Experimental Study of the Efficacy of Sodium Deoxyribonucleate Used in Combination with Co-Transplantation of Mesenchymal and Hematopoietic Stem Cells after Exposure to γ-Radiation.

We studied the possibility of using sodium deoxyribonucleate (Derinat) for improving the efficiency of co-transplantation of mesenchymal (MSC) and hematopoietic stem cells (HSC) to female F1(CBA×C57BL/6) mice with bone marrow aplasia caused by exposure to γ-radiation. It was found that immunomodulator Derinat enhanced the effect of co-transplantation, in particular, triple post-irradiation administration of Derinat accelerated hematopoiesis recovery judging from the parameters of peripheral blood, total cellularity of the bone marrow and spleen, and animal survival. Single or double administration of Derinat prior to irradiation was ineffective. The optimal result was obtained when the following scheme was applied: MSC→HSC with an interval of 48 h starting during the first hours after irradiation and triple administration of Derinat (in 10-15 min, 3 and 7 days after irradiation) in a dose of 3 mg/mouse.

[Comparative effectiveness of ursodeoxycholic acid preparations in the treatment of biliary sludge].

In the clinical classification of cholelithiasis, biliary sludge (BS) is distinguished as the pre-stone stage. Ursodeoxycholic acid (UDCA) is a drug with an evidence base for effective and safe effects on BS. The therapeutic equivalence of various UDCA drugs remains an important issue for clinical practice. AIM: To conduct a comparative analysis of the effectiveness of the use of UDCA: Ursofalk with other UDCA drugs for the treatment of BS in a fixed dose of 10 mg/kg of body weight. MATERIAL AND METHODS: The observation group consisted of 225 patients with various types of BS. In randomized groups, the comparison of the effectiveness of UDCA drugs in the dissolution of BS was determined by the data of ultrasound of the gallbladder. Dynamic ultrasound cholecystography using a standardized technique was performed to study the effect of the compared drugs on the contractile function of the liver. When analyzing the impact of ursotherapy on the clinical manifestations of BS, the dynamics of biliary pain syndrome and dyspeptic disorders were evaluated. RESULTS: A comparative analysis of the effectiveness of UDCA drugs for BS lysis with a high degree of confidence established the advantage of Ursofalk: after 3 months in 80%, and after 6 months of therapy in 95.65% of patients, a regression of BS was detected. In the group of patients who took other UDCA, the corresponding indicators were 46.36% and 67.27%. The greatest effectiveness of ursotherapy was demonstrated in the BS variant by the type of suspension of hyperechogenic particles, the lowest in the variant by the type of putty-like bile in the form of mobile or fixed clots. In the last variant of BS, the relationship between the success of lysis with the extension of the UDCA intake period to 6 months and the preferred choice of Ursofalk was traced. Normalization of the contractile function of the gallbladder was noted in patients who took Ursofalk. CONCLUSION: From the standpoint of therapeutic effectiveness, the drug of choice for the treatment of BS, regardless of its type, is Ursofalk, which has proven the best dynamics of BS litolysis, recovery of the contractile function of the gastrointestinal tract, and relief of clinical symptoms.

Effect of Different Regimens of Co-Transplantation of Hemopoietic and Mesenchymal Hemopoietic Stem Cells on the Rates of Hemopoietic Recovery in Laboratory Mice Treated with Cyclophosphamide in Sublethal Doses.

We studied the effect of mesenchymal stem cells and hemopoietic stem cells co-transplanted in different regimens (sequence and intervals between the injections within 0-48 h) on the rate of the bone marrow hemopoiesis recovery in 468 inbred mice with cytostatic aplasia caused by a single injection of cyclophosphamide in a dose of 500 mg/kg. The efficacy of stem cells was evaluated by animal survival and general physical condition, body weight dynamics, peripheral blood counts (leucocytes, platelets, and reticulocytes), total cellularity and the presence of hemopoietic stem cells in the bone marrow on day 9 after cyclophosphamide injection. The relative content of hemopoietic stem cells in the total myelokaryocyte pool was assessed by flow cytofluorometry using specific monoclonal antibodies to CD117 and CD184. The stimulating effect of co-transplantation of mesenchymal stem cells and hemopoietic stem cells on hemopoiesis was demonstrated by the indices of total cellularity and the relative content of CD117+ hemopoietic stem cells. The schemes with injection of mesenchymal stem cells 24-48 h prior to injection of hemopoietic stem cells were most effective.

