCC tumor tissues showed a sharp increase in both uPA forms and in PAI-1, in EA tissue there was noted a decrease in all tPA and in SCC tissue there was seen a decline in tPA-act, compared to the resection line (RL). Perifocal zone of EA showed diminished uPA-Ag, all tPA, increased uPA-act and all PAI-1, compared to the RL. uPA and PAI-1 play an important role in progression of both SCC and EA. The role of tPA requires the further studying, but in SCC perifocal zone its impact may be rather harmful than protective. tPA-Ag/tPA-act balance was increased in SCC tissue only, while in other samples it was decreased (p

Role of hormonal factor in development of primary and secondary tumorous process in the brain

Introduction. Causes of the development onset of primary malignant cerebral neoplasms have not yet been determined. Not excluded is a possibility of unfavorable effect of the environment, genetic abnormalities, changes alterations in the hormonal background as well as metabolism, ionizing radiation: possible is also the role of viral infections and injuries. One of the main most severest complications of malignant tumors remain are metastatic lesions of the central nervous system whose proportion increases as with the patients’ longlivity. Cerebral metastases of malignant tumors are encountered more often than primary neoplasms of the central nervous system. The brain is not only a hormone-dependent organ the effect of sex hormones as early the embryonic state conditions normal development of the body as a whole and controls the sex related differentiation. It is known that neurons and glyocites like gonads and adrenal glands are able to produce steroid hormones. The enzymes responsible for the synthesis of neurosteroids were detected in the brain tissue in the embryonic period of the development. The human brain is not only a hormone-dependent organ effect influence of sex hormones as early as in the embrional state conditiones normal development of the body as a whole and controls sexual gender differentiation. It is known that neurons and glyocytes like gonads and adrenal glands are able to produce steroid hormones. Enzymes responsible for synthesis of neurosteroids were revealed in cerebral tissue both in during the embryonic period of the development and in adult condition. Besides there are have been obtained large amount of data on the presence in the cerebral cells of receptors to steroidal hormones. In various periods of life the influence effect exerted by steroids on nervous cells can change the morphofunctional state of the brain and manifests as altering myelinization, neuronal growth, and differentiation of nerve cells. The present study was aimed at comparing the level of certain some hormones in tissue of glioblastomes, metastases of breast cancer into the brain and meningiomas, as well as the respective peritumoral zones. Materials and methods. Examined were samples of tissue obtained from a total of 56 patients admitted for operative treatment to our Department. Of these, 24 glioblastomas, 19 breast cancer metastases to the brain, 13 meningiomes without peritumoral edema. The histological control was carried out in all cases. The patients’ age varied form 35 to 72 years. During operative interventions we carried out removed neoplasms of the brain followed by biochemical study of the samples of tumor tissue and immediately adjoining to the tumorous foci tissue (perifocal zone). In 10 % of cytozolic fractions of tissue prepared on the potassium-phosphate buffer of pH 7.4 containing 0.15 of Tween-20 and 1 % of bovine serum albumin by means of immunoenzymatic assay (IEA) using standard test systems we determined the level of steroid hormones – cortisole, testosterone, progesterone, estradiole, estriole, prolactine (IEA, HEMA, Russia) estrone (IEA, DBC, Canada) as well as sex-steroid-binding globulin (IEA, Alcor-Bio, Russia) and hormones of adrenohypophysis – adrenocorticotropine (ACTH) and somatotropic hormone (STH). Results. The obtained findings showed that the most hormonally saturated were metastases of breast cancer. In them along with elevated levels of cortisole, prolactine ACTH and STH concentrations whose concentrations increased virtually in any proliferative process we determined growth of saturation of tissues with estrone and free testosterone on the background of decrease level of active metabolite of estrogens – estriole. Besides, disorders of the steroid metabolism also touched the perifocal zone. Presence of glioblastoma turned out characteristic of identity of tumorous tissue and the perifocal zone by the level of cortizole, which is not found observed if tumors of other genesis. In case of glioblastoms and their perifocal zones the ratio of cortizole to ACTH excedded the norm 2.1–2.5-fold. Meningiomas revealed high concentration of cortisole, ACTH, prolactine, STH, testosterone and sex-binding globulin, as well as a low level of progesterone. In the present study meningiomas turned out liders of production of prolactine and STH as well as estriolle with sufficiently low activity. However alterations of the hormonal background of meningiomas are local isolated form the rest tissues of the brain. Probably, increase of the level of prolactine and STH in tumor tissue is a marker of proliferation, but not malignant cell transformation

