Biodistribution of Detonation Synthesis Nanodiamonds in Mice after Intravenous Administration and Some Biochemical Changes in Blood Plasma.

Biodistribution of nanodiamonds in mice after intravenous administration, activities of AST and ALT, and the level of bilirubin in the blood plasma were studied in 2.5 h and 10, 35, and 97 days after injection of nanodiamonds. In 2.5 h after intravenous injection, nanodiamonds mainly accumulate in the lungs and liver. Then, redistribution of nanodiamonds from all organs to the liver was observed. Activities of AST and ALT and the level of bilirubin in the blood increased after 2.5 h and then decreased to the initial values.

Efficiency of Ampicillin-Associated Biogenic Ferrihydrite Nanoparticles in Combination with a Magnetic Field for Local Treatment of Burns.

We studied the effectiveness of using magnetic ferrihydrite nanoparticles of bacterial origin carrying ampicillin for local treatment of burn wounds in rats using a magnetic field. It was found that the use of these nanoparticles in combination with a magnetic field accelerated wound healing and reduced the titer of microorganisms in comparison with the corresponding parameters in the untreated animals and animals treated with nanoparticles or ampicillin alone.

Distribution of Ferrihydrite Nanoparticles in the Body and Possibility of Controlling Them in an Isolated Organ by a Permanent Magnetic Field.

We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.

The Spatial Metabolic Heterogeneity of Solid Type of Enrlich Carcinoma.

In this work, we investigated the NAD(P)-dependent dehydrogenase activity in different fields of the solid form of Ehrlich carcinoma. It was shown that there is a metabolic distinction between different fields of the solid tumor. In this way, there is a significant difference between the ascites and solid type of Ehrlich carcinoma. In the central area of the tested sample of tumor tissue, there is a high intensity of energetic metabolism and biosynthetic processes as opposed to the peripheral areas. Previously, we proposed the concept of nonspecific metabolic reaction of the cell in organism upon the influence of negative factors. In accordance with this concept, our results indicate the development of adaptation in the tumor cells in the central area of the tested sample.

The metabolic changes in tumor-associated macrophages during cancer grow in mice with Ehrlich ascites carcinoma.

In this work, we investigated the activity of the key NAD(P)-dependent dehydrogenases associated with macrophage tumors in mice with Ehrlich ascites carcinoma. It was shown that cancer grow is associated with the development of conditions in macrophages leading to a decrease in the substrate flow intensity in the tricarboxylic acid cycle, deceleration of oxidative deamination of L-glutamate, NADP regeneration, and a decrease in the antioxidant defense efficiency. There results are consistent with our recent concept on the nonspecific metabolic reaction of cells to extreme exposures.

Detection of nanodiamonds in biological samples by EPR spectrometry.

In model experiments in vitro, the applicability of the EPR spectrometry method for the detection of modified nanodiamonds (MNDs) in blood and homogenates of mouse organs has been established. A characteristic signal (g = 2.003, ΔH ≈ 10 G) is observed in the samples of biomaterials containing MNDs, the intensity of which increases linearly with the concentration of nanoparticles in the range of 1.6-200 µg MNDs per 1 mL of the sample. The EPR method in biomaterials reveals the presence of intrinsic paramagnetic centers, signals from which are superimposed on the signal from the MNDs. However, the intensity of these signals is small, which makes it possible to register the MNDs using EPR spectrometry with the necessary accuracy. The data obtained open up the prospects of using the EPR method for studies of the interorgan distribution, accumulation, and elimination of MNDs during their intravenous injection into experimental animals.

Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

Elimination of iron-containing magnetic nanoparticles from the site of injection in mice: a magnetic-resonance imaging study.

Suspension of magnetic nanoparticles (0.7 g/liter) obtained from Klebsiella oxytoca culture was injected intraperitoneally (1 ml), intramuscularly (in the hip; 100 µl), and subcutaneously (200 µl) or administered orally instead of drinking water for 2 days. The presence of magnetic nanoparticles was evaluated detected by MRI in 15 min and 2 h after injections and in 1 and 2 days after the beginning of oral consumption of the suspension. Magnetic nanoparticles were eliminated from the site of intramuscular and intraperitoneal injections and after oral consumption. The period of elimination after intramuscular and intraperitoneal injections did not exceed 2 h, while after oral consumption it corresponded to the time of gastrointestinal tract contents evacuation.

Metabolic changes in the liver of mice with Ehrlich ascites carcinoma.

The dynamics of NADP-dependent dehydrogenase activity and malonic dialdehyde content in the liver were studied in mice with Ehrlich ascites carcinoma. Tumor growth was accompanied by the development of conditions for an increase in the intensity of energy metabolism and amphibolic role of the tricarboxylic acid cycle in LPO activation in liver cells.

[Lymphocytes enzymatic status and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cancer]. / Osobennosti énzimaticheskogo statusa limfotsitov i kislorodzavisimogo metabolizma neitrofilov perifericheskoi krovi u bol'nykh rakom pochki.

