The neuroleptic activity of haloperidol increases after its solubilization in surfactant micelles. Micelles as microcontainers for drug targeting

It has been suggested to use surfactant micelles as microcontainers for increasing the efficiency of neuroleptic targeting from blood flow into the brain. The neuroleptic action of haloperidol, intraperitoneally injected into mice in micellar solution of non-ionic block copolymer surfactant (pluronic P-85) in water, increased several-fold if compared with that observed for haloperidol aqueous solution. Incorporation of brain-specific antibodies into haloperidol-containing micelles resulted in additional drastic increase (more than by 2 orders of magnitude) in the drug effect.     

Optimal method of isolation of supra-epithelial mucous layer of the small intestine in experimental animals

Experimental data on the activity of digestive endo- and exo-hydrolases in supra-epithelium mucus layer has been presented. Mucus layer has been obtained on special vibrating setting from the turned out intestinal preparation. Different conditions of work and medium of isolation have been used. The setting permits to obtain intestinal supra-epithelium mucus more completely and also prevents epithelium damages and hiting of damaged villi.     

Fatty acid acylated Fab-fragments of antibodies to neurospecific proteins as carriers for neuroleptic targeted delivery in brain.

A method for targeted delivery of neuroleptics from blood in brain based on using Fab-fragments of antibodies to antigens of brain glia cells (acid gliofibrillar antigen and alpha 2-glycoprotein) is suggested. The essence of the technique is that the molecule of neuroleptic (trifluoperazine) is conjugated with Fab-fragments of these antibodies. The conjugate thus obtained is modified by stearoylchloride in the system of Aerosol OT reversed micelles in octane. The study of the distribution of 125I-labelled conjugates in the rat organism after intracordial introduction is performed. On the contrary to the nonmodified conjugates and conjugate, containing fatty acylated Fab-fragments of antibodies, nonspecific to the rat brain, the conjugate of trifluoperazine with stearoylated Fab-fragments of antibodies to neurospecific antigens accumulate in brain tissues. The drastic increase of the neuroleptic activity of trifluoperazine resulting from its coupling with stearoylated Fab-fragments of antiglial antibodies is observed.     

The Transmembrane Protein of the Human Endogenous Retrovirus - K (HERV-K) Modulates Cytokine Release and Gene Expression

Numerous copies of endogenous retroviruses are present in the genome of mammals including man. Although most of them are defective, some, e.g., the human endogenous retroviruses HERV-K, were found to be expressed under certain physiological conditions. For instance, HERV-K is expressed in germ cell tumours and melanomas as well as in the placenta. Most exogenous retroviruses including the human immunodeficiency virus HIV-1 induce severe immunodeficiencies and there is increasing evidence that the transmembrane envelope (TM) proteins of these retroviruses may be involved. We show here that HERV-K particles released from a human teratocarcinoma cell line, a recombinant TM protein and a peptide corresponding to a highly conserved so-called immunosuppressive domain in the TM protein of HERV-K inhibit the proliferation of human immune cells, induce modulation of the expression of numerous cytokines, and modulate the expression of cellular genes as detected by a microarray analysis. The changes in cytokine release and gene expression induced by the TM protein of HERV-K are similar to those found previously induced by the TM protein of HIV-1. These data suggest that the mechanism of immunosuppression may be similar for different retroviruses and that the expression of the TM protein in tumours and in the placenta may suppress immune responses and thus prevent rejection of the tumour and the embryo.     

The spectrum of mutations and methods for their detection in the phenylalanine hydroxylase gene in phenylketonuria patients from the novosibirsk region

Phenylketonuria (PKU) is a widespread autosome recessive hereditary disease caused by a deficiency of the liver enzyme phenylalanine hydroxylase, which results in distortion of metabolism of phenylalanine and accumulation of toxic metabolites. The knowledge of molecular bases of PKU is of a high social importance as it enables phenotypic correction of the disease in the case of its early diagnostics. This disease is known to be associated with mutations in the phenylalanine hydroxylase gene, the distribution and mutation spectrum having pronounced ethnic and regional features. We studied the spectrum of mutations in the phenylalanine hydroxylase gene in a group of patients with PKU from the Novosibirsk region to reveal 10 missense point mutations, 1 mutation in the splice donor site, and 1 microdeletion. For these mutations, most widely distributed in the region, we used straightforward detection methods basing on the restriction fragment length polymorphism (RFLP), artificial constructed restriction sites (ACRS) PCR, and denaturing gradient gel electrophoresis (DGGE).     