MULTIPLE DRUG RESISTANCE PROTEINS OF PULMONARY SOMATIC CELLS AND THEIR SPECIFIC EXPRESSION IN FIBROUS CAVERNOUS TUBERCULOSIS

Cells of the host containing special proteins-transporters, so-called proteins of multiple drug resistance (MDR proteins) can contribute to the drug resistance formation. Goal of the study: to define specific expression of gene and distribution of main MDR proteins (MDR1/Pgp, MRP1, lRP, BCRP) in the pulmonary cells in case of active tuberculosis. Materials and methods. Expression of MDR protein genes was evaluated by RT-PCR for mRNA isolated from the surgical specimen of fibrous cavernous tuberculosis patients. Localization of MDR proteins was performed by immunohistochemical staining and confocal laser microscopy. Main results. Intensity of MDR protein genes expression varies in different zones of tuberculous lesions: MDR1 and BCRP are characterized by the highest level and MRP1 gene is characterized by the minimum level. The level of lRP gene expression depends on the inflammation zone and it is maximum in perifocal zone where protein is detected in the cells of alveolar epithelium and macrophages. High expression of MDR protein genes in various parts of tuberculous lesions witnesses about the potential involvement of these proteins in the development of drug resistance to anti-tuberculosis drugs.

The local hormonal environment of tumor and perifocal zone in patients with breast cancer: data and prospects of their application

The expression of androgen receptors is maximal in the luminal subtypes of breast cancer (BC) and increases with patient age, except triplenegative cancer cases. In reproductive age and perimenopause, the local hormonal environment of breast tumor is characterized by a 1.3– 2.0-fold predominance of androgens over estrogens (p < 0.05), but in postmenopause it depends on the biological subtype of BC. Only in the reproductive period, local hyperandrogenism is associated with the low expression of androgen receptors. As reproductive function fades away, androgen receptor expression increases and, even in perimenopause, relative hyperandrogenism in the tumor is associated with the high level of their expression. Thus, in addition to the standard immunohistochemical panel, it is also necessary to take into account other determinants of tumor biological behavior and menstrual function in women, in particular the local hormonal status of the tumor in combination with the expression of sex hormones, including androgen receptors, which allows consideration of anti-androgen therapy in treating a certain category of patients with BC.

Assessment of Chronic Subdural Hematoma Perifocal Zone Microvasculature According to Perfusion Computerized Tomography Data

Assessment of Chronic Subdural Hematoma Perifocal Zone Microvasculature According to Perfusion Computerized Tomography Data

Biocompatibility of polycaprolactone and hydroxyapatite matrices in vivo

Biocompatibility of the matrix is one of the major requirements for a functional scaffold. In this study, we carried out an assessment of biocompatibility of a complex matrix composed of polycaprolactone and hydroxyapatite under in vivo conditions by examining the dynamics of cell distribution in the original scaffold, as well as the reactions to the implant by the surrounding tissues. As result of these studies, we found that, upon subcutaneous implantation of polycaprolactone and hydroxyapatite matrix in white rats, reactive changes in the perifocal zone were completely relieved by the 21st day of the experiment. The matrix was actively populated by cells of connective tissue in the period from the 7th to 21st day of the experiment. In turn, we detected intense vascularization of the scaffold starting at the 14th day after implantation. The obtained data indicate a high degree of biocompatibility of a scaffold constructed on the basis of polycaprolactone and hydroxyapatite.

LEVEL OF HORMONES IN ENDOMETRIAL CANCER TISSUE AND INTACT OVARIES ASSOCIATED WITH DIFFERENT VIRAL INFECTIONS

Oncogenic impact of transformative viruses on the risk of cancer is well known. Today there are no studies focused on the effect of widespread, often persisting infections, such as herpes simplex virus (HSV), cytomegalovirus (CMV) and chlamydial infections on the level of hormones in the reproductive organs and their role in the pathogenesis of endometrial cancer. The aim of this study is to evaluate the effect of infectious agents in the substantive and concomitant conditions on the local hormone production in tissue of uterus and ovaries in patients with cancer of the body of uterus in menopausal age.In the tumor, in perifocal zone and in unaltered ovaries in patients with cancer of the body of uterus ELISA and PCR method determines the presence of herpes simplex virus types 1 and 2, cytomegalovirus and chlamydial infection. Depending on the level of infection in the tissues the local level of saturation of sex hormones, sex hormone binding globulin, prolactin were evaluated in samples of endometrium and ovaries. The presence of infectious agents have a modifying effect on local hormone production, increasing the intensity of disorders resulting in an imbalance of steroids, estrogen metabolites disturbance ratio and strengthening prolactinemia not only in tumor tissue but also in unchanged ovaries in patients with cancer of the body of uterus.

