Lithium-Modified Sorbent: Effects on Hemostatic Responses In Vitro.

The effects of a lithium-modified sorbent based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/Li) and a lithium-free sorbent (Al2O3@PDMS) on some indicators characterizing blood clotting under hemosorption conditions were compared in vitro. Sorbent Al2O3@PDMS/Li had significantly lower reactogenic effect on the blood passed through the column than the sorbent without lithium. This was seen from the degree of platelet reduction (66×109 vs 19×109/liter) as well as a less pronounced hypercoagulation shift in chronometric indicators. In contrast to lithium-free sorbent, Al2O3@PDMS/Li demonstrated the ability to reduce the concentration of fibrinogen. However, this had no impact on the density characteristics of the blood clot assessed by thromboelastometry such as maximum clot firmness, angle and fibrin clot formation time, amplitudes at 10 and 15 min after clotting time, which are known to depend on the quantity of platelets and the concentration of functionally active fibrinogen.

Effect of Melatonin on the Content of CD3low and CD3hi T Cells in the Thymus of Mice with Functional Pinealectomy.

Continuous lighting for 14 days (functional pinealectomy model) leads to a decrease in the relative number of CD3low and CD3hi T lymphocytes and the CD3low/CD3hi ratio in the thymus of C57BL/6 mice. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight, 14 days) against the background of functional pinealectomy restores the percentage of CD3low and CD3hi thymocytes and CD3low/CD3hi ratio to the control values. Hence, prolonged continuous illumination inhibits the differentiation and maturation of young thymocytes into mature forms, while melatonin treatment helps to compensate the effects of functional pinealectomy triggering cell proliferation in the thymus from the earliest stages of proliferation and differentiation of T cells. Thus, melatonin has immunotropic properties and can be used for correction of the consequences of functional pinealectomy.

New Carbon-Mineral Sorbent Based on Aluminum Oxide, Polydimethylsiloxane, and Single-Wall Carbon Nanotubes: Assessment of the Effect on Erythrocytes In Vitro.

A comparative study of the effect of a sorbent with nanotubes (Al2O3@ WCNT-PDMS) and a carbon-mineral sorbent (Al2O3@C) on the parameters of human erythrocytes was carried out. Using scanning flow cytometry, the morphological and functional parameters of venous blood erythrocytes as well as drainage blood after its perfusion through columns with sorbents were determined. The compared samples Al2O3@SWCNT-PDMS and Al2O3@C are similar by their effect on the morphological and functional parameters of erythrocytes. The maximum membrane extensibility increased to a greatest extent after contact with Al2O3@C, the amount of hemoglobin in erythrocytes decreased to the greatest extent after perfusion through a column with Al2O3@SWCNT-PDMS sorbent. The scanning flow cytometry is promising for assessing the effect on erythrocytes of new sorption materials intended for blood detoxification. Changes in the parameters of erythrocytes of blood collected in a sterile drainage system for subsequent reinfusion were revealed.

Effect of a New Lithium Preparation on the Behavior of CBA/CaLac Mice in an Experimental Conflict Model.

The use of lithium drugs in clinical practice requires constant monitoring of lithium plasma concentration, because toxicity is sometimes observed at therapeutic concentrations of lithium. This is often associated with fluctuations of plasma concentration of lithium ions after intake of individual doses. Therefore, the use of a porous carrier providing a stable blood level of the drug is extremely promising and important for clinical practice. We studied activity of a new lithium drug (lithium complex) consisting of aluminum-silicon base and lithium citrate immobilized on its surface. Lithium carbonate served as the reference drug. It was shown that lithium carbonate and lithium complex exhibited no anxiolytic activity in the conflict model, but produced an antidepressant effect and improved exploratory behavior of animals.

Cytotoxicity of Aluminum-Silica Matrices Modified with Carbon Nanotubes.

We studied the effect of aluminum-silicon matrices modified with carbon nanotubes on proliferation and production of nitric oxide by splenocytes, thymocytes, and bone marrow mononuclear cells of female db/db mice. Synthesized matrices decreased cell proliferation and suppressed NO production by the studied cells.

Effects of Melatonin on the Body Composition, Physical Performance, and Blood Erythrocyte Indexes of C57Bl/6J Mice Exposed to Continuous Illumination.

Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group. Studies by the low-field NMR spectrometry detected lower lean body mass, total body water, and especially, fat content (by ~13%) in animals receiving placebo. Melatonin treatment led to an increase in the lean body mass and total body water on day 7 (in comparison with the placebo group) without affecting fat mass. On day 14 of continuous illumination, lean body mass increased in comparison with the corresponding parameter in the control and placebo groups. Melatonin had no effect on the physical endurance of mice exposed to continuous illumination (assessed by the grid hanging test).