[Ischemic stroke in young age].

We studied 203 patients (116 male, 87 female, mean age 34,6±8,2 years) with ischemic stroke (IS). The study was carried out in one week - 14 months after the development of stroke. All patients underwent MRT/CT of the brain, cerebral angiography (MRA, rarely - CTA or conventional angiography), duplex ultrasound and echocardiography. Antiphospholipid antibodies, homocysteine, platelet aggregation, blood clotting, methylenetetrahydrofolate reductase, prothrombin and factor V Leiden gene mutations were also studied along with routine clinical and biochemical blood tests. When it was indicated, antinuclear antibodies, DNA antibodies, antibodies to some viruses were studied and muscle biopsy was performed. The causes of IS were as follows: cerebral artery dissections (25%), cardioembolism (12%), antiphospholipid syndrome (11%), coagulography (7%), arterial hypertension (8%), atherosclerosis (3%), mitochondrial cytopathy (3%), cerebral vasculitis (1%), Moya-moya disease (0,5%), cerebral artery spasm after the aneurysm disruption (0,5%). The cause of IS remained unknown (cryptogenic stroke) in 29%. In a half of these cases, clinical presentations suggest the cerebral artery dissection as a cause of IS. However in the acute period the diagnosis was not verified by angiography which was conducted only in the late stage of stroke (3 months or more after stroke development).

[Internal carotid artery dissection: localization of cerebral infarcts and mechanism of their development].

To clarify the mechanism of the development of cerebral infarcts in the internal carotid artery (ICA) dissection, the data of neuroimaging (localization of infarcts) and angiography have been analyzed in 49 patients (19 females 30 males, mean age 35,6 +/- 11,3 years). Four variants of infarct localization have been distinguished: 1 - the whole ICA territory (middle and anterior cerebral arteries - MCA, ACA) - 10%, 2 - the territory of superficial and deep branches of MCA- 37%, 3- the territory of superficial MCA branches and cortical-medullar arteries - 31% (the cortex and underlying white matter - 19%, the periventricular white matter and semiovale center - 6%, combined localization - 6%); 4 - the territory of deep (perforating) MCA branches (the basal ganglia and adjacent white matter) - 22%. In most of patients (92%) the dissection resulted in the occlusion or severe stenosis of intracranial ICA which in a half of cases extended to MCA and/or ACA. In 72% patients dissection involved the extracranial ICA. The marked obstructive process in the dissected ICA allows to assume that the hemodynamic, but not embolic, mechanism plays a key role in the development of infarcts. This is in line with the frequent infarct localization in the end or border zones (superficial and deep) of brain blood supply (31%) and the development of stroke during a sleep (49%). Arterio-arterial embolism as a mechanism of ischemic stroke development was found in 8% of patients with the isolated extracranial ICA dissection. It caused stenosis of the lumenand in 6% accompanied by the pseudoaneurism formation. Thrombi formed inside the aneurism could be the origin of the embolism.

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

[Clinical efficacy of antihypertensive therapy of pregnant women with arterial hypertension with long acting nifedipine and bisoprolol].

Study aim was assessment of clinical efficacy of mono therapy with nifedipine SR/GITS and combination of nifedipine SR/GITS and bisoprolol as well as investigation of functional state of sympathoadrenal system (SAS) in pregnant women with arterial hypertension. Examination and treatment with nifedipine SR/GITS 30 mg/day and bisoprolol 2,5 - 5 mg/day was carried out in 21 patients with stage II hypertensive disease (HD) during trimester II of pregnancy. Initially all women including 20 practically healthy pregnant women (control group) had elevation of functional activity of SAS what was determined by high values of b-adrenoception of membranes of erythrocytes. In patients with stage II HD this parameter significantly exceeded that of control group. Administration of antihypertensive drugs for 3 weeks promoted significant lowering of all parameters of 24 hour blood pressure monitoring down to optimal level, lessening of pathological types of 24 hour blood pressure profile and lowering of functional activity of SAS.

[Psychophysiological development of two generations of female rats chronically exposed to gamma-irradiation during pregnancy in the total dose of 1 Gy and its modification by melanin].