Growth factors vascular of endothelial and receptors in the dynamic of transplantable melanoma B16/F10 development

The growth of any cancer is associated with neoangiogenesis and neolimfogenezom that gives neoplasm opportunity of autonomous development. The basic processes of these agents is the family of vascular endothelial growth factor (VEGF), represented by VEGF-A, VEGF-C, VEGF-D, its biological effects performing the interaction with tyrosine kinase receptors R1, R2 and R3. In tumor and perifocal zone intact skin of laboratory animals - mice were inoculated subcutaneously with B16 melanoma / F10 (n = 40) to study the dependence of the level of VEGF-A, VEGF-C, as well as their receptors - R1, R2 from the development of cancer. It was found that during the growth of melanoma B16 / F10 in mice lines C57BL / 6j actively implemented mechanisms of various vessels creation - angiogenesis, and vasculogenic mimicry neolimfogenesis. Thus growth factors and their receptors are synthesized not only the tumor, but also to surrounding tissues, and even remote areas of the skin from the tumor. Until the second week of melanoma tumor is a leading component for expression of growth factors and their receptors, however, for the third week - the lead passes to the perifocal area, which continues to increase as VEGF, and their receptors. Interestingly time that remote from the tumor of the skin is much more active synthesis of VEGF-C and its receptor.

Cerebrovascular resistance in patients with severe combined traumatic brain injury

Cerebrovascular resistance is an important parameter of the microcirculation. The main objective of cerebrovascular resistance is to maintain the constancy of cerebral blood flow and protect downstream vessels when changing perfusion pressure. The purpose of the study was to assess cerebrovascular resistance (CVR) in patients with severe combined traumatic brain injury (CTBI) with and without intracranial hematomas (IHs). We analyzed treatment outcomes in 70 patients with severe CTBI (42 males and 28 females). The mean age was 35.5 ± 14.8 years (min 15 years; max 73 years). All patients were divided into 2 groups, depending on the presence of intracranial hemorrhage. The first group included 34 patients without IH, and the second group included 36 patients with epidural (6), subdural (26), and multiple (4) hematomas. The GCS score was 10.4 ± 2.6 in the first group and 10.6 ± 2.8 in the second group. The ISS severity injury score was 32 ± 8 in the first group and 31 ± 11 in the second group. All patients were operated on within the first 3 days, with 30 (83.3%) patients being operated on during the first day. Perfusion computed tomography (PCT) of the brain was performed within 1-14 days after TBI in the first group and within 2-8 days after surgical evacuation of hematoma in the second group. After PCT, the mean arterial pressure was measured, and the blood flow rate in the middle cerebral artery was determined using transcranial dopplerography. Cerebrovascular resistance was calculated using the formula modificated by P. Scheinberg. Comparisons between the groups were performed using the Student t-test and χ² criterion. The mean CVR values in each group (both with and without hematomas) were statistically significantly higher than the mean normal value of this parameter. Intergroup comparison of CVR values demonstrated a statistically significant increase in the CVR level in group 2 on the side of removed hematoma compared to group 1 (p=0.037). CVR in the perifocal zone of removed hematoma remained significantly higher compared to the symmetrical zone of the contralateral hemisphere (p=0.0009). Cerebrovascular resistance in patients with combined traumatic brain injury is significantly increased compared to the normal value. Cerebrovascular resistance in the perifocal zone after evacuation of hematoma in patients with multiple injury remains significantly increased compared to the symmetrical zone in the contralateral hemisphere.

Effects of activated protein C on the size of modeled ischemic focus and morphometric parameters of neurons and neuroglia in its perifocal zone.