Effect of Lithium Preparations on Cerebral Electrophysiological Activity in Rats.

The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).

Melatonin-Aluminum Oxide-Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus.

We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.

Effects of Melatonin, Aluminum Oxide, and Polymethylsiloxane Complex on the Expression of LYVE-1 in the Liver of Mice with Obesity and Type 2 Diabetes Mellitus.

The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.

Morphological Criteria of Cell Differentiation Stages in Experimental Hepatocarcinoma and Evaluation of Antitumor Drug Efficiency.

Structural polymorphism of 5 cell differentiation stages of hepatocarcinoma-29 from ascitic fluid is detected and the morphological criteria for identification of these stages are defined on the base of optic and electron microscopy findings, cytofluorometry, and DNA cytometry. The percentage of cells at differentiation stages 4 and 5 in the tumor structure increases after hepatocarcinoma cell inoculation into the hip. Injection of a cell cycle-modulating substance to animals with tumor growth shifts the proportion of cells with various differentiation stages. The morphological criteria of 5 stages of hepatocarcinoma-29 cell differentiation can be used for prospective drug testing.

[Effects of lithium carbonate nanosized particles on oxidant-antioxidant status in tumor tissue of hepatocarcinoma-29].

Oxidant-antioxidant status in tumor tissue of male-mice CBA at spontaneous course of hepatocarcinoma-29 and after repeated injections of lithium carbonate nanosized particles was evaluated on changes of lipid peroxidation (LPO) products level reacted with 2-thiobarbituric acid (TBA) as indicator of oxidative stress and activity of superoxide dismutase (SOD) and catalase enzymes as indicators of antioxidant defense by spectrophotometer <> (Bio-Rad, USA). Tumor development after hepatocarcinoma-29 cells injection into muscle right leg changed the levels of LPO activity in two-phase manner. TBA-active products content were decreased in 2,4 times in comparison with the control indicates after invasion of tumor cells, it was raised in 2,1 times at excessive tumor growth and diminished at terminal stage. Catalase activity was significantly elevated, but SOD activity was reduced in tumor tissue samples at active growth of hepatocarcinoma. The repeated injections of lithium carbonate nanosized particles at hepatocarcinoma inhibited processes of lipid peroxidation in tumor tissue in 2,4 times, but didn't influence on activities of catalase and SOD. Thus the effects lithium carbonate nanosized particles injections referred on maintenance of balance between the oxidant and antioxidants may be of some help to limit the progression of precancerous condition toward malignancy and tumor growth.

Effects of Nanosized Lithium Carbonate Particles on the Functional Activity of Macrophages During Development of Hepatocarcinoma 29.

The functional activity of macrophages in response to injection of nanosized lithium carbonate particles after initiation of hepatocarcinoma 29 in male CBA mice was evaluated by the production of NO, arginase activity, and absorption of zymosan granules. In intact animals, NO production by peritoneal macrophages increased by 4 times and arginase activity 3.1 times in response to a single injection of nanosized particles into the hip muscle. The level of NO production by macrophages remained high after 4 and 5 injections, while arginase activity returned to normal. The level of phagocytic peritoneal macrophages increased by 1.4 times after 5 injections of the particles. The level of NO production by macrophages gradually increased in animals with hepatocarcinoma developing in the hip muscle: by 1.6 times on day 3, 3.2 times on day 7, and by 2.6 times on day 13 in comparison with the corresponding parameters in intact animals. The increase of NO production by peritoneal macrophages after tumor process initiation was not paralleled by changes in arginase activity and absorption of zymosan granules. The results indicated that injection of nanosized lithium carbonate particles after inoculation of hepatocarcinoma 29 cells in the right hip muscle tissue was inessential for the function of peritoneal macrophages by the studied parameters.

[Effects of lithium carbonate nanosized particles on nitric oxide production and arginase activity in tumor and peritoneal macrophages in hepatocellular carcinoma 29].

