[Diagnostic and prognostic significance of the level of IgM antibodies to myelin basic protein in children with traumatic brain injury]. / Diagnosticheskoe i prognosticheskoe znachenie urovnya antitel k osnovnomu belku mielina v krovi detei s cherepno-mozgovoi travmoi.

OBJECTIVE: To study the content of antibodies to the basic protein of myelin IgM in the blood of children with traumatic brain injury for a comprehensive assessment of the severity and prediction of outcomes of TBI. MATERIAL AND METHODS: 81 children with traumatic brain injury (TBI) of varying severity and 29 children of the comparison group aged 2 months to 18 years were examined, in whom the content of IgM antibodies in blood plasma was determined. RESULTS: In groups of children with different severity of TBI, the average content of IgM antibodies in the blood is higher than in children of the comparison group, and the values of IgM antibodies correlate with the severity of TBI. In children with moderate TBI, the average level of IgM antibodies in the blood is significantly higher than in children with mild TBI, and in children with severe TBI, the average level of IgM antibodies in the blood is significantly higher than in children with moderate TBI. A repeated study found a significant decrease in the average content of IgM antibodies in severe TBI in children without post-traumatic epilepsy compared to their average content in children with post-traumatic epilepsy. CONCLUSION: Normalization (elimination) of IgM antibodies in children in the late period of TBI is associated with a prognostically favorable course of the autoimmune process in the brain; its absence indicates a prolonged autoimmune process. After TBI, it is recommended to include in the examination of children an immunological study of the content of antibodies to the basic protein of myelin IgM in the blood, the indicators of which, in combination with other data, make it possible to predict the outcomes of TBI.

Magnetically sensitive nanocomplex enhances antitumor efficacy of dendritic cell-based immunotherapy.

BACKGROUND: One of the major factors restricting in vivo efficacy of dendritic cells (DCs) based immunotherapy is the inefficient migration of these cells to the lymphoid tissue, wherein DCs activate antigen-specific T cells. A fundamentally new approach for the possibility of enhancing the antitumor effects of DC-based immunotherapy may be the use of magnetically sensitive nanocomplexes to increase the target delivery of DCs to the lymph nodes of the recipient. AIM: To study the antitumor and immunomodulatory effects of the DC-nanovaccine with magnetosensitive properties and its influence on the immunosuppressive tumor microenvironment in mice with sarcoma 37. MATERIALS AND METHODS: The antitumor, antimetastatic and immunomodulatory effects of DCs loaded with magnetic nanocomplex under magnetic field (MF) control in mice with sarcoma 37 have been investigated. RESULTS: Combined therapy contributed to a significant reduction in tumor volume and weight compared to the control group of mice and mice that received the DC vaccine without MF. Therapy with magnetically sensitive DC nanovaccine with and without the addition of the MF was accompanied by a significant down-regulation of the level of FoxP3, transforming growth factor ß, interleukin (IL)-10 and vascular endothelial growth factors, mRNA expression in tumor tissues. A significant increase in interferon-γ and IL-4 mRNA expression was found in mice treated with the magnetically sensitive DC nanovaccine under MF control. CONCLUSION: A significant increase in the antitumor efficacy of the DC vaccine can be achieved using magnetosensitive nanocarriers of tumor antigens under MF control.

Drag reducing polymers attenuate adverse effects of ischemia-reperfusion upon resection of liver metastases modeled by MC38 mouse colon adenocarcinomama.

BACKGROUND: The resection of metastases within healthy parenchyma improves significantly the long-term outcome in metastatic colorectal cancer. Until now, the resection technique involves Pringle maneuver, which allows reducing blood loss during transsection of liver parenchyma. However, the classical Pringle maneuver has restrictions due to ischemia/reperfusion (I/R) effect, in particular increasing risk of tumor recurrence after liver surgery. AIM: To study the pathological impact of surgical intervention and I/R effect on healthy liver tissue in the experimental setting by evaluating the markers of redox-homeostasis and oxidatively induced mutage-nesis, and also to assess the current possibilities of their correction by application of drag-reducing polymers (DRPs). MATERIALS AND METHODS: MC38 mouse colon adenocarcinoma cells were transplanted intrahepatically to C57Bl/6 mice. The influence of warm ischemia on metastatic potential of MC38 cells, the speed of superoxide radicals (SR) generation and 8-hydroxydeoxyguanosine content were studied. RESULTS: In case of modeled liver metastases, the surgery initiates an increase in the rate of SR generation into the remaining liver tissue and, consequently, provokes its ischemic injury. The application of DRPs protects liver tissue under I/R conditions. CONCLUSIONS: The warm I/R can promotes metastatic lesions in the healthy part of the organ with underlying increase in the rate of SR generation and oxidatively induced damage of guanine in DNA. The hemorheological effects of DRPs ensure increase of microcirculatory perfusion and oxygenation of liver tissues with the reduction of the rate of SR generation and decrease of 8-hydroxydeoxyguanosine as a marker of oxidatively induced mutations in DNA of hepatocytes. The intraperitoneal administration of nanomolar doses of DRPs prevents the activation of the growth of dormant metastatic MC38 cells in the liver. Further experimental and clinical study of these substances will allow reducing the risks of activation of uncontrolled tumor growth in the liver due to the pathological effect of post-operative I/R.

