[Allogeneic umbilical cord blood cell therapy for children with autism: safety and efficacy of the method]. / Primenenie kontsentrata yadrosoderzhashchikh kletok pupovinnoi krovi u detei s autizmom: bezopasnost' i effektivnost' metoda.

OBJECTIVE: To evaluate effectiveness and safety of umbilical cord blood cells (UCBC) in children with ASD. MATERIAL AND METHODS: The study comprised 13 boys and 2 girls, mean age 7.0±0.5 years (test group), and 9 boys and 1 girl, mean age 6.0±1.3 years (control group) diagnosed with autism or autistic syndrome. UCBC were infused intravenously in a single dose of 250±20 million cells, four times at 14±3-day intervals. Dynamics of cognitive functions were assessed with WISC subscales, questionnaire Skvortsov Developmental Profile Survey and brainstem auditory evoked potentials (BAEPs) conducted before therapy and six months after the first injection. The dynamic of autistic symptoms was explored with CASD and ATEC questionnaires, fulfilled at the start of the study, 3 and 6 months later (test group) or at the start of the study, and 6 months later (control group). RESULTS: UCBC was well tolerated and caused no appreciable adverse effects. Observation revealed improvement in cognitive functioning and alleviation of autistic symptoms in patients of the test group six months after the first UCBC injection. Positive dynamics were more noticeable in the test group than in the control group receiving standard therapy. CONCLUSION: The use of UCBC is safe and might be effective in the complex therapy of autism.

Comparison of Biological Effects of γ-Radiation of Low and Ultra-High Dose Rate on Lymphocytes and Cultured Human Malignant Lymphoma Cells.

We studied the effect of low and high-dose rate photon radiation on activation of cell death by apoptosis and necrosis in malignant cell lines of lymphocytic origin Raji and Jurkat (human B and T-cell lymphomas) and normal human lymphocytes from healthy volunteers. It was shown that photon radiation with ultra-high dose rate induced significantly higher levels of "early" apoptosis and lower levels of necrosis compared to γ-radiation with dose rate used for radiation therapy.

Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats.

Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues.

[The effect of combination of glycyrrhizic acid with alpha-glutamyl-tryptophan on the experimental adenoviral infection].

In this work, the activity of glycyrrhizic acid (GL) and dipeptide alpha-glutamyl-tryptophane (EW) as single preparations or in combination (GL+EW) against experimental adenoviral infection in the syrian hamsters was studied. Application of gl and GL+EW was shown to decrease the level of the adenovirus replication in liver tissue by 0.6 - 1.2 lgTCID50 depending on the composition and time point of the post infection. It was also demonstrated that normalization of the structure of the liver tissue was required, which was shown on the level of both optical and electron microscopy. The results obtained in this work suggest that gl and GL+EW may be considered as potential component of the complex therapy of adenoviral infection.

[SEROTONERGIC REGULATION OF THE DUODENUM CONTRACTIONS].

The review contains an analysis of literature data on enhancement mechanisms of duodenum contractions arising during stimulation of the sympathetic trunk in the right thoracic cavity in dogs. It is established in experiments that There are mostly enhancement, not relaxation of the organ contraction occured. In this case the stimulatory effect due to the excitation of the parasympathetic fibers is excluded. The trimeperedin inhibit the serotonin receptors of autonomic ganglia neurons stimulatory activity during the nerve stimulation. It is concluded that the sympathetic trunk contain the preganglionic serotonergic nerve fibers, whose activation leads to increased bowel contractions. Direct adipinate-serotonin administration increased the bowel contraction that confirm the preganglionic serotonergic nerve fibers presence in the sympathetic trunk. The practical significance of these studies is that the new approach to the development of pharmacological agents to stimulate the motility of the gastrointestinal tract was found. The trimeperedin may inhibit the serotoninergic nerves activity that resulted in the perioperative constipation in surgical patients. Practical recommendation to exclude trimeperedin in preparing the patient for surgery to prevent perioperative constipation is formulated.

Efficiency of transplantation of human placental/umbilical blood cells to rats with severe spinal cord injury.

The effects of a single intravenous injection of human umbilical blood were studied on the model of severe spinal cord contusion injury in rats. Rats receiving no umbilical blood (spontaneous recovery) served as the control. All rats exhibited pronounced hind limb paraplegia and autonomic dysfunction of pelvic organs after the injury. Recovery of the hind limb function was evaluated by loading tests and locomotor activity testing in the open field using BBB score for open-field testing. Testing was carried out weekly for 8 weeks after the injury. Open-field testing showed a significant (p < 0.05) increase of the rate and volume of the hind limb motor activity recovery in the groups receiving umbilical blood infusions.

