Statistical properties of extreme soliton collisions.

Synchronous collisions between a large number of solitons are considered in the context of a statistical description. It is shown that, during the interaction of solitons of the same signs, the wave field is effectively smoothed out. When the number of solitons increases and the sequence of their amplitudes decay slower, the focused wave becomes even smoother and the statistical moments get frozen for a long time. This quasi-stationary state is characterized by greatly reduced statistical moments and by the density of solitons close to some critical value. This state may be treated as the small-dispersion limit, what makes it possible to analytically estimate all high-order statistical moments. While the focus of the study is made on the Korteweg-de Vries equation and its modified version, a much broader applicability of the results to equations that support soliton-type solutions is discussed.

Increased Expression of the Multimerin-1 Gene in α-Synuclein Knokout Mice.

Multimerin-1 (Mmrn-1) is a soluble protein, also known as elastin microfibril interfacer 4 (EMILIN-4), found in platelets and in the endothelium of blood vessels. Its function and role in pathology are still not fully understood. Genetic modifications in alpha-synuclein gene (Snca) locus that mapped 160 Kb apart from Mmrn-1 in mouse genome, could weigh with regulatory elements of Mmrn-1 gene. We have studied the Mmrn-1 expression in brain cortex of three mouse lines with Snca knock-out: B6(Cg)-Sncatm1.2Vlb/J, B6;129-Sncatm1Sud/J, and B6;129X1-Sncatm1Rosl/J. The 35-fold increase for Mmrn-1 mRNA level have been found in B6;129X1-Sncatm1Rosl/J mice that carry in their genome foreign sequences including bacterial gene neo and a strong promoter of a mouse phosphoglycerate kinase (Pgk1) oriented towards Mmrn-1 gene. This effect on regulatory elements of Mmrn-1 gene as a result of modifications in Snca locus should be taken into consideration when using B6;129X1-Sncatm1Rosl/J line, that is widely applied for study of neurodegeneration mechanisms.

Synuclein Deficiency Decreases the Efficiency of Dopamine Uptake by Synaptic Vesicles.

In the present study, we analyzed the uptake of radiolabeled dopamine by intact synaptosomes and purified synaptic vesicles isolated from the dorsal striatum of mice with constitutive inactivation of all three synuclein-coding genes and wild-type mice. Synuclein deficiency substantially compromised the uptake of this neurotransmitter by synaptic vesicles but had no effect on synaptosomal dopamine uptake.

The role of alpha-synuclein in the development of the dopaminergic neurons in the substantia nigra and ventral tegmental area.

Alpha-synuclein is a presynaptic protein of vertebrates that belongs to the family of synucleins. Normal functions of synucleins remain unknown. Alpha-synuclein is one of the causative factors of the familial and idiopathic forms of Parkinson's disease (PD). The progressive loss of dopaminergic (DA) neurons is characteristic of PD and the most severe damage occurs in the substantia nigra (SN). This leads to an erraticism of the synthesis and synaptic secretion of the neurotransmitters, subsequently resulting in the loss of the connections between brain areas. This work shows that alpha-synuclein is directly involved in the formation of the mature DA neurons of the midbrain at different stages of the ontogenesis and these findings are consistent with data obtained in other studies. Thus, alpha-synuclein may have a varying modulating effect on the growth dynamics and the fate of populations of DA neurons.

The new line of genetically modified mice with constitutive knockout of the gene alpha synuclein to study pathogenetic aspects of differential loss of dopaminergic neurons .

The purpose: This study investigated the role of alpha-synuclein in the development of dopaminergic neurons. Methods: In this study a new SNCA knockout mouse line has been used to model the deficiency of alpha-synuclein function. In the knockout and control mice the dynamics of the formation of two distinct populations of dopaminergic neurons differently affected in patients with PD was studied by the comparative morphometric analysis. Results: Here, we revealed a prominent modulating effect of alpha-synuclein on the developing DA neurons in substantia nigra (SN) which is the most affected region in PD patients. Yet, alpha-synuclein had no effect on the formation of DA neurons in ventral tegmental area which is much less susceptible to degeneration in PD patients. Conclusion: The new line of knockout mice is a convenient model for studying pathophysiologic aspects of selective impairment of DA neurons.

[A mice model of amyotrophic lateral sclerosis expressing mutant human FUS protein].

UNLABELLED: BACKGROUND AND ОBJECTIVE: Loss of conformation and function of sufficient number of proteins with high aggregation capacity plays an important role in the pathogenesis of many neurodegenerative disorders (NDD). Due to a recent discovery of new array of proteins with the capacity to form aggregates of nonamyloid type, new NDD models as well as a new level of understanding in vivo models which are already exist is needed. DNA/RN A binding proteins - FUS and TDP-43 play a crucial role in the pathogenesis of some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. The objective of the study was to develop a new ALS transgenic model. MATERIAL AND METHODS: In cell culture experiments, we studied mutant FUS proteins capable to form intracellular deposits morphologically similar to those observed in the autopsy material of ALS patients. RESULTS AND CONCLUSION: We created a transgenic mice line, in which a pathogenic form of human FUS protein was expressed in the nervous system. That led to the aggregation of FUS protein in spinal cord and motor neurons with the following degeneration and development of a phenotype, similar to the human ALS disease phenotype, in young grown-up animals. This neurodegenerative phenotype corresponds to a great number of clinical manifestations of human ALS and is an adequate transgenic model of the disease.

[Study into molecular targets of a neuroprotective compound dimebon using a transgenic mice line].

