Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10

The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain.     

Synthesis,toxicity, and percutaneous activity of silicon glycerolates and related hydrogels

Silicon glycerolates of the general formula Si(C₃H₇O₃)₄ ⋅ xC₃H₈O₃(3 ≤ x ≤ 10) and related hydrogels of the general formula Si(C₃H₇O₃)₄ ⋅ xC₃H₈O₃ ≤ yH₂O (3 ≤ x ≤ 10, 20 ≤ y ≤ 40) were synthesized and some of their pharmacological properties were studied. The laws of gel formation were investigated and optimum conditions for the process were determined. High percutaneous (transdermal) activity of the synthesized compounds was revealed by measuring the diffusion of drugs through intact skin membrane in vitro. The acute and chronic toxicity was studied. It was established that all substances are nontoxic. The experimental results show that silicon glycerolates and related hydrogels can be recommended for further testing and investigation as effective biologically active percutaneous vehicles of medicinal preparations. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 11, pp. 5–9, November, 2008.     

Comparison of the Temporary Dynamics of NGF and BDNF Gene Expression in Rat Hippocampus,Frontal Cortex,and Retina Under Semax Action

Neurotrophins are a family of structurally related proteins that regulate the survival, differentiation, and maintenance of function of different neuron populations. Some peptides are able to affect the production and activity of neurotrophins. One of these synthetic peptides is heptapeptide Semax, an analog of the N-terminal adrenocorticotropic hormone fragment 4-10. It is known that Semax has effects on learning and memory formation and exerts some neuroprotective effects in rodents and humans. Male Wistar rats were treated for 20 min, 40 min, 90 min, 3 h, 8 h, and 24 h with Semax. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in rat brain and retina was analyzed by real-time polymerase chain reaction. It was revealed that after Semax administration the multidirectional activation of the expression of the genes under investigation in the hippocampus, frontal cortex, and retina was observed. The expression of both neurotrophin genes was decreased in rat hippocampus and retina 20 min after Semax administration and was increased in the frontal cortex. The expression levels of NGF remained practically constant in the retina at the initial stage, whereas the expression levels of BDNF were significantly increased 90 min after Semax administration.     

Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic Russian individuals from Moscow,Russia

Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms. Genotype data are available in the Allele Frequencies Net Database under identifier AFND 3367 and the population name “Russia Moscow Cytokine”.     

Polymorphisms of genes involved in inflammation and blood vessel development influence the risk of varicose veins

Heredity plays an important role in the etiology of varicose veins (VVs). However, the genetic basis underlying this condition remains poorly understood. Our aim was to replicate top association signals from genome‐wide association studies (GWASs) for VVs of lower extremities using 2 independent datasets—our sample of ethnic Russian individuals (709 cases and 278 controls) and a large cohort of British residents from UK Biobank (10 861 cases and 397 594 controls). Associations of polymorphisms rs11121615, rs6712038, rs507666, rs966562, rs7111987, rs6062618, and rs6905288 were validated in the UK Biobank individuals at a Bonferroni‐corrected significance level. In Russian cohort, only rs11121615 reached a nominal significance level of P < .05. Results of original GWAS and replication studies were combined by a meta‐analysis, and polymorphisms listed above as well as rs111434909 and rs4463578 passed a genome‐wide significant threshold. Notably, the majority of these polymorphisms were located within or near genes involved in vascular development and remodeling, and regulation of inflammatory response. Our results confirm the role of these polymorphisms in genetic susceptibility to VVs and indicate the revealed genomic regions as good candidates for further fine‐mapping studies and functional analysis. Moreover, our findings implicate inflammation and abnormal vascular architecture in VVs pathogenesis.     

Seasonal aspects of the oxidative stress in Northeners]

Evaluated were consequences of changes in oxygen demand, bronchial conduction, exercise performance, functioning of antioxidant enzymes and body provision with natural oxidants for the level of free-radical oxidation products in human organism. To this end, a group of essentially healthy young male northerners spending much time outdoors was surveyed over a one-year period. Among the listed parameters oxidation of free radicals was particularly sensitive to seasonal insufficiency of some of the antioxidant enzymes.     

Methods of limb elongation with congenital inequality in children

During the period 1973-1978 elongation with a distraction-compression apparatus was performed on 78 children with congenital limb length inequality. The length of follow-up ranged from 2 to 6 years. Inequality in limb length measured 4 to 6.5 cm in 51 children, 6.5 to 8 cm in 24, and more than 8 cm in three. The final results in 72 children were judged satisfactory in that equal limb length was obtained. Equalization was accomplished with lengthening up to 6 cm in a one-stage procedure; lengthening greater than 6 cm was accomplished in two stages. During distraction two fractures and six pin tract infections occurred; four patients with joint stiffness adjacent to the segment under elongation required additional measures.