The purpose of the work was to study the embryotoxic action of chronic gamma-irradiation of pregnant female rats (F0) during the first 10 days of pregnancy in the total dose of 1 Gy (mean dose rate of 5.31 mGy/hour) on psychophysiological development of posterity of the first (F1) and the second (F2) generations and its modification by natural pigment melanin (peroral 10 mg/kg once per day during the irradiation). 54 pregnant female Wistar rats were the objects of research were their 180 descendants of the first generation and about 400 descendants of the second generation of maternal and of paternal lines. Psychophysiological development and its correction by melanin estimated on ability to learning with the test of training a conditioned avoidance reflex in the shuttle box. Precise negative action of gamma-irradiation in the aforesaid dose on psychophysiological development of posterity of the first generation is established. At rats of the second generation the inferiority is shown mainly at descendants of maternal line. Application of melanin of natural origin in most cases diminished negative consequences of the irradiation.

[Experimental study of the neuroprotective properties of the melanin in embryos irradiated during antenatal development].

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats of line Wistar on a background continuous irradiations (dose rate of 2.6 mGy/h within 20 days of pregnancy) eliminated deficiency cognitive functions at posterity. On the basis of the received data it is concluded presence radioembryoprotective actions of melanin in the relation neuro embryotoxic effects of small dozes ionizing radiation. Taking into account small toxicity of melanin, the preparation can be perspective for practical application.

Evaluation of psychoemotional status of rats after brain injury and systemic transplantation of mesenchymal stem cells.

We studied the effects of systemic transplantation of mesenchymal stem cells obtained after culturing of autologous bone marrow on psychophysiological status of Wistar rats after diffuse brain trauma. Two months after systemic injection of mesenchymal stem cells we observed a decrease in manifestations of emotional behavioral reactions (anxiety and excitability) and shortening of the time of realization of drinking behavior in a T-maze. A significant positive effect of systemic transfusion of mesenchymal stem cells on avoidance conditioning in a shuttle box was observed 3 months after brain injury.

[The influence of the exogenous melanin on the development of the second generation of the female Wistar rats exposed during the critical period of the pegnancy at the nonsterilizing doses of different rate means].

The purpose of this study was to estimate the radio-protective activity of melanin for the reproductive status of Wistar rats. Wistar rats were exposed in utero either to the single gamma-irradiation on the tenth day of embryogenesis with the dose of 1 Gy or to the chronic gamma-irradiation with the total dose of 1 Gy during the first 10 days of embryogenesis. Such things like the ability of the rats to conceive, the embryogeny and early postnatal ontogeny of rat's posterity were studied. These doses of the radiation and the melanin did not produce the significant damages of the reproductive function of the survival offsprings of the first generation. The possible mechanisms of radio-protective effect of melanin on reproductive system of animals which have been exposed with the nonsterilizing doses at different mean dose rate were discussed.

[The effect of pulsed cyclical microware radiation on the conditioned behavior of rats]. / Vliianie tsiklicheskogo impul'snogo mikrovolnovogo oblucheniia na uslovno-reflektornuiu deiatel'nost' krys.

Research has been carried out to investigate the effects of pulsed cyclical microware exposure (7 GHz, 400 pps, 100 mcs, 10-20 mW/cm2, 10 or 20 cycles of "5 min exposure--4 min pause") on avoidance learning of rats. It was shown that reductions in conditioned behavior after cyclical pulsed microware exposure occurred at an SAR of 2.1 W/kg (10 mW/cm2). It was found the cumulation of the effects of the cycles at prolonged cyclical microwave exposures.

[Radiation-induced and embryotoxic effects in experimental hyperthyroidism]. / Eksperimental'no indutsirovannyi gipertireoz: ego radioembriotoksicheskoe deistvie.

The purpose of this article was investigation the development of the posterity rat (line Wistar) in the postnatal ontogenesis after combined and separate action of gamma-radiation (1.25 Gy at 20 days) and hyperthyroidism, provoked by toxic thyroid doses of 100 mg thyroidin per rat. It was shown that hyperthyroidism did not affect physical development of the irradiated posterity, but in a long-time period (7 month) it was revealed a decrease in ability to the training of posterity rats after the combined action of the factors.

[The influence of exogenous melanin on the development of female Wistar rats' posterity of first generation exposed to low doses at different dose rates during embryogenesis]. / Vliianie ékzogennogo melanina na razvitie potomstva pervogo pokoleniia krys Wistar, obluchennogo v émbriogeneze v maloi doze raznoi moshchnosti.