The effects of activated protein C (APC) on the quantitative parameters of neurons and neuroglia in the perifocal zone of infarction induced in the left hemispheric cortex were studied in two groups of rats. Group 1 animals served as control (control infarction). Group 2 rats were injected with APC (50 μg/kg) in the right lateral cerebral ventricle 3 h after infarction was induced, and after 72 h the infarction size was evaluated and the neurons and neuroglia in the perifocal zone were counted. APC reduced the infarction size 2.5 times in comparison with the control and reduced by 16% the neuronal death in the perifocal zone layer V, causing no appreciable changes in layer III, and did not change the size of neuronal bodies but increased (by 11%) the size of neuronal nuclei in layer III. The protein maintained the sharply increased count of gliocytes in the perifocal zone of infarction and promoted their growth. Hence, APC protected the neurons from death in the ischemic focus by increasing the gliocyte count and stimulating the compensatory reparative processes.

Metabolism peritumorous zone and alteration AMPAand NMDA-glutamate receptors in the pathogenesis of gliomas of the cerebral hemispheres

Examined 12 patients with gliomas of the big hemispheres of a brain. Used immunoenzyme method for semiquantitative determination of the level of autoantibodies to NR2A-subunit of NMDA- and GluR1-subunit of AMPA-receptors of glutamate. All patients were performed positron emission tomography of the brain with 2 radiopharmaceuticals: 2-[ 18 F] fluoro-2-deoxy-D-glucose and L-[methyl- 11 C]-methionine. Features of alteration of NMDA- and AMPA-receptors of a glutamate and sequence of changes of a metabolism in a perifocal zone in gliomas of the cerebral hemispheres are studied. It is shown pre-emptive increase the level of autoantibodies to GluR1- subunit of AMPA-receptors of glutamate in patients with gliomas, current with epileptic syndrome.

EXPERIMENTAL ASSESSMENT OF ESTHETIC EFFECT OF CARIESINFILTRATION IN FOCAL ENAMEL DEMINERALIZATION

Aim. To assess in experiment the possibility and expediency of using an additive color model ( RGB ) for characterization of the color of demineralized enamel and its changes after photocomposite infiltration. Materials and methods. The material to be investigated included 14 human intact teeth (labial teeth) extracted by orthodontic indications. Experimental studied were performed using the developed model of «artificial caries», experimental analysis of color characteristics of teeth –with additive model. Results. Treatment of initial dental caries with infiltration method reliably decreases color difference indices ( GM and BY ) between the infiltrated part of enamel and its perifocal zone that provides an optimal esthetic result of treatment. Conclusion. As a result of qualitative analysis of color characteristics of vestibular surface of intact tooth and «artificial» demineralization before and after cariesinfiltration, high esthetic effect of infiltration before and after cariesinfiltration was reached.

Metabolic state of perifocal zone and resection line of skin melanoma.

e19049 Background: The state of metabolism in perifocal zone and morphologically intact skin along resection line is of importance for the processes of neoplasm metastasizing and relapse, including skin melanoma. Normalization of the state of free-radical processes, first of all along resection line, and then in neoplasm perifocal zone, should be a characteristic of pathogenically substantiated neoadjuvant influence. Methods: to study activity of free-radical processes in tissue of skin melanoma relapse, its perifocal zone (PZ) (1 cm from tumour edge) and in skin along resection line (3-5 cm from tumour edge) we investigated concentration of vitamins E and A, activity of superoxide dismutase (SOD), catalase, summary peroxidase activity (SPA), and malonic dialdehyde level (MDA) in patients with skin melanoma (pT2-3N1-2M0). The study group included 54 samples after treatment (chemotherapy and radiation). Control groups: 45 samples before treatment (CG1) and 27 samples of intact skin after plastic operations (CG2). Results: After treatment MDA concentration in tumour tissue increased by 33.4% in comparison with the CG1, but remained 17.7% lower than in CG2. Average increase in concentration of vitamins E and A was equal to 1.8 times, catalase activity decreased by 30.3% in comparison with parameters before treatment (p&lt;0.05). SOD/catalase coefficient was 1.3 times higher than in the CG1, but 3.4 times lower than CG2.More manifested changes in activity of free-radical processes were observed in PZ: MDA concentration level after treatment increased by 30% in comparison with the CG1, and differed from the one in CG2 only by 10% (p&lt;0.05). Catalase activity decreased by 1.5 times and didn’t significantly differ from the corresponding parameter in tumour tissue after treatment. Normalization of concentration level of vitamins A and E without change of their ratio was observed. There was 1.6-fold increase of SOD/SPA coefficient in comparison with the CG1, however it was 2.4 times lower than CG2 (p&lt;0.05). All parameters under study along resection line after treatment didn’t significantly differ from parameters in CG2. Conclusions: The performed treatment completely restores broken metabolism in skin along resection line, partially–in tumour perifocal zone.