Localized Increased Permeability of Blood-Brain Barrier for Antibody Conjugates in the Cuprizone Model of Demyelination.

The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood-brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability.

Distribution and Migration of Human Placental Mesenchymal Stromal Cells in the Brain of Healthy Rats after Stereotaxic or Intra-Arterial Transplantation.

Human placenta mesenchymal stromal cells were injected to healthy rats either stereotaxically into the striatum or intra-arterially through the internal carotid artery. Some cells injected into the brain migrated along the corpus callosum both medially and laterally or concentrated around small blood vessels. A small fraction of MSC injected intra-arterially adhered to the endothelium and stayed inside blood vessels for up to 48 hours mostly in the basin of the middle cerebral artery.

Methods of Generation of Induced Pluripotent Stem Cells and Their Application for the Therapy of Central Nervous System Diseases.

The use of induced pluripotent stem cells (IPSC) is a promising approach to the therapy of CNS diseases. The undeniable advantage of IPSC technology is the possibility of obtaining practically all types of somatic cells for autologous transplantation bypassing bioethical problems. The review presents integrative and non-integrative methods for obtaining IPSC and the ways of their in vitro and in vivo application for the study and treatment of neurological diseases.

Comparative Analysis of the Effects of Intravenous Administration of Placental Mesenchymal Stromal Cells and Neural Progenitor Cells Derived from Induced Pluripotent Cells on the Course of Acute Ischemic Stroke in Rats.

We compared the effects of placental mesenchymal stromal cells and neural progenitor cells derived from induced human pluripotent cells after their intravenous administration to rats in 24 h after transitory occlusion of the middle cerebral artery. The therapeutic effects were evaluated by the dynamics of animal survival, body weight, neurological deficit, and the volume of infarction focus in 7, 14, 30, and 60 days after surgery. Intravenous injection of neural progenitor cells produced a therapeutic effect on the course of experimental ischemic stroke by increasing animal survival in the most acute period and accelerating compensation of neurological deficit and body weight recovery.

[Use of multiparametric magnetic resonance imaging in t-staging of prostate cancer: a multicenter study].

Aim: The study aimed to analyze the diagnostic performance of preoperative multiparametric magnetic resonance imaging (mp-MRI) in the staging of prostate cancer (PCa) versus postoperative histological examination and determine the most sensitive pulse sequence from the mp-MRI protocol in estimating the local extent of PCa.

Materials And Methods: The study comprised 112 men aged 52 to 84 years with a morphologically verified diagnosis of prostate cancer. All patients underwent pelvic mp-MRI before radical prostatectomy (RPE) no earlier than six weeks after the prostate biopsy.

Mono- and Combined Therapy of Metastasizing Breast Carcinoma 4T1 with Zoledronic Acid and Doxorubicin.

The efficiency of monotherapy with zoledronic acid (Resorba), doxorubicin, and their combination was studied on the model of metastasizing breast carcinoma in BALB/c mice. Doxorubicin monotherapy was accompanied by a significant increase in median survival up to 57 days (vs. 34 and 35 days in control groups); 27% animals survived for 90 days (duration of the study).

Cuprizone Model as a Tool for Preclinical Studies of the Efficacy of Multiple Sclerosis Diagnosis and Therapy.

To study demyelination and remyelination processes and their response to different drugs, a protocol for modeling multiple sclerosis using the copper chelator cuprizone was developed. Magnetic resonance imaging confirmed the presence of demyelination lesions on week 4 of 0.6% cuprizone-containing diet.

Modeling and integral X-ray, optical, and MRI visualization of multiorgan metastases of orthotopic 4T1 breast carcinoma in BALB/c mice.

A model of highly metastasizing orthotopic allogeneic breast carcinoma was reproduced and standardized in experiments on BALB/c mice. 4T1 cells characterized by high metastatic activity were transfected with red fluorescent protein (RFP) gene or firefly luciferase (Luc2) gene. Unmodified 4T1 cells and modified 4T1-RFP and 4T1-Luc2 cells were subcutaneously injected to mature female mice into the second mammary fat pads.

Treatment of poorly differentiated glioma using a combination of monoclonal antibodies to extracellular connexin-43 fragment, temozolomide, and radiotherapy.

