Effect of Cell-Penetrating Arginine Peptide on Interaction of Photosensitizer Chlorin e6 Incorporated into Phospholipid Nanoparticles with Tumor Cells.

We studied the possibility of increasing the efficiency of photodynamic therapy by improving delivery of photosensitizers chlorin e6 into tumor cells. Previous studies showed that incorporation of chlorin e6 onto phospholipid nanoparticles with a diameter <20 nm reduces its cytotoxicity due to accelerated elimination from organs [8]. A heptapeptide R7 synthesized and added to this combination promoted internalization of chlorin e6 into HepG2 cells in comparison with initial nanoparticles without peptide R7. The observed effect of peptide R7 can be explained by activation of endocytosis and/or macropinocytosis (bearing in mind the interaction of arginine with carboxyl groups of e6. The development of this transporting system is a promising trend in photodynamic therapy of cancer diseases.

[Contribution of hemodynamic disturbances in magistral vessels to optic neuropathy progression and ocular tension changes in endocrine ophthalmopathy].

AIM: to investigate the contribution of various hemodynamic disturbances in magistral vessels to optic neuropathy (ON) progression and ocular tension changes in endocrine ophthalmopathy (EOP). MATERIAL AND METHODS: A total of 39 patients (78 eyes) with subclinical EOP (clinical activity score, CAS ≤ 2) associated with Graves' disease (n = 32, 64 eyes) or autoimmune thyroiditis (n = 7, 14 eyes) were examined. Orbit echography was performed in all patients. Blood flow was assessed with a Voluson 730 PRO ultrasound diagnostic system ("Kretz", Austria) in triplex mode (B-scan, color Doppler flow mapping in combination with pulse-wave Doppler). Thus obtained hemodynamic parameters in ophthalmic artery, central retinal artery (CRA), central retinal vein (CRV), short posterior ciliary arteries (SPCA), and long posterior ciliary arteries (LPCA) were analyzed. To reveal the role of hemodynamic disturbances in the above mentioned vessels in ON progression and eye pressure maintenance, the patients were divided into 7 groups. Only those eyes, whose peripheral indices were increased by more than 25% of normal values and diastolic blood flow decreased by not less than 25%, were selected for further study. Intraocular pressure changes were evaluated by group mean (Mmean = M ± m mmHg), optic neuropathy progression--by the difference in group mean depth (dB) and number of scotomas between the first and the last visit (6 months of observation). RESULTS: In almost all types of perfusion disturbances, the resultant chronic ocular ischemia causes a decrease in IOP. The only exception, as shown, is simultaneous involvement of CRA, SPCA, and LPCA. The level of blood flow disturbance determines the severity of qualitative and quantitative changes in eyes with EOP-associated ON. The rate of ON progression directly correlates with baseline IOP values on day zero. CONCLUSION: Long-lasting chronic impairment of blood supply of the eyeball leads to reduction in ocular tension and progression of optic neuropathy. Combined perfusion disturbances in CRA and LPCA as well as in CRA, LPCA, and SPCA can be considered a high-risk factor, while SPCA and/or LPCA involvement--a moderate-risk factor.

[Assessment of the size of the thalamus as a method for the evaluation of the activity of neurodegenerative process after the treatment with cerebrolisin in young patients with multiple sclerosis].

The aim of the study was to describe the atrophy of the thalamus in young patients with active relapsing multiple sclerosis (MS) treated with cerebrolysin. Eighteen MS patients (mean age 20.10±0.45 years) with disease onset in childhood or adolescence were studied. Neurological examination using the EDSS, neuropsychological testing and MRI were used. At baseline, MRI revealed the hypotrophy of the thalamus that was not correlated with the performance on neuropsychological tests. After treatment with cerebrolysin, there was the decrease in the level of atrophy that suggested the neuroprotective effect of this drug. This effect was more prominent in younger patients with the high frequency of previous relapses.

[Testing of microsatellite primers with different populations of Eurasian spruces Picea abies (L.) Karst. and Picea obovata Ledeb].