In the present study we have used a transgenic mice overexpressing an amyloidogenic protein, gamma-synuclein, in the nervous system to address the effect of dimebon on proteinopathy progression. Neuroprotective effect of chronic dimebon administration in these mice at organismal level was confirmed by the increased lifespan. Using histological and biochemical approaches we have demonstrated that dimebon reduced the number of amyloid inclusions in spinal cord of transgenic animals and decreased the content of ubiquitinated proteins in detergent-insoluble fractions. These effects are likely to occur at the level of aggregated protein species, since transgene expression was not altered. Thus, pathological protein aggregation serves as one of dimebon targets in neurodegeneration.

[Parameters of oxidative stress in patients with gastric cancer].

We studied effect of the neoplastic process and surgical treatment on parameters of the oxidative system in patients with stomach cancer including serum and gastric tissue levels of malonic dialdehyde, lactic and pyruvic acids in stage I-IV malignancy before and after radical surgery. The development and generalization of the neoplastic process are associated with the activation of oxidative reactions leading to endotoxicosis. Specific anticarcinogenic treatments (including surgery) aggravate changes in the oxidative systems and further deteriorate quality of life and tolerance of the treatment.

[Studying efficacy of remaxol in the treatment of respiratory distress syndrome under endotoxicosis conditions].

Chronic model experiments on dogs showed that the development of respiratory distress syndrome under acute pancreatitis conditions is correlated with violation of metabolic processes in the lung tissue, which is caused by activation of the coagulation/lysis system and changes in the lipid metabolism. It is established that remaxol limits the development of inflammatory processes in lungs, produces correction of the lipid metabolism, and introduces positive changes in the coagulation system lung tissues under acute pancreatitis conditions.

[Prevention of ulcerogenesis at experimental pancreatitis].

OBJECTIVE: We wanted to study the mechanisms of "Dimefosfon" influence on ulcerogenesis prevention in acute pancreatitis. MATERIALS AND METHODS: The study was conducted on 36 dogs. We were modeling of edematous form of pancreatitis: fulfilled the median laparotomy, punctured of the gall bladder bile were taken, it was administered at 5 points of the pancreas parenchyma to 0.5 ml. The animals of experimental group on a daily basis once a day for 5 days were administered intravenously 15% solution of dimefosfon the rate of 50 mg/kg body weight. In the tissues of the duodenum was examined the intensity of lipid peroxidation, determined indicators of hypoxia, transcapillar exchange and bioenergy, and conducted their microscopic examination. RESULTS: Dimefosfon helped to reduce the severity of inflammation in the pancreas parenchyma, as well as the destructive changes in the duodenum. Dimefosfon effectiveness in correction of microcirculation, trophic system and bio-energy disorders in the tissues of intestine was shown by the third day of the drug using. At this period the capillary filtrate, the diffusion coefficient of oxygen, the rate of electrogenesis duodenal tissues significantly exceeded results of the control group study. Indicator protein loss wasn't significantly different from controls. Efficiency of dimefosfon in correction indicators of hypoxia was also seen with the third day of therapy. In duodenal tissue during this period there was a decrease of lactate and pyruvic acid as compared with control. Significant changes in indicators of intensity of lipid peroxidation and the activity of phosfolipase A2 in duodenal tissues were observed on the third day of dimefosfon using. At this stage of observation resultes were compared with the control and had decreased of malondialdehyde content and activity of phosfolipase A2. Catalase activity was lower compared with the control and did not differ from the norm. CONCLUSION: One of the ulcerogenesis mechanisms in duodenum in acute pancreatitis is a violation of microcirculation, deterioration trophics tissues of the intestinal wall that contribute to the launch of free radical reactions and lead to membranodestructive processes in the intestinal mucosa. Dimefosfon has cytoprotect effect as a result of decreased activity of lipid peroxidation and restoration of microcirculation and trophics tissues of intestinal wall. Positive therapeutic effect of the drug was observed with the third day of therapy.

[Mexidol-induced modification of lipid metabolism in pancreatitis]. / Modifikatsiia obmena lipidov pri pankreatite pod vliianiem meksidola.

The chronic experiments on mongrel dogs with a model pancreatitis showed that mexidol decreases manifestations of the inflammatory process. The treatment with mexidol led to a decrease in the degree of lipid transformations in the initial stage of pancreatitis development, with normaliation of the lipid metabolism according to the liver and blood plasma characteristics. The membranoprotector effect of mexidol, manifested in normalization of the lipid spectrum, is probably related to inhibition of the lipid peroxidation (LPO) process and to a decrease in the activity of phospholipase A2. The correlation between lipid metabolism, LPO, and phospholipase A2 activity in the tissues studied indicates that the therapeutic effect of mexidol in animals with pancreatitis is based on the cytoprotector activity of the drug.

[Effect of antioxidants on endotoxicosis in experimental peritonitis]. / O vliianii antioksidantov na vyrazhennost' éndotoksikoza pri éksperimental'nom peritonite.

The chronic experiments on dogs with a peritonitis model showed that drugs possessing antioxidant properties (vitamin E, dimephosphon, xymedone) are capable of decreasing the inflammatory phenomena in abdominal cavity and decreasing the expression of endogenous intoxication, as manifested by a decrease in the plasma toxicity and the content of average-molecular-weight peptides and lipid peroxidation products. The most pronounced positive effect was observed for xymedone. A certain correlation between the effects of antioxidants upon endotoxicosis and free-radical lipid peroxidation reactions was established. This result suggests the therapeutic effect of antioxidants used for the treatment of peritonitis is related to their membrane-stabilizing ability.