To research a radio-protective effect of melanin on the reproductive system during its creation the development of first generation posterity (900 descendants) of 125 pubertal female Wistar rats was examined after the single gamma-irradiation with a dose of 1 Gy (mean dose rate of 0.03 mGy/h), which they have been exposed to on the day ten of pregnancy, and the chronic gamma-irradiation with a total dose of 1 Gy (mean dose rate of 5.31 mGy/h) which they have been being exposed to during the first 10 days of pregnancy. The melanin of natural animal origin has the anti-radial effectiveness with the single irradiation increasing the number of alive newborn descendants in a litter and doubling their survival during the first 30 days after the birth. The melanin's effect is less expressed with the chronic irradiation.

[Comparative estimation of the effects of continuous and intermittent cyclical microwave radiation on the behavior of rats in the extraordinary situation]. / Sravnitel'naia otsenka vliianiia mikrovolnogo izlucheniia teplovoi intensivnosti v nepreryvnom i tsiklicheskom rezhimakh na povedenie krys v ékstremal'noi situatsii.

Research has been carried out to investigate the effects of pulsed microwave exposure without pause (7 GHz, 400 pps, 100 microseconds, 70-150 mW/cm2, exposure 10 min) and pulsed interrupted cyclical microwave exposure (5 min exposure--4 min pause--5 min exposure) on learned behaviors of rats in the paradigm of extraordinary situation (the rescue of the life). It was shown that reductions in conditioned behavior after acute pulsed microwave exposure occurred at SAR of 21 W/kg (100 mW/cm2) and after cyclical pulsed microwave exposure at SAR of 28.4 W/kg (135 mW/cm2).

[Experimental assessment of adaptive possibilities after chronic prenatal exposure to gamma irradiation at various absorbed doses]. / Eksperimental'naia otsenka adaptivnykh vozmozhnostei organizma posle antenatal'nogo khronicheskogo deistviia gamma-izlucheniia v raznykh pogloshchennykh dozakh.

The purpose of the investigation is the study of dose-response relationship at the antenatal exposure of low level ionizing radiation (137Cs, 1.0-1.25; 1.7-1.9 and 2.3-2.5 Gy during 20 days). The decrease of body weight in pregnant females and antenatal embryonic mortality at the doses 2.3-2.5 Gy are revealed. Physical postnatal anomalies with decrease of the adaptation were estimated by the strength endurance after antenatal exposure of gamma-rays at the doses of 1.0-2.5 Gy.

[Conditioned reflex activity in rats after chronic antenatal gamma irradiation in association with mercazolyl]. / Uslovno-reflektornaia deiatel'nost' krys posle khronicheskogo antenatal'nogo gamma-oblucheniia v sochetanii s merkazolilom.

The purpose of investigation is the study of combined influence of gamma-radiation (137Cs, 1.25 Gy during 20 days) and mercazolyl (20 mg/100 ml drinkable water) in utero on the intellectual state of rats in the postnatal ontogenesis. It was shown, that antenatal separate influence both of gamma-radiation and mercazolyl induced the delay of intellectual development in 2 and 7 months age. The combined influence of these factors induced essential increase observed effect. There is a party of the conditioned reflex activity in 7 month age.

[Treatment of mitral valve stenosis in pregnant women by the method of balloon valvuloplasty]. / Lechenie mitral'nogo stenoza u beremennykh sposobom kateternoi ballonnoi val'vuloplastiki.

Catheter-balloon mitral valvuloplasty was performed in 7 females with rheumatic mitral stenosis on the 19th-32nd week of pregnancy. Four patients were operated on with signs of cardiac insufficiency, two--in a state of pulmonary pre-edema. Edema of the lungs in one patient continued developing on the operating table. The results of the treatment were good in all cases. The area of the mitral orifice increased from 0.9-1.75 to 2.4-3.5 cm2. The pressure gradient between the left atrium and the left ventricle dropped from 25-40 to 2-8 mm Hg. This was attended by the disappearance of the diastolic murmur and the clinical manifestations of stasis in pulmonary circulation in all patients. The development of mitral regurgitation after the operation was not encountered in any of the patients. The period of roentgenoscopy lasted 17.5 min. on the average. Screens were used to protect the fetus from the direct effect of the X-rays. Pregnancy ended in delivery in 6 patients; spontaneous labor at term occurred in 4, cesarean section had to be performed in one patient with placenta previa; one woman gave birth to twins on the 36th week of pregnancy. All the babies were healthy. Catheter-balloon valvulotomy does not yield to closed mitral commissurotomy in efficacy. The fact that it is only mildly injurious and does not need general anesthesia make this intervention preferable for pregnant women suffering from mitral stenosis.