From a clone library containing microsatellite DNA fragments of Norwegian spruce, seven pairs of primers were selected. These primers were tested to be the markers in the genetic structure analysis of nine populations of Eurasian spruce species Picea abies (L.) Karst. and Picea obovata Ledeb. Five pairs of these primers identified polymorphic loci with the allele numbers from 6 to 15. In the populations examined, the observed and expected heterozygosity values assessed at five loci varied from 0.1778 to 0.6556 and from 0.7800 to 0.900, respectively. In the populations examined, the values of F(st) index varied from 0.0691 to 0.2551 with the mean value of 0.1318. On the dendrogram based on Nei genetic distances, the populations formed three groups: Pskov-Ciscarpathia, Komi-Tatarstan-Arkhangelsk, Kazakhstan-Karelia(natural)-Karelia(culture)-Krasnoyarsk. Five of the primer pairs tested proved useful for analysis of the population genetic structure in Eurasian spruce species.

[Effect of tests with dosed physical load on sinus node function and repolarization in children with hereditary long QT syndrome].

The study is devoted to assessment of effect of physical effort of sinus rhythm rate and the state of the process of repolarization in children with 1 and 2 molecular-genetic variants of the long QT syndrome (LQT). We have shown that LQT1 is characterized by inadequate increment of heart rate (HR) and substantial increase of QTc interval during exercise. In LQT2 compared with control reduction of HR increment also takes place while shortening of QTc interval is more pronounced. Delta QTc<0 is an important differential diagnostic criterion in patients with LQT1 and LQT2. Variatins in T wave morphology in LQT1 and LQT2 diminish at the background of physical exercise. The use of ß-blockers influences relationship between length of QT interval and HR in patients with LQT but does not eliminate distinction from a group of patients with analogous variant of the syndrome not taking these drugs.

[Hepatitis virus genotype structure in patients with chronic hepatitis C].

AIM: Studies of hepatitis C virus (HCV) genotype and subtype structure in patients with chronic hepatitis C in 3 regions of the Central federal district of Russia. MATERIALS AND METHODS: Hepatitis C virus genotype and subtype structure was determined in patients with chronic HCV infection in Moscow (1993 - 1995 and 2005), Moscow region (2008) and Vladimir region (1993 -1995, 2005-2007). HCV genotype was determined by using A. Widell et al. (1994) technique, PCR (AmpliSens diagnostic kits), Genotype C test system. RESULTS: In all studied regions and during all the time periods the first position in rating belonged to HCV 1b subtype. In 1993 - 1995 and 2005 - 2007 period changes in HCV genotype and subtype structure were registered that consisted of relative weight of 1b subtype decrease and 3a subtype increase. Subtype 1b in females with chronic hepatitis C was registered more often than in males. In Vladimir region 3a subtype in males was detected more often than in females. In males older than 30 years the first rating position belongs to 1b subtype and in males younger than 30 years--subtype 3a. In females older than 30 years in Moscow region and Vladimir region, as well as in females younger than 30 years in Vladimir region subtype 1b was detected more often, while in Moscow region HCV subtypes 1b and 3a were detected with the same rate of 47.6%. CONCLUSION: Currently there is an urgent need to include mandatory monitoring of hepatitis C virus genetic variants into the system of hepatitis C epidemiologic control in Russia. This approach will allow for a significant increase in quality of hepatitis C serological diagnostics, and can be used in the prognosis of evolution of the epidemic process of this disease.

[Diagnosis, sudden death risk stratification, and treatment of main long QT syndrome molecular-genetic variants].

Inherited long QT syndrome (LQTS) refers to the primary electrical diseases of the heart. It is characterized by QT prolongation on resting ECG and syncope due to life-threatening ventricular arrhythmias. This review focuses on diagnosis, differential diagnosis, risk stratification of sudden cardiac death, and treatment strategy of patients with most prevalent genetic fOrms of LQTS - LQT1, LQT2 and LQT3, which accounted for about 90% of all genetically confirmed cases. Recent advances in understanding of relationship between clinical, electrocardiographic features (on ECG, body surface mapping, stress test) and genetic variants of LQT presented. Characteristics of syncopal events and ECG features of LQTl, LQT2 and LQT3 in the majority of cases are helpful to make an appropriate choice for therapy, even before positive result of molecular genetic testing. Management has focused on the use of beta blockers as first-line treatment and exclusion of triggers of life-threatening arrhythmia which are specific for each molecular-genetic variant. Implantation of cardioverter defibrillator for secondary prevention of sudden death in the high-risk patients or patients with insufficient effect of antiarrhythmic therapy is required.

[Screening of population genetic SCAR markers for mykiss Parasalmo (Oncorhynchus) mykiss from Kamchatka].

