Spectroscopic, zeta potential and molecular dynamics studies of the interaction of antimicrobial peptides with model bacterial membrane.

Peptide-membrane interactions play a key role in the mechanisms of activity of antimicrobial peptides. Here, methods of fluorescence spectroscopy, zeta potential, and molecular dynamics modeling were used to study the interaction of new antimicrobial peptide megin with model bacterial membrane. The Gibbs free energy of -6 kcal/mol characterizes the interaction of the peptides with liposomes containing DOPE and POPG lipids. Fluorescence data, acrylamide quenching, and MD simulations show that megin peptides are mainly located at the lipid/water interface and are aligned parallel to the bilayer surface in a carpet like manner. Measurements of zeta potential demonstrate the decrease of the negative potential of liposomes in the presence of peptides. The influence of megin on the membrane properties is also confirmed by molecular dynamics simulations. Insertion of peptides into the membrane disturbs lipid ordering, decreases the order parameters of lipids, and facilitates penetration of water molecules through the membrane. According to our results, we proposed that the megin antimicrobial activity can be explained by the carpet model of peptide activity.

[The Effect of Bromocriptine on Clinical and Laboratory Parameters in Patients With Peripartum Cardiomyopathy].

Aim      To evaluate the effect of bromocriptine on clinical hemodynamic and functional indexes and to analyze life prognosis for patients with periportal cardiomyopathy divided into two groups: group 1, bromocriptine treatment (n=21) and group 2, standard treatment without bromocriptine (n=22). History was taken, examination and standard clinical evaluation were performed, the Clinical Condition Scale (CCS with V.Yu. Mareev, 2000, modification) was administered, and 6-min walk test (6MWT) was performed. Quality of life was determined with the Minnesota questionnaire. Standard 12-lead electrocardiography, echocardiography, and blood biochemistry with measuring C-reactive protein (CRP) and prolactin, were performed. Follow-up duration was one year.Results Heart rate was significantly decreased in group 1 (22.7%) compared to group 2 (18%); the 6-min distance was increased (61 and 50 %, respectively), the total CCS score was decreased (66 and 55 %, respectively, and the quality of life Minnesota questionnaire score was improved (from 68.4±12.4 to 26.4±12.4 and from 63.4±10.9 to 36.4±15.1, respectively). Also, left ventricular (LV) end-diastolic dimension was reduced from 66.82±7.07 to 60.67±3.79 mm (9.2 %) in group 1 and from 61.92±4.41 to 58.91±4.68 mm (5 %) in group 2, which was associated with increases in LV ejection fraction by 18.3 and 14.5 %, respectively. In both groups, CRP concentration was decreased from 8.3±4.1 to 4.3±1.2 mg/l and from 8.5±3.5 to 6.3±1.5 mg/l, respectively. The bromocriptine treatment was associated with a significant decrease in prolactin level (62 %). The LV function completely recovered in 66.6% of patients in group 1 and in 27% of patients in group 2.Conclusion      The bromocriptine treatment of periportal cardiomyopathy in combination with an optimal drug therapy was associated with an additional beneficial effect on the clinical functional status, intracardiac hemodynamics, blood concentration of CRP, and a potentiality for complete recovery of the LV function.

PRO-INFLAMMATORY EFFECTS OF EXPERIMENTAL HYPERTHYROIDISM IN COLON OF MICE (IMMUNOHISTOCYTOCHEMICAL STUDY).

Thyroid hormones can exert responses in various immune cells affecting several inflammation-related processes. The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions. Aim of study - to answer the question if hyper- or/and hypothyroid state can be as provoking factor for inflammation in colon. The study was performed on 60 mature male mice of the inbred line C3H-A. On male mice was reproduced a model of experimental hyperthyroidism and hypothyroidism by oral intake of L-thyroxin and propylthyouracil, accordingly. By the 22nd week of the experiment all animals were sacrificed. The rectum was removed for histo- and immunocytochemical examination. In histological examination in hyperthyroid group the hypertrophy of the mucous membrane of the colon is detected. Simultaneously the frequency of cell mitosis is increased. Among the epithelium glands of the colon can clearly be seen apoptotic bodies. Moderate or expressed infiltration by lymphocytes and plasma cells is elucidated in mucous membrane of colon relatively to mucous membrane of colon of euthyroid group i.e. control one. In hyporthyroid group the hyportrophy of the mucous membrane of the colon was detected. The lymphocytic infiltration is not found. In immunocytochemical examination the frequency of CD20 and CD56 positive cells was significantly higher (>23%) in cytological preparation of membrane mucous of colon from hyperthyroid mice (p<0.01). Meanwhile CD20 and CD56 positive cells were detected in single cases in cytological preparation of membrane mucous of colon from hypothyroid mice. The same observation was done for healthy membrane mucous from control (euthyroid) group. It is possible that the thyroid status is one of the factors modulating the inflammation. This discussion is far from over, because it is unclear whether prolonged hyperthyroidism can actually activate pro-inflammatory reactions, which subsequently, in turn, activate carcinogenesis.

OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE.

Corticoliberin (CRF) isn't only regulates hypothalamic-pituitary-adrenal axis activity, but also functions as a neurotransmitter in extrahypothalamic brain regions like amygdala, implicated in the emotional responses to stress. The CRF system provides an input to orexin neurons and can modulate the activity of orexinergic neurons in stress response. Some data showed the role of orexin-A in extinction of aversive memory. The orexin system was shown to participate in stress-induced behavior connected with the extended amygdala structures, like central nucleus of the amygdala. The objective was to study the effects of orexin-A antagonist SB-408124 in rats after predator-induced stress using behavioral tests and its effects on CRF level in amygdala. In this study 30 male Wistar rats were used. The animals received an intranasally selective antagonist of Orexin receptor 1 type SB-408124. Posttraumatic stress disorder was modelled by single predator exposure. A group of 10-12 rats were placed in a terrarium with an indian python. 7 days after exposure to the predator, the behavior of animals was tested in the Open Field and Elevated Cross-Maze tests. Free motor activity of animals was studied in the "open field" test. To assess stress, we used the "elevated cross-maze " test. CRF concentrations in brain structures were measured by solid-phase ELISA using the Corticotropin Releasing Factor (CRF) test system. In the group of stressed rats receiving intranasally SB-408124, the time of stay in the light arm was restored, but did not reach the control values, the number of runs was restored to the control level, and the number of grooming acts increased in comparison with both the control group and the stressed animals. In the "open field" in the group of stressed rats receiving saline solution, the number of sniffs and rearing were decreased, but the number of peeks into holes was increased. In the group of stressed rats receiving SB-408124 20 µg intranasally, the number of sniffs was increased and the number of hole peeking decreased in comparison with the stressed rats receiving saline solution. The CRF level in the homogenates of amygdala in stressed rats was lower (0.44±0.07 ng/mg protein vs. 0.61±0.01 ng/mg in the control group). In the intranasal administration of SB408124 group this decrease was not recorded and the CRF level in the amygdala was 0.57±0.01 pg/mg protein. Orexin A antagonist SB-408124 reduced anxiety after psychotraumatic exposure. Predator induced acute psychotraumatic exposure decrease CRF level in the rat's amygdala. Intranasal administration of selective orexin 1 receptor antagonist SB408124 restored it closely to normal and has an anxiolytic effect on animal behaviour.

UNEQUAL HORMONAL RESPONSE OF MALE AND FEMALE C3H-A MICE TO THE THYROID AND ANTITHYROID AGENT TREATMENTS.

The state of physiological functions of the whole organism, its vital activity and adaptation to various changes in the surrounding and internal environment is controlled by neurohumoral mechanisms. The main place in the implementation of those mechanisms belongs to hormones. A clinically relevant problem is currently the relationship between activity of thyroid gland and prolactin. Aim of study. - To elucidate further the relationship of thyroid-stimulating hormone, thyroxine and prolactin. The study was performed on virgin 30 mature male mice and 33 mature female mice of the inbred line C3H-A. On male and female mice was reproduced a model of experimental hyperthyroid and hypothyroid status by the administration to L-thyroxin and propylthyouracil, accordingly. The blood samples from animals were assayed for TSH, T4 (total) and prolactin. In the hyperthyroid male mice the level of T4 (total) was significantly higher as compared to the hypothyroid and control groups. No deference for the level of TSH and prolactin was found between the hyperthyroid and the hypothyroid groups. In the hypothyroid female mice the level of TSH and T4 (total) was significantly lower and the level of prolactin was significantly higher as compared to the hyperthyroid and the control groups. The male and female mice responded in different ways upon the administration to L-thyroxin and propylthyouracil on the level of TSH, T4 (total) and prolactin.

[Characteristic of circulating immune complexes in the blood of children with asthma].

Circulating immune complexes (CIC), which are heterogeneous in size and composition population of antibodies and antigens, are critical mediators of the immune system. Precipitation of the CIC on the vascular wall and basal cell membranes causes a variety of biological effects: activation of the complement system in accordance with the classical pathway, activation of macrophages initiating the development of a local inflammatory process involving mast cells and neutrophils. In the present study, we have examined the content and physical characteristics of the CIC in the serum of children with atopic asthma and healthy individuals. We have found that the concentration of CIC in patients is 2-fold higher than in control group. The presence of the most pathogenic medium-sized complexes was determined in 9% of healthy children and 85.6% of children with asthma.