Non-linear dynamics theory and malignant melanoma.

Chaos theory (nonlinear dynamics) defines cancer as a complex adaptive system in which each cyclic point corresponds to the bifurcation at which changes in signaling pathways emerge. Quantitative assessment of chaos in digital medical images such as electron microscopy, histology and cytology sections collected from patients with malignant cutaneous melanoma employed the following calculation parameters: the irregularity of external contours, internal heterogeneity based on brightness distribution of macromo-lecules, chromosomes, organelles, inclusion bodies, cells and tissues, kurtosis, entropy and the asymmetry coefficient. The present study undertook a nonlinear analysis of the chaotic hierarchy of malignant melanoma. However, considerably more studies will need to be carried out to determine the exact interrelationship between different levels of the hierarchy in the biological system. Multidisciplinary collaborations are therefore essential to find evidence to answer questions that remain open to researchers and oncologists.

Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles.

Tumour hypoxia leads to radio and chemotherapy resistance among cancer patients. The aim of this paper is to formulate a hypothesis on the heterogeneity of hypoxia in solid tumours. Tumour vasculature is known to be significantly variable. The great structural and functional abnormalities of tumour microcirculation cause spatial and temporal heterogeneity in its perfusion. Tumours have constantly been under the influence of pulsatile blood perfusion with variable pressure that initiates inhomogeneous erythrocyte deformation and following impact on oxygen disorder release from red blood cells into plasma within the blood vessel. Furthermore, stochastically released oxygen in tumour vessel, plasma and interstitial fluid may lead to heterogeneity of hypoxia. Under the influence of increased heterogeneity of hemodynamic force, the oxygen molecules dissolved in blood plasma are inclined to form nanobubbles (NBs) in tumour vessels. Considering the fact that tumour interstitial fluid pressure is increased compared to normal tissues, we assume that oxygen NBs may burst under the impact of shear stress. During the course of mechanochemical reaction, when a nanobubble (NB) bursts, both reactive oxygen species and ions form in various charged states. In consequence of a chain reaction, free radical oxygen molecules bind to proteins and lipids, thus reducing oxygen molecules in a chaotic manner within the tumour. The proposed hypothesis should be used as a methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on NB conglomerates with drugs in the tumour.

Mitochondria in Lewis lung carcinoma cells under the effect of magnetosensitive nanocomplex and radiofrequency hyperthermia.

Electron microscopic study of Lewis lung carcinoma cell mitochondria after intravenous injection of a magnetosensitive nanocomplex based on ferric oxide (Fe3O4) nanoparticles and doxorubicin followed by radiofrequency hyperthermia showed that a common increase of the electron density of the cytoplasm was paralleled by mitochondrial edema in comparison with organelles of animals receiving doxorubicin alone. These changes were accompanied by virtually total lysis of the cristae and sharp clarification of mitochondrial matrix, which was seen from appreciable increase in mitochondria image brightness. Morphometric analysis showed lesser perimeter, area, and mean radius of the tumor cell mitochondria in animals receiving the injection of magnetosensitive nanocomplex and exposed to radiofrequency hyperthermia in comparison with those injected with doxorubicin alone. Histograms of distribution of the perimeter, area, and mean radius of the mitochondria after combined exposure to the nanocomplex and hyperthermia showed bimodal asymmetrical distribution. Injection of the magnetosensitive nanocomplex followed by radiosensitive hyperthermia led to more significant impairment of the tumor cell mitochondrial ultrastructure than doxorubicin alone.

[About the impact of the dendritic cell autovaccine on the results of treatment of non-small-cell lung cancer patients].

In thoracic department of the National Cancer Institute studied the effectiveness of dendritic cell autovaccine in the postoperative period in non-small-cell lung cancer patients. The results, showing good tolerance dendritic cell autovaccine. Shows the formation of the expressed antigen immune response after repeated injections dendritic cell autovaccine, as manifested after 4 revaccination. Results of survival patients non-small-cell lung cancer who received postoperative dendritic cell autovaccines demonstrate the high efficiency of the method and its applicability with a minimum of side effects. Further study of survival of patients non-small-cell lung cancer who received immunotherapy treatment, monitoring of compliance with the best mode of repeated injections.

