Study of xanthine oxidase activity in the brain tissue after administration of dalargin during myoplegia

Effect of Dalargin (40 micrograms/kg) on xanthine-oxidase (X) activity in experimental Arduan-induced myoplegia (0.1 mg/kg) was studied in the brain tissue of 70 rats under inhalation anesthesia and artificial ventilation. Neither Dalargin nor Arduan was found separately to induce statistically significant changes in X activity. Dalargin injections in myoplegia caused significant (24.7%) reduction of the enzyme's activity.     

Liposome formulations of combretastatin A4 and its 4-arylcoumarin analogue prodrugs: The antitumor effect in the mouse model of breast cancer

The antimitotic agent combretastatin A-4 (CA-4) has been recently proposed as an antivascular agent for anticancer therapy. In order to reduce systemic toxicity by means of administration in liposome formulations, new lipophilic prodrugs, oleic derivatives of CA-4 and its 4-arylcoumarin analogue (CA4-Ole and ArC-Ole, respectively), have been synthesized in this study. Liposomes with mean diameter of 100 nm prepared on the basis of egg phosphatidylcholine and baker’s yeast phosphatidylinositol quantitatively included up to 15 mol% of CA4-Ole, or 7 mol% of ArC-Ole. To achieve targeting to neovascular endothelium prodrug bearing liposomes decorated with the tetrasaccharide selectin ligand Sialyl Lewis X (SiaLeX) have been also prepared. The antitumor activity was studied in vivo using the model of slow-growing mouse breast cancer. Under the dose used (22 mg/kg) and the administration protocol (four injections, one per a week, starting from the appearance of palpable tumors) cytostatic CA-4 did not reveal any anticancer effect; moreover, it even stimulated tumor growth. The liposome formulations of CA4-Ole did not demonstrate such stimulation. However, to achieve a pronounced antitumor effect, the number of injections of liposomes should be apparently increased. The cytotoxic activity of a novel antimitotic agent ArC was one order of magnitude lower in the human breast carcinoma cell culture in vitro. Nevertheless, in vivo in the mouse model of breast cancer the antitumor effect of this compound corresponded to the double equivalent dose of CA-4. The results demonstrate perspectives of SiaLe^X-liposomes loaded with ArC-Ole: the preparation partially inhibited tumor growth already after the second injection. Thus, subsequent optimization of doses and regimens of administration both for ArC and liposomal ArC-Ole formulations are needed.     

Lipophilic prodrugs of a triazole-containing colchicine analogue in liposomes: Biological effects on human tumor cells

Colchicine site binders—blockers of tubulin polymerization—are potential antimitotic agents for anticancer therapy. To reduce their systemic toxicity and improve biodistribution, encapsulation in nanosized liposomes may be employed. Liposomes present a convenient means for preparation of injectable for-mulations of hydrophobic compounds, however colchicine as such is known to leak through the lipid bilayer. In this study, newly synthesized triazole-containing analogues of colchicine and allocolchicine, and their palmitic and oleic esters (lipophilic prodrugs) were tested for anti-proliferative activity and apoptosis-inducing potential. In contrast to colchicine conjugates, whose activities ranged with those of colchicine, allocolchicine derivatives exhibited drastically lower effects and were discarded. Liposomes of about 100 nm in diameter composed of egg phosphatidylcholine-yeast phosphatidylinositol-palmitic or oleic prodrug, 8: 1: 1, by mol, were prepared by standard extrusion technique and tested in a panel of four human tumor cell lines. Liposome formulations preserved the biological activities of the parent colchicinoid the most towards human epithelial tumor cells. Moreover, liposomal form of the oleoyl bearing colchicinoid inhibited cell proliferation more efficiently than free lipophilic prodrug. Due to substantial loading capacity of the liposomes, the dispersions contain sufficient concentration of the active agent to test wide dose range in experiments on systemic administration to animals.     

Hereditary Diseases of Nervous System in the Population of Vladimir Oblast

The first population genetic study of hereditary disorders of the nervous system (HDNS) in Vladimir oblast was carried out. A total of 1622900 subjects, including 1306200 from the urban and 316700 from the rural population, were tested. The population examined was characterized by virtually homogenous ethnic structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in Vladimir oblast corresponded to the average prevalence for other Russian populations. Substantial differences between urban and rural populations in respect of the population load of HDNS and its nosological structure were not observed. A total of 22 nosological forms of HDNS were revealed, including thirteen autosomal dominant (193 families with 272 affected individuals), seven autosomal recessive (59 families with 66 affected individuals), and two X-linked (15 families with 17 affected individuals) diseases. The composition of the HDNS spectrum nucleus in Vladimir oblast displayed a number of differences from that in the majority of other populations examined. The HDNS in different regions of the area tested were characterized by different prevalence and spectrum. The data obtained may constitute a basis for regional registration of HDNS in Vladimir oblast.     

Hereditary diseases of nervous system in the population of Vladimir province

The first population genetic study of hereditary disorders of the nervous system (HDNS) in Vladimir oblast was carried out. A total of 1,622,900 subjects, including 1,306,200 from the urban and 316,700 from the rural population, were tested. The population examined was characterized by virtually homogenous ethnic structure, with Russians constituting 95.76%. Pooled prevalence of HDNS in Vladimir oblast corresponded to the average prevalence for other Russian populations. Substantial differences between urban and rural populations in respect of the population load of HDNS and its nosological structure were not observed. A total of 22 nosological forms of HDNS were revealed, including thirteen autosomal dominant (193 families with 272 affected individuals), seven autosomal recessive (59 families with 66 affected individuals), and two X-linked (15 families with 17 affected individuals) diseases. The composition of the HDNS spectrum "nucleus" in Vladimir oblast displayed a number of differences from that in the majority of other populations examined. The HDNS in different regions of the area tested were characterized by different prevalence and spectrum. The data obtained may constitute a basis for regional registration of HDNS in Vladimir oblast.     

Pathogenetic role of intestinal microbiocenosis in the pathogenesis of hereditary myodystrophy

The effect of the inclusion of probiotic preparations for the correction of disturbances in normal intestinal microflora into the complex therapy of patients wish Duchenne's childhood muscular dystrophy and Becker's myopathy was analyzed. Probiotic therapy made it possible to improve the clinical state of patients, manifested by an increase in muscular strength and accompanied by positive shifts in electromyographic, immunological, biochemical, hormonal characteristics. Intestinal microbiocenosis plays seemingly a certain role in the formation of hereditary pathology.     

Dynamics of electrostatic fluctuations in the edge plasma in the U-3M torsatron

Results are presented from experimental and theoretical investigations of oscillatory and wave phenomena observed in the edge region in the U-3M torsatron during plasma creation and heating by an RF discharge in the ICR frequency range, accompanied by a transition to improved confinement. The main results are reported of diagnostic measurements of the spectral composition of oscillations, as well as of how the phase and amplitude relationships depend on time and on the RF power during its injection into the plasma. The measurements were carried out with electrostatic probes positioned at the edge of the plasma confinement region. The experimental results are interpreted using the kinetic theory of the electron-ion parametric instability of a plasma in the ion cyclotron frequency range and are compared with the results of numerical simulations.