[Specific features of the clinical picture and course of familial dilated cardiomyopathy].

AIM: To study prevalence, clinical and hemodynamic features, and life prognosis in patients with familial dilated cardiomyopathy (DCM). SUBJECTS AND METHODS: Two hundred and forty-four patients with DCM were examined during the period 2000 to 2010. According to their medical history records and the results of clinical and functional studies, familial cardiomyopathy was diagnosed in 29 (11.8%) of 244 patients. For comparative assessment, the authors formed two groups: 1) 29 patients with the familial form of DCM and 2) 83 patients with its sporadic form. Their examination included ECG, Holter ECG monitoring, 6-minute walk test, X-ray cardiometry, coronarography, and life prognosis assessment. RESULTS: It has been established that the prevalence of the familial form of DCM accounts for 11.9% and is, unlike its non-familial form, associated with younger age; it is maternally inherited in one third of cases and characterized by the development of complete atrioventricular block in some patients. CONCLUSION: Investigating the life prognosis of the patients has shown that the familial form and age less than 30 years are characterized by a rapidly progressing course accompanied by a significant increase in death rates within the first 12 follow-up months.

[Periportal cardiomyopathy. Some peculiarities of clinical picture and course of the disease].

Results of the study of special characteristics of the course of chronic heart failure (CHF) in women with periportal cardiomyopathy (PCMP) are presented. We have found that prevalence of PCMP in the structure of dilated cardiomyopathy is 9.5%. PCMP compared with idiopathic cardiomyopathy is characterized by less pronounced dilation of left cardiac chambers, relative preservation of left ventricular contractile function, more favorable course of CHF with lower frequency of destabilizations of clinical state. PCMP has developed mainly during postportal period and in women with preexisting anemia and chronic viral diseases.

Carboxyangiography: a new type of opacification in angiographic practice--first clinical experience.

The study was undertaken to investigate a possibility of clinical application of medical-purpose CO2 as an alternative radiopaque agent (RA) for visualization of major arteries and veins. During the period from April 2009 to June 2010, a total of fifty 38-to-72-year-old patients (mean age 58 years) underwent angiographic examinations wherein medical-purpose CO2 was employed as a radiopaque agent. We performed 39 aorto-arteriographies, 10 portographies, and one mesentericography. Medical carbon dioxide used for vascular opacification makes it possible to obtain high-quality images of the vascular bed and is sometimes even superior to water-soluble RAs.

[Effects of atorvastatin and acipimox on the lipid spectrum of blood plasma, endothelial function and a clinical course of unstable angina pectoris].

AIM: Assessment of effects of a 3-month course of atorvastatin and a nicotinic acid derivative acipimox on the lipid spectrum, platelet aggregation, results of brachial artery reactive hyperemia test and clinical outcomes in patients with unstable angina pectoris (UAP). MATERIAL AND METHODS: A total of 109 males with new-onset and progressive UAP entered the trial. They had LDLP cholesterol > or = 115 mg/dl. RESULTS: The addition of atorvastatin to combined therapy of UAP patients resulted in achievement of a target level of LDLP cholesterol level in 64% dose-adjusted patients while in acipimox patients the target level was achieved in 20% patients. In spite of a more potent effect on endothelial function, acipimox had an insignificant effect on the treatment outcomes. CONCLUSION: Hypolipidemic therapy with atorvastatin and acipimox for UAP leads to a significant reduction in LDLP cholesterol. The effect of atorvastatin comes much earlier and more frequently provides a target level of LDLP cholesterol.

[Humoral markers of endothelial dysfunction in essential hypertension]. / Gumoral'nye markery disfunktsii éndoteliia pri éssentsial'noi gipertonii.