Using AP-PCR, the genome of Kamchatka mykiss (Parasalmo (O.) mykiss) was examined. Polymorphic fragments, implying geographic differences among the samples, were selected, cloned, and sequenced. Based on these sequences, longer, specific SCAR primers were selected and constructed. Using the BLAST software program, the sequences were analyzed for analogy to those from the GenBank database. It seemed likely that all sequences obtained belonged to earlier unexamined repeated sequences, variable in the populations of the species of interest. A total of seven SCAR markers, characterized by population-significant variability of the DNA products in Kamchatka geographic group of rainbow trout were constructed. These markers can be used for further investigation of the species Parasalmo (O.) mykiss. The SCAR marker sequences were deposited in GenBank under the accession numbers EU805500 to EU805506.

[Structure of the glial cells in the nervous system of parasitic and free-living flatworms].

This study is devoted to ultrastructural and immunosytochemical investigation of the nervous system in parasitic and free-living platyhelminthes to learn if glial cells exist in the nervous system of flatworms. We described the ultrastructure of different types of glial cells and the peculiarities of myelinization of gigantic axons; immunoreactivity to the S100b protein is revealed. Comparative analysis of the glia structure of annelids and platods is given; structural, functional, and evolutionary aspects of myelinization of gigantic axons, which are revealed in cestodes, are discussed.

[Relationship between activity of fibrinolysis, parameters of lipid spectrum and carbohydrate metabolism].

In this work analysis of results of a prospective populational cohort study "Stress and health in Russia" is presented. We included in the study inhabitants of Moscow randomly sampled from the population of men and women aged > or =55 years. Aim of the present work consisted in the study of relationship of activity of fibrinolysis and main parameters of the system of lipoproteines providing transport of lipids in blood serum and system controlling utilization of glucose by tissues. In dependence on fibrinolytic activity all examined persons were divided into 3 groups: with hypofibrinolysis (group 1, n=41.5%), with normofybrinolysis (group 2, n=41.9%), and hyperfibrinolysis (group 3, n=16.6%). In persons of group 1 low fibrinolytic activity and high level of fibrinogen were combined with atherogenic spectrum of blood serum lipids and elevated level of insulin at normal level of glucose. In patients of group 3 elevated fibrinolytic activity was combined with more favorable composition of blood lipids, lower levels of insulin and glucose and absence of obesity. At study of relation between fibrinoltic activity and a row of clinical states by the method of logistic regression a tendency to elevation of prevalence of myocardial infarction in persons with hypofibrinolysis was found while in persons with hyperfibrinolysis a significant lowering of prevalence of arterial hypertension, ischemic heart disease, and angina pectoris was observed.

[Determination of the cause of repetitive syncopal States with the help of registration of electrocardiogram at the background of provocative test].

A clinical case of repetitive syncopal states in an adolescent with episodes of significant asystoles lasting up to 32 s is presented. These episodes were detected only with the help of electrocardiogram registered during provocative test. Beyond provoking factors the child had signs of insignificant sinus node dysfunction which did not allow to designate the state of the patient as severe and prescribe adequate treatment. We consider this case as demonstration of necessity of provocative tests in conjunction with ECG monitoring in children with episodes of fainting (syncopal states).

[The medical social aspects of children population morbidity in rural area].

The results of study of the children population morbidity carried out in the rural districts of Vladimirskaya Oblast revealed that 30.77% of children are needed the additional diagnostics, 14.01%--the additional physiotherapy, 35.16%--the dental care, 66.87%--the medical social care, 36.32%--the health education. The increase of the need in medical social services by various specialists depending of the children age is noted. The children of first year of life is established the need in permanent monitoring by three specialists--pediatrist (76.19%), surgeon (9.52%) and neurologist (4.76%). In the senior age group (16-18 years old) the need covered all the specialists including therapist (36.21%), gastroenterologist (24.14%), endocrinologist (20.69%), obstetrician-gynecologist (18.18% of girls), neurologist and otolaryngologist (18.97%), ophthalmologist (15.52%), surgeon and orthopedist (8.62%), psychologist and psychotherapeutist (6.69%), cardiologist and nephrologist (3.45%), oncologist (1.72%). The elaborated measures permitted to decrease the pediatric morbidity in average on 6% during two years.

[Normal values of temporal parameters of ECG in children according to results of clinico-epidemiological study ECG-screening of children and adolescents in Russian federation].