[Primary and secondary resistance to nicotine replacement therapy in tobacco dependent patients].

The terms of primary and secondary resistance to nicotine replacement therapy in tobacco dependent patients are defined. It is shown that treatment resistance is a result of a constellation of special clinical features of tobacco dependence, tolerance to nicotine, personality traits of the patients, family history of smoking, comorbid affective disorders and somatic diseases.

Effect of calcium phosphate materials on multipotent mesenchymal cells from exfoliated deciduous teeth (SHED cells) in vitro.

Various calcium phosphate ceramic materials were created and their effect on cultured mesenchymal cells from exfoliated deciduous tooth pulp was evaluated. Tricalcium phosphate ceramics provides best cell survival and is an optimal material for bone tissue engineering. Analysis of the effects of tricalcium phosphate ceramics on osteogenic differentiation of SHED cells suggests that this material potentiated dexamethasone-induced osteogenic differentiation, which manifested in the increased number of ossification foci and enhanced extracellular matrix production by cells. Thus, the tricalcium phosphate ceramics created by us is a promising biomedical material that can be used for tissue-engineered bone analogs.

In vitro studies of changes in human endothelial cell functions under the effect of imiquimod.

Imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) is an active immunomodulator with antiviral effects. In addition to its stimulatory effect on cell-mediated immunity, in vivo studies have detected its antiviral and antiangiogenic effects. Possible direct effect of imiquimod on endothelial cells remains not studied. We have shown that imiquimod inhibited proliferation and migration of human endothelial cells (EA.hy 926 strain) in vitro and induced apoptosis (but not necrosis) of endothelial cells and production of IL-6 cytokine. These results suggest that imiquimod inhibits angiogenesis via direct modulation of endothelial cell function.

[Application thymogen for preoperative preparation of elderly patients with tumor processes in abdominal cavity].

A double-blind, randomized, placebo-controlled study of the efficacy of Thymogen preparation for elderly patients for surgery on the solid tumors in abdominal cavity and retroperitoneal space was carried out. The drug has been administered by intranasal instillation of 100 mg once a day for 7 days before surgery. The isotonic sodium chloride solution for the placebo group in the same scheme was used. The preoperative use of Thymogen proved to be useful to restore the structural and functional parameters of cellular immunity. Immunomodulatory therapy resulted in the significant decrease in the number and range of post-operative complications and the shorting of the postoperative period.

[Disfunction of membrane-receptor system of blood cells in children with diabetes mellitus of type I and II].

When metabolic failure in children and adolescents with diabetes, are violations of the structural and functional properties of membrane - the receptor apparatus of cells, accompanied by a decrease in ATP levels, inhibition of activity of membrane-bound enzyme Na+, K(+)-ATPase, a sharp decrease in insulin binding receptor activity and decrease glucose uptake by cells that indicates a decline in cell sensitivity to insulin. Diabetes in children and adolescents occurs with lipid disorders, activation of the processes of lipid peroxidation, manifested increasing concentrations of both primary and secondary products of lipid peroxidation, changes in structural and functional properties of erythrocyte membranes, as well as disturbances in the antioxidant defense system. Changes in the studied indexes depend on the type of diabetes and duration of the disease. Imbalance in the system LPO-AOD in the background shows the development of dyslipidemia, oxidative stress, particularly pronounced in type 2 diabetes.

[Microbiological corrosion of aluminum alloys].

Biological corrosion of ADO quality aluminum and aluminum-based construction materials (alloys V65, D16, and D16T) was studied. Thirteen microscopic fungus species and six bacterial species proved to be able to attack aluminum and its alloys. It was found that biocorrosion of metals by microscopic fungi and bacteria was mediated by certain exometabolites. Experiments on biocorrosion of the materials by the microscopic fungus Alternaria alternata, the most active biodegrader, demonstrated that the micromycete attack started with the appearance of exudate with pH 8-9 on end faces of the samples.

[A new concept of development of neointimal hyperplasia]. / Novaia kontseptsiia razvitiia giperplazii intimy sosudov.