AIM: To elucidate potential markers of endothelial dysfunction and relationships between humoral and vasoregulatory responses of the endothelium in patients with essential hypertension. MATERIAL: Thirty four male patients (mean age 54.4+/-9.2) with I-II degree hypertension and left ventricular hypertrophy. METHODS: Endothelial function was assessed non-invasively by registration of flow-mediated brachial artery dilatation. Serum level of vascular adhesive molecule 1S (VCAM-1S) was measured by enzyme immunoassay, levels of aldosterone and insulin-like growth factor-1 (IGF-1) - by radioimmunoassay. RESULTS: Brachial artery flow mediated dilatation was 2.0+/-7.46%. Patients with hypertension compared with healthy subjects had significantly higher mean levels of VCAM-1S (713.9+/-123.2 and 590.8+/-51.8 pg/ml, respectively, p<0.001), aldosterone (105.41+/-50.17 and 42.7+/-13.16 ng/ml, respectively, p<0.001), and IGF (209.7+/-49.1 and 137+/-21 pg/ml, respectively, p<0.001). Direct significant correlations were found between humoral and functional markers of endothelial dysfunction in the group of patients with essential hypertension. CONCLUSION: These results can be interpreted as indicative of pathogenetic role of IGF-1 and aldosterone in the development of the endothelial dysfunction and myocardial remodeling in essential hypertension

[Genetic and epidemiological studies in Dagestan highland isolates]. / Genetiko-épidemiologicheskie issledovaniia v gornykh izoliatakh Dagestana.

Interpopulation differences in the epidemiology and age of onset of complex diseases, as well as expression of some vital parameters, have been found. The relationship between these interpopulation differences and the genetic processes that have been occurring in the populations throughout their history has been demonstrated. The Daghestan genetic isolates studied are characterized by aggregation of certain complex diseases. In each genetic isolate, almost all affected subjects with homogeneous clinical phenotypes belong to the same large pedigree with a limited number of founders. There is evidence for a large variance of the population risk of schizophrenia (morbid risk) in Daghestan isolates (this parameter varies from 0 to 5%). Examination of 211 cases of schizophrenia earlier diagnosed in Daghestan psychiatric hospitals has shown that only 139 of them meet the DSM-IV criteria for schizophrenia. The remaining 72 subjects have, according to DSM-IV criteria, various schizoaffective and affective disorders; all of these subjects are close relatives of the schizophrenic patients. The age of onset of schizophrenia in the isolates studied varies from 14 to 40 years (20.84 +/- 0.568 years). Offspring of consanguineous marriages exhibit later age at onset and a higher risk of schizophrenia than offspring of exogamous marriages. The results of multivariate genetic analysis indicate that different gene complexes are involved in the pathogeneses of early-onset and late-onset forms of schizophrenia. An association of schizophrenia incidence, its age dependence, and reproductive parameters with polymorphisms of some microsatellite loci have been demonstrated.

[Genetic subdivision of Dagestan ethnic populations]. / Geneticheskaia podrazdelennost' étnicheskikh populiatsii Dagestana.

Relationships between ethnic and genetic differentiation with respect to 54 microsatellites have been analyzed in five Daghestan ethnic groups. To detect the microsatellites, human chromosomes 3, 17, and 18 were screened with a step of 10 cM (Weber/CHLC 9.0 markers) at the Mammalian Genotyping Service (National Institute of Health, United States). Comparison of the polymorphism of these loci in Daghestan populations with average worldwide data has revealed generally low heterozygosity in Daghestan populations, which is accounted for by traditional endogamous and consanguineous marriages throughout the history of these populations. The inbreeding coefficient in Daghestan ethnic groups varies from 0.005 to 0.0134 and is close to the worldwide maximum known to date. For some DNA loci, significant differences between the offsprings of consanguineous and exogamous marriages with respect to allele sizes and their variance have been found. The Daghestan ethnic populations studied differ from one another in both the frequencies of common alleles and the presence of rare alleles that are unique for each ethnic group of Daghestan and have not been found in any other population in the world.

[Mapping genes of complex diseases in genetic isolates of Dagestan]. / Kartirovanie genov kompleksnykh zabolevanii v geneticheskikh izoliatakh Dagestana.

Original results of the analysis of genetic linkage between some genomic markers and two complex clinical phenotypes, schizophrenia and mental retardation, in pedigrees from Dagestan genetic isolates are described. Interpopulation differences in the epidemiology of the complex phenotypes were studied and in their genetic linkage was demonstrated. These differences are evidently related to the genetic structure of the isolates determined by their genetic history. The MR epidemiological index characterizing the lifetime morbid risk of schizophrenia varies in the Dagestan isolates studied from 0 to 4.95%, which is almost five times higher than the average worldwide population rate, 1%. Comparative genetic mapping permitted determination of the most probable genetic linkages and associations of loci from chromosomal regions 17p11.1-12, 3q13.3, and a locus from 22q with schizophrenia and locus 12q23 with mental retardation. There is evidence that this approach is effective for detailed study of the relationship between the genetic (allele and locus) and clinical heterogeneity of complex diseases, which favors successful identification of the genes determining them. The study of linkage disequilibrium (LD) in genetic isolates of Daghestan populations (which have a common genetic background) may be an effective methodological approach for revealing the numerous contradictory results of mapping of the same genes of complex disease performed by different researchers in different regions of the world.