Marital Structure,Genetic Fitness,and the <Emphasis Type="Italic">GJB2</Emphasis> Gene Mutations among Deaf People in Yakutia (Eastern Siberia,Russia)

Autosomal recessive deafness type 1A (DFNB1A) caused by mutations in the GJB2 gene (Cx26) is the main cause of nonsyndromic hearing impairment in many populations worldwide. It is considered that widespread prevalence of DFNB1A can be due to the long tradition of intermarriages between deaf people (assortative marriages) combined with their increased social adaptation and genetic fitness after widespread introduction of sign language. For the first time, the data on mating structure and reproduction of deaf people living in Yakutia (Eastern Siberia, Russia) are presented in comparison with contribution of the GJB2 gene mutations to the etiology of hearing impairment. The relative fertility of deaf people compared to their hearing siblings is 0.78 (mean number of children 1.76 ± 0.10 and 2.24 ± 0.09 to deaf and their hearing siblings, respectively, p = 0.0018). The rate of assortative marriages among deaf people is 77.1% (81 of 105 marriages). Biallelic mutations in the GJB2 gene were found in 42.2% (43 of 102) of examined deaf people, which corresponded to diagnosis DFNB1A for these patients. A comparison of deaf marital partners by GJB2 status revealed a proportion of noncomplementary marriages (24%) in which hearing loss in both partners was caused by the presence of biallelic GJB2 gene mutations resulting in the birth of only deaf children in such couples. Thus, the set of obtained data including a relatively high genetic fitness (expressed as relative fertility) of deaf people in Yakutia in combination with a high rate of assortative marriages among them and high incidence of DFNB1A indicates a possible weakening of selection against such trait as “deafness” and a possible increase in the frequency of GJB2 mutant alleles in subsequent generations.     

Halobacterium salinarum storage and rehydration after spray drying and optimization of the processes for preservation of carotenoids

Extremophiles - Spray drying is appropriate for the preservation of halophilic microorganisms due to the nature of these microorganisms, as they survive in adverse environmental conditions by being...     

Seasonal changes in hepatic antioxidant enzyme activities of the perch <Emphasis Type="Italic">Perca fluviatilis</Emphasis> in the Upper Volga basin,Russia

Seasonal changes in several physiological endpoints of the perch Perca fluviatilis in the temperate climatic conditions were examined. Hepatic antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione-S-transferase) varied dramatically throughout the annual cycle. Driven by internal and external factors, the greatest values of the studied characteristics were timed to the periods of spawning and elevated water temperature. The results of this study showed high plasticity of the fish’s antioxidant system, which allows the perch to bear naturally occurring oxidative stress.     

N-(5′-Phosphopyridoxyl)glutamic acid and N-(5′-phosphopyridoxyl)-2-oxopyrrolidine-5-carboxylic acid and their action on the apoenzyme of aspartate aminotransferase

1. N-(5'-Phosphopyridoxyl)-l-glutamic acid (P-Pxy-Glu, compound I) is readily converted at pH3 into a substance (P-Pxy-Glp, compound II) characterized as N-(5'-phosphopyridoxyl)-2-oxopyrrolidine-5-carboxylic acid. 2. The u.v., i.r. and fluorescence spectra of P-Pxy-Glu and P-Pxy-Glp have been determined; from the u.v. spectra their pK values have been found and compared. 3. The apoenzyme of aspartate aminotransferase is rapidly and irreversibly inactivated by P-Pxy-Glu, but is inactivated more slowly by P-Pxy-Glp. The complex with P-Pxy-Glp is stable enough to be isolated, but it is slowly reactivated in the presence of excess of pyridoxal phosphate. 4. The u.v. spectrum of the complex of apoenzyme and P-Pxy-Glp suggests that it contains a hydrogen bond between the phenolic hydroxyl group and the pyrrolidone nitrogen; this specifies the conformation of most of the molecule of P-Pxy-Glp. This conformation is similar to that previously postulated for the enzyme-glutamate complex except for the side chain of glutamate. Hence both the affinity of P-Pxy-Glp for the apoenzyme and the fact that it is more easily removed than P-Pxy-Glu are explicable.