Three groups of male CBA mice were used. Group 1 consisted of intact mice. Hepatocarcinoma cells 29 (HCC-29) were transplanted into the right thigh muscle of animals group 2. Group 3 mice were injected 0.1 ml of lithium carbonate nanosized particles (NPs Li2CO3) at a dose of 0,058 mg on periphery of tumor growth one fold (3 day) and 5-fold (7 and 13 days). On day 7, numerical density of macrophages was raised in 5.8 times, the NO levels were increased by 1.9 times, and arginase activity was decreased in HCC tissue as compared with those values in normal liver. Tumor growth led to an increase in NO production by peritoneal macrophages (pMf) in 2.8 and 2.2-fold on day 7 and 13 days, respectively, and hadn't effect on arginase activity. A single injection of NPs Li2CO3 after inoculation tumor cells (3 days) didn't alter the NO levels rise in the tumor but five injections (7 days) increased it in 1.7 times as compared with values of mice group 2. The treatment of NPs Li2CO3 influenced the increasing the number density of macrophages in the tumor. Numerical density of macrophages in the tumor of mice group 3 was increased 9.6 and 1.6 times as compared with similar values in groups 1 and 2, respectively on 7 day after 5 injections of NPs Li2CO3. Treatment of NPs Li2CO3 after tumor cell transplantation didn't affect on the rise of NO levels and arginase activity in pMf. Thus, the effects of NPs Li2CO3, administered after HCC-29 cells transplantation, aimed at increasing activity of the NO-synthase way in HCC tumors and pMf, which can reduce the arginine levels required for tumor growth.

Effects of nanosized lithium carbonate particles on intact muscle tissue and tumor growth.

The effects of nanosized lithium carbonate particles on muscle tissue structure and development of experimental hepatocarcinoma-29 transplanted into the hip were studied in CBA mice. Necrotic changes in all structural components of the muscle were detected after intramuscular injection of nanosized lithium carbonate particles to intact animals. Regeneration of the muscle fibers after lithium carbonate treatment was associated with a significant increase in macrophage count, number of microvessels, activation of fibroblasts, and complete recovery of the organ structure. Injection of lithium carbonate nanoparticles at the periphery of tumor growth caused tumor cell necrosis, destruction of the vascular bed, and attraction of neutrophils and macrophages to the tumor focus. After the preparation was discontinued, the tumor developed with lesser number of vessels, smaller tumor cells, and lesser deformation of the cell nuclei structure.

Effect of Noolit, a novel lithium preparation, on electrophysiological activity of rat cerebral cortex.

The effects of lithium carbonate and Noolit, a novel lithium enterosorbent, on electrophysiological activity of cerebral cortex in rats were compared. Both agents potentiated the theta-, alpha-, and beta-rhythms and modified the response to rhythmic flash stimulation from potentiation to inhibition of cerebral rhythms. Moreover, these drugs increased dispersion of all rhythms. By contrast to lithium carbonate, the effect of Noolit was milder and developed more slowly.

Behavioral effects of novel enterosorbent Noolit on mice with mixed depression/anxiety-like state.

The aim of this work was to examine the behavioral effects of a novel lithium-based enterosorbent, Noolit (665 mg/kg), on male mice with mixed depression/anxiety-like state evoked by exposure to repeated social defeats in daily agonistic confrontations. The lithium component allows Noolit to be used as a psychotropic drug. Two experiments are described, in which the therapeutic and preventative effects of chronic Noolit treatment were examined. Response to Noolit was assessed in the plus maze, open field, partition test, and Porsolt's test. In both experiments, Noolit produced obvious anxiolytic and antidepressant effects. Treatment with Noolit fully restored some behavioral parameters in the plus maze and open field in depressed mice and prevented depression that would otherwise have developed. It has been suggested that enterosorbent Noolit can be a potent drug for the treatment of mixed anxiety/depression pathologies and for prevention of mood disorders.

Effect of enterosorbent noolith on behavior and serotonin (1A) receptors in mouse brain.

Protective properties of a new enterosorbent noolith (lithium ions immobilized on mineral matrix) were studied in C57Bl/6J mice predisposed to depression caused by intermale confrontations. The drug was administered daily for 15 days after the 5th confrontation and then the animals were tested in the forced swimming test. The number of specific(3)H-8-OH-DPAT binding sites in 3 brain regions was determined. It is shown that noolith produced an antidepressive effect manifested in decreased immobility time in the Porsolt test. Moreover, noolith reduced the number of 1A-serotonin receptors in the frontal cortex and hypothalamus. It is concluded that noolith possesses protective properties.

Physicochemical properties and applications of carbon-mineral sorbents.

Carbon-mineral sorbents successfully combine a high mechanical resistance of the mineral matrix and a high activity of carbons. It is possible to prepare a mineral matrix of the wanted structure and use it as the basis for producing carbon-mineral sorbents. SUMS-1 and SUMS-2 are the sorbents of mild action. In other words, they cause no thrombosis, they do not absorb oxygen and protein from blood, and they have almost no destructive effect on the blood cells. The sorbents are highly effective in adsorbing microorganisms and their toxins. Treatment of patients with different diseases (sepsis, meningitis, bronchial asthma, tuberculosis, pneumonia, thyrotoxicosis, pancreatitis, liver coma, different types of poisoning) with the SUMS-1 and SUMS-2 has given satisfactory results.