The ascertainment of multiplex schizophrenia pedigrees from Daghestan genetic isolates (Northern Caucasus, Russia).

This article describes the preliminary ascertainment of multiplex schizophrenia pedigrees from the isolated mountain region of Daghestan (Northern Caucasus, Russia). Daghestan has a population of two million people and contains 26 aboriginal ethnic groups. Many of the ethnic groups reside in remote mountain villages that can be classified as 'primary isolates'. Prolonged reproductive isolation and severe environmental conditions in the highlands have created diverse, genetically isolated ethnic populations in Daghestan. A number of the isolates in this region contain large extended multiplex schizophrenia pedigrees that are ideal for genetic analyses. During summer expeditions of 1996 and 1997, 14 separate large multiplex schizophrenia pedigrees were ascertained from 14 different mountain villages. Of the 14 kindreds, one had 50 schizophrenic cases available for ascertainment, one had 32, and another had 24. Seven of the remaining pedigrees had between 11 and 23 living cases. Within the kindreds, the number of males with chronic schizophrenia was at least twice that of females. The average age of onset of schizophrenia is 21.2 years for offspring of consanguineous marriages and 17.4 years for offspring of nonconsanguineous marriages (P = 0.033). Although the pedigrees ascertained from the remote mountain villages may not be representative of the general population, they are unique kindreds for mapping schizophrenia susceptibility genes.

[Thrombocyte aggregation in patients with cardiac arrhythmias and effect of anti-arrhythmia agents]. / Agregatsionnaia aktivnost trombotsitov u bolnykh s narusheniiami ritma serdtsa i vliianie na neë antiaritmicheskikh preparatov.

Platelet aggregability was studied in 81 patients with prior myocardial infarction with various cardiac arrhythmias and its effects of some antiarrhythmic agents (allapinine, ethacizine, obsidan and cordarone). It was 32-39% higher in patients with frequent ventricular extrasystole (VE) and VE of high grades (4a and 4b by the classification of Lown and Wolt) than in control patients (without arrhythmias) and patients with supraventricular and rare VE. Ethacizine and cordarone produced a significant inhibitory effects on platelet functional activity, but the effects of allapinine and obsidan on this parameter were insignificant. There was no correlation between the magnitude of antiarrhythmic effects of the drugs and their antiaggregatory properties. It was shown that the results of examining the effects of antiarrhythmic agents on platelet aggregability in vitro were not in agreement with those obtained in vivo.

[Clinico-morphological characteristics of developmental defects of the eye]. / Kliniko-morfologicheskaia kharakteristika porokov razvitiia organa zreniia.

Analysis of the records of the ophthalmologic pathoanatomic laboratory of the Kazakh Research Institute of Ophthalmic Diseases has shown that the incidence of developmental abnormalities due to disorders in the embryonal period and organogenesis have made up 3.7 percent of the total number of ocular tumors and 6.0 percent of benign tumors over the past 34 years. More than 60 percent of the patients with developmental defects were residents of South-Eastern Kazakhstan, equally frequently aborigens and representatives of other nationalities (41 and 43 patients, respectively), with male patients predominating (46 of 84 subjects). The patients' ages varied from 3 months to 70 years, children under 14 (50 patients) and young subjects aged 14 to 30 (24) prevailing. The most frequent developmental defects were dermoid cysts (61.9 percent) localized mainly in the orbit, less frequently dermoids and lipo-dermoids (20.2 percent) in the cornea, and dystrophic lacrimal gland in scleral conjunctiva (14.3 percent). Teratoma, brain hernia, and cystic eyes occurred in 1.2% of cases each; these conditions and dystopic lacrimal gland were histologically diagnosed.

[Congenital pathology of the eye as a main cause of impaired vision in children]. / Vrozhdennaia patologiia organa zreniia kak osnovnaia prichina snizheniia zreniia u detei.

Congenital diseases of the eyes is the most frequent cause of vision reduction in children and one of the major causes of invalidity for poor sight. The aim of the present study was analysis of the causes of congenital ocular diseases in children in Kazakhstan. Results of prophylactic examinations at some rural districts of the republic evidence that refraction abnormalities rank first in the structure of congenital ocular diseases, oculomotor system abnormalities second, and defects of the eyelids and lacrimal tract, third. Congenital diseases of the eye make up 29-42 percent of all ocular diseases in children. Hospital records evidence a 45 percent incidence of congenital diseases of the eye. Lenticular abnormalities rank first, oculomotor system pathology second, and eyelid diseases third in the structure of congenital diseases of the eyes.