Antitumor efficiencies of monoclonal antibodies to connexin-43 second extracellular loop (MAbE2Cx43), temozolomide, and fractionated γ-irradiation in the monotherapy mode and in several optimized combinations were studied in Wistar rats with induced C6 glioma. The survival of animals with glioma and the dynamics of intracerebral tumor development were evaluated by MRT. Temozolomide monotherapy (200 mg/m(2)) and isolated radiotherapy in a total dose of 36 Gy shifted the survival median from 28 days (no therapy) to 34 and 38 days, respectively; 100% animals died under conditions of temozolomide monotherapy and radiotherapy.

Visualization of experimental glioma C6 by MRI with magnetic nanoparticles conjugated with monoclonal antibodies to vascular endothelial growth factor.

We developed a method for obtaining iron oxide nanoparticles and their conjugation with monoclonal antibodies to vascular endothelial growth factor. The resultant vector nanoparticles were low-toxic and the antibodies retained their immunochemical activity after conjugation. The study was carried out on rats with intracranial glioma C6 on day 14 after its implantation.

[Antioxidant properties and membranotropic effect of certain derivatives of 1,4-dihydropyridine].

Interaction of alpha-tocopherol and 1,4-dihydropyridine with endoplasmic reticulum membranes and model systems, human serum albumin and phospholipid bilayer, was studied using the microcalorimetry and fluorescent probes procedures. Dependence of microviscosity changes in the endoplasmic reticulum membranes on the place of antioxidants localization (protein structures or phospholipid phase) was shown. Increase of membrane structuralization under the influence of 1,4-dihydropyridines blocked their antioxidant action in spontaneous and induced lipid peroxidation.

[Antiradical and antioxidant properties of nonsteroidal anti-inflammatory agents--derivatives of pyridinecarboxylic acid].

A number of pyridincarboxylic acid derivatives PV-1-4, 7 and emoxypine preparation antioxidative activity in yolk lipoprotein suspension was studied by a method of Fe(2+)-initiated biochemiluminescence. Lipid peroxidation in suspension was effectively inhibited by the studied compounds in various concentration ranges. PV 1, 3, 4, 7 inhibited lipid peroxidation at the concentrations 100-fold, then those of PV 2 and emoxypine.

[Antiradical activity and membranotropic action of cardio- and vasotropic compounds of varying chemical nature].

Antiradical activity and ability to interaction with phosphatidylcholine bilayer of the physiological active compounds (PhAC), concerning the classes of phenylalkilamines (dobutamine, verapamil), dihydro pyridines (BAY-K-4688, nifedipine), analogues of crown ether (carbicyle, diol) was studied. By means of the method of microcalorimetry and spectrophotometry it was shown the complexing ability PhAC with the phospholipid bilayer of the model membrane. It was stated the simbasity in the changes of the thermal effect of the compounds with the negative inotropic activity during its reaction with phosphatidylcholine bilayer and antiradical activity.

[Antiradical and antioxidant activity of certain membranotropic substances of synthetic and plant origin].

Antiradical and antioxidative activities of dieton, phoridon, niphedipin, phlamicar, mildronat in vitro were studied by spectrophotometer's method with the use of dyfenilpycrilgydrasil and method of pulse voltametry. Also influence of drugs was studied under antioxidative insufficiency (AOI), which had modelled by exclusion of alpha-tocopherol from the animal's ration.

[Interaction of phenolic antioxidants and 1,4-dihydropyridines with membranes of rat liver microsome fractions].

Interaction of phenol type antioxidants and Ca-channel blockers, derivatives of 1,4-dihydropyridines, with rat liver microsomes has been studied in vitro by means of spectrophotometry and fluorescent probes using ANS and polymethine dye 4501 u. Incubation of microsomes in the absorption spectra of the antioxidant results in changes of structure dynamic parametres of microsomal membranes, and in changes of their microviscosity and in surface state modification. The mechanism of microsomal action was different for phenol type antioxidants and for 1,4-dihydropyridines and depended on the radical structure.

[Chromatin-protective action of the biologically active preparation BTK-8L in tetrachloromethane and chlorophos poisoning].

Results obtained from the study of the interaction between the phytosteroid preparation (BTK-8L) and fractionated rat liver nuclear chromatin under conditions of the tetrachloromethane and chlorophos intoxications are described. It is shown that preventive injection of BTK-8L to the animals has a partial protective effect on transcriptionally active and repressed liver chromatin. This preparation interacts with chromatin histone proteins binding with them and changes the nucleoprotein complex structure as a results of which the chromatin fraction components become less accessible to the damaging action of tetrachloromethane and chlorophos.

[Effect of stress on lipid peroxidation and physico-chemical status of endoplasmic reticulum membranes in liver of adult and old rats].