The immune system, one of the most important homeostatic organism systems, is actively involved in the protection against malignant tumors. The earliest sighs of immune homeostasis disorders should be invetigated at the cellular level, because of cell functional manifestations depend on the state of intracellular metabolic reactions. The study of lymphocyte NAD(P)-dependent dehydrogenases activity and peripheral blood neutrophils oxygen-dependent metabolism in patients with renal cellular carcinoma (RCC) showed a decrease in the intensity of ribose-5-phosphate and NADH-dependent synthetic processes, inhibition of terminal reactions of glycolysis. Altered activities of the studied enzymes favor an increase in outflow of intermediates of the Krebs cycle on the reaction of amino acid metabolism in peripheral blood lymphocytes. Radical nephrectomy was accompanied by increased activity of glycolysis. The basal level chemiluminescent of peripheral neutrophils of RCC patients response was higher both before and after operations. Stimulation of neutrophils by opsonized zymosan in vitro leads to increase in oxidative metabolism activity, most in 14 days after surgery period. Before and 30 days after surgery, adaptive metabolic capabilities of neutrophilic granulocytes decreased.

[Metabolic changes of lymphocytes and neoplastic cells in mice with Ehrlich ascites carcinoma during tumor growth].

Changes in the activities of NAD+- and NADP-dependent dehydrogenases of lymphocytes and tumor cells were studied in mice with Ehrlich ascites carcinoma, as well as changes in the concentrations of oxaloacetate, lactate, and NAD+ in the course of tumor growth. During the major period of tumor growth, conditions are produced in the lymphocytes for increased intensity of aerobic reactions directed at energy reproduction combined with a somewhat decreased intensity of synthetic processes. In the tumor cells, conditions predominantly arise for intensification of plastic metabolic reactions and reactions related to anaerobic energy reproduction.

[Metabolic changes in rat liver in the recovery period after hyperthermic exposure]. / Issledovanie metabolicheskikh izmenenii pecheni krys v dinamike vosstanovitel'nogo perioda posle gipertermicheskogo vozdeistviia.

The metabolic changes in rat liver were studied during a reduction period after the overheating (25 min, 42 degrees C) using the isolated organ perfusion. First six hours after the treatment were characterised by a decrease of the respiration rate, the activation of glycolysis and an exhaustion of hepatic carbohydrate resources. The development of adaptive reaction resulted in the recovery of respiration rate to 18 h. This may provide subsequent restoration of hepatic metabolism and normalisation of the organ functioning.

Evaluation of antitumor activity of rubomycin deposited in absorbable polymeric microparticles.

An experimental dosage form of rubomycin is developed: the drug is incorporated in absorbable polymeric (polyhydroxybutyrate) matrix in the form of microparticles. Antitumor efficiency of this rubomycin dosage form was studied in laboratory mice with transplanted Ehrlich ascitic carcinoma. Rubomycin deposited in polymeric microparticles exhibited pronounced antitumor activity, inhibited the proliferative activity of Ehrlich ascitic carcinoma, and improved survival of mice with tumors. This dosage form of the drug can be used for local injections.

[Bioluminescent method for determination of concentration metabolic substrates and NAD+ in the lymphocytes].

We have developed a new bioluminescent method for determination of concentrations of pyruvate, lactate, malate, glutamate and NAD+ in the periferal blood lymphocytes from mice with Ehrlich ascites carcinoma. There were blood samples of intact mice for control. We found that variations of these substrates, depend on stage of malignant growth.

Role of S2 receptors in the stimulatory effect of serotonin on hemopoietic bone marrow stem cells.

Studies by the method of splenic exocolonies with serotonin receptor blockers methysergide and cyproheptadine showed that S2 receptors are involved in the stimulatory effect of serotonin on hemopoietic bone marrow stem cells.

Induction of blebbing in Ehrlich ascitic adenocarcinoma cells during in vitro hyperthermia.

We studied the effect of in vitro hyperthermia on induction of blebbing in cultured Ehrlich ascitic adenocarcinoma cells. Hyperthermia (42-48 degrees C) promotes induction of blebbing in cell culture, but this induction is reversible, and cessation of hyperthermia leads to almost complete recovery of the morphological composition of cell suspension.

Metabolism of lymphocytes in mice with Ehrlich ascites carcinoma.

The pattern of metabolic processes in lymphocytes of mice with Ehrlich ascites carcinoma depended on the stage of tumor growth.

Early effects of cis-dichlorodiammine platinum (II) on tumor progression and programmed death of Ehrlich ascites carcinoma cells.

We studied the effects of cis-dichlorodiammine platinum (II) on different pathways of cell death in cultured Ehrlich ascites carcinoma in vitro and on subsequent growth of transplanted tumor in vivo. One-hour incubation with the cytostatic modulated apoptosis in cell culture. However, exposure of cell culture to a minimal effective concentration of cis-platinum(II)diammine dichloride promoted the growth of transplanted tumor.

Metabolism in perfused rat lived at different terms after short-term hyperthermia.

The metabolic state of rat liver was studied in vivo 1, 6, and 18 h after single hyperthermia (42 degrees C). It was shown that intracellular compensatory reactions involved in restoration of the energy state and realization of endogenous cytoprotective mechanisms play a role during recovery.

Bioluminescent analysis of intensity of pathological oxidative processes in cells of perfused rat liver after hyperthermia.

We studied the possibility of evaluation of the intensity of pathological oxidative processes in rat liver using an integral bioluminescent test with controlled perfusion of the isolated organ. The test revealed a significant correlation between the level of TBA-reactive products and bioluminescence intensity.