In order to obtain reliable information about time-domain ECG parameters in Russian children and to analyse their links with physiological changes the Project "ECG screening of children and adolescents of the Russian Federation" was carried out in 2003-2008. Time domain ECG parameters were studied in the representative sample of 5387 healthy individuals aged 0 to 18 years. In each age group, lower and upper limits of the norm for heart rate (HR), P wave, PQ and QRS intervals were defined as 2nd and 98th percentiles of their distribution. The equivalent limits of QT interval duration were defined as its 5th and 95th percentiles. Relationship between time domain parameters of pediatric ECG and HR was analyzed as well as relationship of these parameters with sex and age. The most important differences from prior pediatric studies completed 30 years ago were obtained for the heart rate limits. Among children aged 0 to 3, there was a tendency toward lowering of age-specific lower limits and elevation of age-specific upper limits. At ages older than 3 years, there was a tendency toward lowering of both the upper and the lower limits of HR. The newly obtained 2nd percentiles of the heart rate were lower than the known lower limits in nearly all ages. This indicates the necessity for revision of criteria of bradicardia in children. The present study showed that 5th and 95th percentiles of QTc interval (Bazett's formula) varied between 340 ms and 465 ms and were not significantly dependent on children's age and only for ages under 13 also on sex. Results of the study allowed to build age-specific ranges of norm for the time domain ECG parameters presented in a tabular form.

[Frequencies of the DRB1, DQA1, DQB1 and TNFA alleles in immigrant population of West Siberia].

Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.

[The assessment of quality of prevention activities in rural area].

The quality of health education and prevention activities within the medical institutions in rural area is assessed by the patients as adequate on all hallmarks (3.30 points). The higher indicators are established in relation to the development of interpersonal interactions of medical staff and patients (3.42 points), regularity and continuity (3.41 points) and timeliness (3.38 points) of educational and training activities in the area of healthy life-style. The lower assessment was established for availability (3.29 points), effectiveness and achieved satisfaction of patients (both 3.28 points). The lowest indicator was established for sufficiency of implemented measures in the area of formation of sanitary skillfulness of inhabitants of district (3.07 points). The study permitted to establish that the inhabitants of rural area doesn't dispose the needed knowledge in the area of one's own health preservation and promotion. In addition to that, the inadequate health education activities of medical personnel of the area related to the population is noted.

[Metabolic peculiarities of dyslipoproteinemias unrelated to high level of blood cholesterol].

The aim of this study was to reveal whether atherogenic or nonatherogenic properties of dyslipoproteinemias (DLP) not related to high level of blood total cholesterol (C) and low density lipoprotein C (LDL C) are determined only by shifts in serum triglycerides (TG) and/or high density lipoprotein cholesterol (HDL C) levels, or by other lipoprotein system alterations, if any. Biochemical factors regulating both lipid and carbohydrate metabolism were analyzed in two subsamples of Moscow residents aged 55 years with DLP: "high TG and low HDL C" and "normal TG and high HDL C" in comparison with randomly selected subsample assumed as "normal". Specific biochemical indexes of atherogenicity of DLP "high TG and low HDL C" were found, namely: increased apo B/AI ratio; disturbed functional activity of HDL in promoting reverse cholesterol transport expressed as elevated apo AII/AI ratio, decreased apo AI and phospholipids (PL) levels, decreased ratios of C/apo AI and C/PL in HDL, and decreased cholesterol-accepting capacity of HDL. Moreover, while fasting glucose level in subjects from this group remained unchanged, their fasting insulin level and HOMA-IR index were increased. Thus, DLP "high TG and low HDL C" is characterized by some specific metabolic features underlying its involvement into pathogenesis of atherosclerosis and type 2 diabetes mellitus. On the other hand, differences in biochemical parameters of antiatherogenic DLP "normal TG and high HDL C" from random subsample appeared to be opposite to differences from random subsample found for DLP "high TG and low HDL C", being in line with the present concept about their role in determining the antiatherogenicity of this kind of DLP.

[Rehabilitation of children with the connective tissue dysplasia in sport clubs and fitness complexes].

40 children aged from 12 to 17 years have been observed. All the children have been divided into three groups. The first group consisted of children with mild severity of joint hypermobility. The second group, 12 children -with mild severity of joint hypermobility. The third group consisted of 10 healthy children, it was a control group. The article in describes in details complexes of exercises used in a complex treatment of children with joint hypermobility. The efficiency of these complexes was established. They strengthen locomotor apparatus and prevent the progression of joint hypermobility.