As a result of experiments carried out on adult (6-8 months) and old (24-26 months) male rats of the Wistar line it is established that emotional-pain stress results (in one day) in essential increase in the activity of spontaneous, NADPH--and ascorbate-dependent peroxidation of lipids in the liver microsomes, which is expressed in the old animals rather than in the adult ones. The induced peroxidation of lipid six days after the stress effect remains activated in the adult rats and decreases to the control level in the old ones. Accumulation of lipoperoxidation products in the membrane structure of hepatocytes is accompanied by the changes of physico-chemical parameters of microsomal membranes, microviscosity and surface potential in particular.

[Interaction of a substance based on phytoecdysteroids (BTK-8L) with components of fractionated chromatin from intact rat liver].

Results of the study of interaction of the phytoecdysteroid preparation (BTK-8L) with fractionated rat liver nuclear chromatin were described. It was shown that the interaction resulted in the "loosening" of the histone proteins structure both in active and repressed chromatin. At the same time the reparative DNA synthesis in the repressed fraction was stimulated.

[Genoprotective effect of drugs based on ecdysteroids in poisoning of rats with tetrachloromethane and chlorophos].

Molecular mechanisms of chromatin damage have been investigated during tetrachloromethane and chlorophos intoxication of experimental animals. Introduction of tetrachloromethane to experimental animals induced chromatin degradation causing a partial loss of histone H1-DNA fragmentation and formation of intermolecular bonds: DNA-protein. Intoxication with chlorophos results in repression of a part of genes due to augmented chromatin compactness.

[Antioxidant and antiradical activity of various classes of antioxidants].

Antiradical and antioxidative activities of classic phenolic antioxidants and blockers of Ca(2+)-channel have been studied. K2 rate constants and pI50 concentrations of tested physiologically active substances have been determined. Using the model systems of hepatic microsomal membranes lipoperoxidation it is shown that there is no distinct correlation between the antiradical and antioxidative activities of substances under investigation.

[Interaction of antioxidants with differing chemical structure with a phospholipid bilayer].

Interaction of antioxidant (derivatives of phenol and 1,4-dihydropyridine) with bilayer from lecithin was studied by means of electronic spectroscopy and microcalorimetry. The connection of warm effects and spectral properties was estimated by chemical structure of antioxidants. The effect of physiologically active compounds on the structural and dynamic parameters of the bilayer was determined by means of fluorescent probing.

[Lipid peroxidation and calcium transport in rat liver microsomes after chlorofos poisoning and the effect of atropine and verapamil].

Structural and functional state of rat hepatocytes endoplasmic reticulum membranes intoxicated with chlorofos (0,0-dimethyl-(1-oxy-2,2,21-trichloroethylphosphonate) was studied. It was shown that in case of intoxication a breakage of the membrane Ca(2+)-transport function was accompanied by modification of the membrane phospholipid lipoperoxidation processes and by conformational change of proteins. It is established that prophylactic injection of m-cholinolytic atropine and Ca(2+)-channel antagonist verapamil lead to normalization of processes of ATP-dependent potassium ion transport and lipid peroxidation processes (LPO) in the liver microsomal membranes of intoxicated animals.

[Mechanisms of the genoprotective action of a phytoecdysteroid drug (BTK-8L) in chromatin damage by chlorofos].

Genoprotective effect of preparation BTK-8L from plant steroids at prophylactic injection to experimental animals at chromatin damage by chlorofos was revealed. Antioxidant action of the preparation, being most highly expressed in the transcriptionally active chromatin fraction, is, probably, the most likely mechanism of the action. The realization of this action might be carried out as a result of the direct binding of BTK-8L with the chromatin protein-lipid complex, which was revealed during the analysis of the model systems showing binding of the preparation with chromatin fractions in vitro.

[Mechanisms of genoprotective action of a phytoecdysteroid drug(BTK-8L) in chromatin damage by tetrachloromethane].

Hepatoprotective action of prophylactic injection of aqueous solution of preparation BTK-8L from plant ecdysteroids to experimental animals with the liver damage by tetrachloromethane was revealed. This effect at least partially was connected with the genoprotective action of the given preparation. As a result, normalization of free radical chromatin lipid peroxidation reaction, modified at the intoxication, as well as partial correction of physical and chemical properties of chromatin protein-lipid complex were those molecular mechanisms of genoprotective action of BTK-8L, which were manifested by the influence of the preparation on such indices which characterized the depth structure of the complex as microviscosity and energy transfer from the protein to the lipid probe.