The intima hyperplasia is a major morphological feature of various arterial pathologies such as atherosclerosis, postangioplasty restenosis and transplantation arteriopathy. It is commonly assumed that smooth muscle cells (SMC) comprising loci of the intima hyperplasia originate from arterial media. However, recent studies suggest that the bone marrow could also supply circulating vascular progenitor of SMCs and endothelial cells (EC). Such bone marrow progenitors participate in the formation of a cellular mass of neointima after experimental allotransplantation, mechanical vessel injury or hyperlipidemia induced experimental atherosclerosis. Circulating SMC and EC progenitors are also likely to be involved in the transplantation arteriopathy development in humans but their roles in the atherosclerosis and restenosis remain to be determined. Stages of the mobilization, defferentiation and proliferation of SMC progenitors could provide point of attack for new therapeutic strategies for the treatment of proliferative vascular diseases. The precise understanding of the neointima cells origin could provide a key for development of the optimal therapeutic strategy of treatnent of such disorders. This review is focused on the pathological significance of circulating progenitors of the bone marrow origin, particularly on the SMC progenitors, for development of vascular wall disorders.

[Stenting of left common carotid artery kinking in the region of carotid subclavian anastomosis in a patient operated for occlusion of left subclavian artery]. / Stentirovanie peregiba levoi obshchei sonnoi arterii v oblasti karotidno-podkliuchichnogo anastomoza u bol'noi, operirovannoi po povodu okkliuzii levoi podkliuchichnoi arterii.

The paper presents a case report of left common carotid artery kinking treated by stenting in a patient with aortoarteritis. The kink had developed 10 months after performance of carotid-subclavian anastomosis for occlusion of left subclavian artery and steal syndrome. The stenting procedure of left common carotid artery is described. Follow-up for 42 months and control angiography 6 months after stent implantation demonstrated good outcome and regression of neurological symptoms. Special features of stenting procedure in coiled artery with unaltered walls are analysed. The authors mention that carotid stenting in this patient was the most appropriate method of surgical treatment. It is the first description of stent use for carotid artery kinking correction.

[Probable mechanisms of the regulation in the jejunum motility]. / Vozmozhnye mekhanizmy reguliatsii pishchevoi motoriki toshchei kishki.

It is a well-known fact that serotonin has a stimulative action on the motor-secretory activity of the gastrointestinal tract. Activation of 5HT3,4-receptors regulates neuronal responses of this action; it is possible to regulate efferent reactions by activating 5HT1,2-receptors (1, 2, 3). Carcinoid cells containing 5HT have 5HT3 and 5HT4 receptors on their superficial membranes. The object of this research was to determine the possible participation of serotonergic structures in the regulation of the jejunum motility.

[Permeabilization of tumor cells induced by pulsed electric fields in vitro]. / Permeabilizatsiia opukholevykh kletok in vitro pod deistviem impul'snykh élektricheskikh polei.

The permeabilization of tumor cells in vitro under the action of pulsed electric fields with a duration of 6 mks in the range of amplitudes 1-7 kV/cm was studied. In the mode of excitation in the ambience of localized plasma discharge in a chamber of special design, an enhanced damage to cells in suspension was observed. It is assumed that the enhancement is due to the synchronous action of the electric field and acoustic shock wave pulses. In the mode without the plasma breakdown of ambience, when the pulse duration of electric field of intensity of 1-2 kV/cm was increased to 60 mks, the efficiency of permeabilization increases nearly by one order. The experimental results are compared with the known theoretical models of cell membrane electroporation.

[Adrenocortical tumors with neuroendocrine differentiation]. / Adrenokortikal'nye opukholi s neiroéndokrinnoi differentsirovkoi.

18 adrenocortical tumours and 5 pheochromocytomas were studied immunohistochemically. Expression of synaptophysin and chromogranin A was found in cells of cortical adenomas, "frontier" neoplasms and in 20-75% of carcinoma cells, this ultramicroscopically was confirmed by observation of typical neuroendocrine granules. Some groups of cells of cortico-medullary tumours also expressed proteins of neural differentiation (protein S-100).

Itt1p, a novel protein inhibiting translation termination in Saccharomyces cerevisiae.

BACKGROUND: Termination of translation in eukaryotes is controlled by two interacting polypeptide chain release factors, eRFl and eRF3. eRFl recognizes nonsense codons UAA, UAG and UGA, while eRF3 stimulates polypeptide release from the ribosome in a GTP- and eRFl - dependent manner. Recent studies has shown that proteins interacting with these release factors can modulate the efficiency of nonsense codon readthrough. RESULTS: We have isolated a nonessential yeast gene, which causes suppression of nonsense mutations, being in a multicopy state. This gene encodes a protein designated Itt1p, possessing a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of Itt1p decreases the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons. Itt1p interacts in vitro with both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the nonsense suppressor effect of overexpressed Itt1p. CONCLUSIONS: The data obtained demonstrate that Itt1p can modulate the efficiency of translation termination in yeast. This protein possesses a zinc finger domain characteristic of the TRIAD proteins of higher eukaryotes, and this is a first observation of such protein being involved in translation.