[Effect of doxorubicine and heterogenous electromagnetic and thermal fields on the nonlinear dynamics of carcinoma Guerin development].

While local hyperthermia application the intratumoral blood flow is enhancing, leading to oxygenation and vascular permeability for antitumoral medicines. The work objective was to investigate the dependence of the development kinetics in carcinoma Gereni (CG) from combined action of doxorubicin (DR) and the kind of thermal impact, a contact one--due to a contact delivery of heat from a water heater and without contact - due to the tumor electromagnetic irradiation (EMI) using heterogenous electromagnetic field (EMF). DR was injected to the animals in a mass concentration of 1,5 mg on 1 kg of their body mass. The DR injection, a contact heating and EMI were started on the 8th day after the tumor reinoculation and kept on conducting once a 2 days. The course had included 5 injections and/or 5 seances of a contact heating and/or EMF. The combined action of DR and EMI, using spatially heterogenous EMF of applicator in environment of physiological hyperthermia, have had influenced mostly the inhibition of a nonlinear dynamics in CG development. Antitumoral action of DR in the animals with CG was influenced by thermal and nonthermal effects, which were initiated by spatially heterogenous EMF. Nonlinear dynamics of a CG development in animals did not depend from horizontal direction of isolines of a spatially heterogenous EMF of inductive applicator towards the tumor and duration of the irradiation procedure (15 or 30 minutes) after DR injection. The data obtained were exploited in clinical practice for the inductothermy optimal regimes elaboration while conducting complex treatment of patients, suffering oncological diseases.

The effect of electromagnetic field and local inductive hyperthermia on nonlinear dynamics of the growth of transplanted animal tumors.

AIM: To examine the effects of electromagnetic field with amplified magnetic component and local inductive hyperthermia (IH) on nonlinear dynamics of the growth of animal tumors. MATERIALS AND METHODS: Guerin carcinoma, Lewis lung carcinoma, sarcoma 45, Walker 256 carcinosarcoma and Pliss lymphosarcoma were studied. The animal tumors were exposed inside of loop aerial, 3 cm in diameter locally for 30 min. Parameters of electromagnetic irradiation (EI): frequency 40 MHz, magnetic intensity 72 A/m, electric intensity 200 V/m and the output power 50 W. The temperature measured by immersion of thermocouple inside the center of the tumor didn't exceed 38.5-39.5 degrees C. Nonlinear dynamics of the growth of animal tumors was analyzed by autocatalytic equation. The heterogeneity of ultrasonic image of the tumor was analyzed by Moran spatial autocorrelation. RESULTS: The strongest inhibition effect under the influence of EI was in Pliss lymphosarcoma and sarcoma 45. The growth stimulation of animal tumors after EI was recorded in Walker 256 carcinosarcoma. The use of mild IH increased the blood flow in the tumor of Guerin carcinoma. CONCLUSION: These results are important for clinical application because they testify the necessity of optimization of schemes for local EI during anticancer neoadjuvant therapy with the use of drugs or magnetic nanoparticles. The use of mild IH as a basis for the monotherapy of malignant tumors is not expedient.

Mechanochemically activated doxorubicin nanoparticles in combination with 40 MHz frequency irradiation on A-549 lung carcinoma cells.

Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm2. The lethal dose LD50 values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37 degrees C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.

Effects of mechanochemically activated doxorubicin and 40 MHz frequency irradiation on human A-549 lung carcinoma cells.

AIM: To study in vitro influence of mechanochemically activated (MA) doxorubicin (DOXO) and electromagnetic irradiation (EMI) on human lung carcinoma A-549 cells. METHODS: Solid state DOXO was MA by input energy 20 W/g during 5 min. Tumor cells were exposed to 40 MHz EMI with power density 2 W/cm(2) at temperature 37 degrees C. RESULTS: Particles of MA DOXO have sizes 10 time smaller than officinal DOXO, high performance liquid chromatography analysis showed that parameters of officinal and MA DOXO were quantitatively equal. Mechanochemical activation initiated in the drug formation of free radicals with g = 2.005, g = 2.003 and g = 1.97. LD(50) values of MA DOXO were 5 times lower than that of officinal drug. Cell survival decreased in the following way after effects EMI --> officinal DOXO --> MA DOXO --> officinal DOXO + EMI --> MA DOXO + EMI. CONCLUSION: Treatment by MA DOXO and drug with EMI at 37 degrees C showed better targeting of drug in human lung carcinoma A-549 cells outcomes than officinal DOXO.

The device and algorithm for estimation of the mechanoemisson chaos in blood of patients with gastric cancer.

The mechanoemission (ME) of blood is developed as a result of mechanochemical activation of a sample which is layered onto chromatographic paper. This paper describes computer-controlled device, aimed for generation, detection and analysis of ME data in the blood of the persons investigated. The original algorithm for estimation of ME chaos in blood is developed. For gastric cancer patients an increase of ME chaos is observed in comparison with healthy individuals and patients with inflammation of gastric mucosa. The concept of deterministic chaos is biohierarchical for the host of a cancer patient. In the light of this we have calculated that spatial chaos for gastric cancer patients is also increased in the geometrical structure of tumor cells and magnetic resonance imaging of the stomach. The concept of deterministic chaos may find an application in the development of new multi-computer organizations for medical diagnostic equipment.

Initial theoretical framework and problem solving concerning the enigma of heredity.

The difference in formulation of the question of heredity on a different level of knowledge in Brno in the 1830s and after 1850 is discussed in this article. In order to solve the problem the most important source is foreshown in the new philosophy of plant physiology and in physics. Mendel was pleased to have met excellent teachers of both these fields. This explanation is an example of Mirko Grmek's thesis: 'l'histoire des sciences est le laboratoire de l'épistomologie'.

Scientific animal breeding in Moravia before and after the rediscovery of Mendel's theory.

Leading Moravian sheep breeders, who joined with university professors and other educated citizens to form a Sheep Breeders' Society in 1814, looked to science to provide a reliable basis for breeding. Their activities reached a climax in the 1830s, when they defined and focused on heredity as the central research goal. Among the members taking part was Abbot Cyrill F Napp, who in 1843 would accept Mendel into the monastery. The contributions of Abbot Napp to the sheep breeders' view of heredity are here described. After 1900, when Moravian animal breeding sought to embrace Mendelism, in competition with other theories, a major influence was exerted by Jaroslav Krízenecký (1896-1964). In 1963, Krízenecký accepted responsibility for establishing the Mendel Museum (Mendelianum) in Brno as a vehicle for historical research into the origin and essence of Mendel's discovery.

Mechanoluminescence: lymphocyte analysis after exposure to ionizing radiation.

Lymphocyte mechanoluminescence (ML) develops as a result of mechanochemical activation of cells. This paper describes devices (tribogenerators) and techniques for lymphocyte mechanoluminescence analysis. At different stages of the cellular cycle the ML of non-irradiated peripheral blood lymphocytes (PBL) showed characteristic differences. After (60)Co gamma -irradiation of PBL in vitro at 0.25 Gy and 1 Gy an alteration of ML was observed with a relationship between ML values of lymphocytes, and also of mitochondria (MT), and the dose of ionizing radiation used. By using bioluminescence techniques it was shown that gamma-irradiation reduces the amount of ATP synthesized by PBL in the stationary phase.

Essence and origin of Mendel's discovery.

In early 19th-century Moravia, breeders of animals and plants joined with other interested citizens in the Moravian and Silesian Agricultural Society to debate economic priorities. Several of the senior members had a profound influence upon breeding theory: J.K. Nestler, Professor of Natural History and Agriculture at the University of Olomouc, left a collection of influential writings. In the context of sheep breeding he defined 'inheritance capacity' (Vererbungsfähigkeit), 'hereditary history' (Vererbungsgeschichte) and 'developmental history' (Entwicklungsgeschichte). His linking of the last two terms, as two sides of the same coin, puts Mendel's use of the second one in context. Professor F. Diebl taught the same topics as Nestler at the Philosophical Institute in Brno, with a bias towards plants. Diebl's lectures were attended by Mendel who gained top marks in three examinations. Diebl stressed the importance of artificial pollination to produce new varieties and recognised peas and beans as suitable subjects for the procedure. Prelate Cyrill Napp, abbot before Mendel, had a deep interest in heredity and how it was transmitted through both sexes. He generously supported Mendel's research. A happy blend of economic and academic influences, together with original talent and inner drive, led to Mendel's great discovery.

Physical dosimetry and biological indicators of carcinogenic risk in a cohort of persons exposed to unhealthy ecological factors following the Chernobyl Nuclear Power Plant accident.

The April 1986 Chernobyl Nuclear Power Plant accident caused ecological changes in the Ovruch State forests in the Zhytomir oblast in the Ukraine. The highest radioactivity existed in moss, followed by the pine-forest substrate and soil. During 1984-1985, the pine needles were primarily surface contaminated, whereas during 1986-1988, they were contaminated secondarily. Radioactivity in air was highest (1.07+/-0.185 Bq/l) during dry and sunny weather and when trees were felled; the lowest levels (0.196+/-0.044 Bq/l) occurred during periods of stable snow coverage. Between 1987 and 1989 (i.e., after the Chernobyl accident), the caesium levels in forestry employees exceeded by 13.9-fold the average levels found in the Ukrainian Polessje population. Ovruch forest guards and woodcutters had the highest effective equivalent doses of radiation, and they therefore exhibited the highest carcinogenic risk.