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Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2012.2.2-03 | Award Amount: 14.15M | Year: 2013

The primary goal of PREVIEW is to identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, both embracing European and overseas countries: 1) A multicentre, clinical randomized intervention trial with a total of 2,500 pre-diabetic participants, including children and adolescents, adults and elderly. The duration will be 3 years for the adults and elderly, and 2 years for the children and adolescents. 2) Large population studies using data from all age groups. Focus in both lines of evidence will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress and sleeping pattern as well as behavioural, environmental, cultural, and socioeconomic variables. PREVIEW will significantly increase our knowledge on how specific lifestyle factors can help preventing type-2 diabetes. Type-2 diabetes accounts for about 90% of all cases of diabetes, primarily caused by the worldwide obesity epidemic. Diabetes is a costly disease and according to WHO, the direct health care costs of diabetes range from 2.5% to 15% of annual national health care budgets. This worrying trend calls for action and a need for a variety of innovative approaches. PREVIEW aims to be such an innovative attempt including all necessary disciplines and stakeholders, who can contribute to developing new ways for the prevention of this wide-spread life-style related disease. The strategic impact of PREVIEW concerns the massive problems associated with the global diabesity epidemic (obesity and type-2 diabetes) and therefore includes partners from Europe (East, West, North and South) and Australia, New Zealand, and Canada. PREVIEW will thereby contribute to improving health over the life-span of the population in Europe as well as worldwide. Overall the public health and socio-economic impact of PREVIEW is expected to be very significant.

Vitcheva V.,Medical University-Sofia
Current Medicinal Chemistry | Year: 2012

Cocaine belongs to the group of psychostimulants and together with amphetamines has been recognized as one of the most significant examples of drug abuse. Cocaine abuse is due to intense feelings of euphoria, friendliness, empathy, and hyperactivity, which result from its potent inhibitory effects on presynaptic dopamine and noradrenaline re-uptake. Misuse of cocaine can induce severe toxic effects, including neurotoxicity, cardiotoxicity, hepatotoxicity. There are a number of data, both experimental and clinical, regarding its hepatotoxic effects, associated with lipid peroxidation-induced oxidative damage. The oxidative metabolism of cocaine to reactive oxygen species (ROS) like nitrogen peroxide and superoxide anion radicals are thought to be responsible for the cocaine associated liver injury. This review summarizes the present information on cocaine hepatic biotransformation and the possible role of its oxidative metabolism in cocaine-induced hepatic injury. © 2012 Bentham Science Publishers.

Popova E.,Medical University-Sofia
Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology | Year: 2014

Dopamine is the most abundant catecholamine in the vertebrate retina. Despite the description of retinal dopaminergic cells three decades ago, many aspects of their function in the retina remain unclear. There is no consensus among the authors about the stimulus conditions for dopamine release (darkness, steady or flickering light) as well as about its action upon the various types of retinal cells. Many contradictory results exist concerning the dopamine effect on the gross electrical activity of the retina [reflected in electroretinogram (ERG)] and the receptors involved in its action. This review summarized current knowledge about the types of the dopaminergic neurons and receptors in the retina as well as the effects of dopamine receptor agonists and antagonists on the light responses of photoreceptors, horizontal and bipolar cells in both nonmammalian and mammalian retina. Special focus of interest concerns their effects upon the diffuse ERG as a useful tool for assessment of the overall function of the distal retina. An attempt is made to reveal some differences between the dopamine actions upon the activity of the ON versus OFF channel in the distal retina. The author has included her own results demonstrating such differences. © 2014 Springer-Verlag Berlin Heidelberg.

The effects of dopamine receptor blockade by sulpiride (D2-class antagonist) and sulpiride plus SCH 23390 (D1-class antagonist) on the V - log I function of the electroretinographic (ERG) b- and d-waves were investigated in light-adapted frog eyes. Sulpiride significantly decreased the absolute sensitivity of the b- and d-waves. The amplitude of the both waves was diminished over the whole intensity range studied. A similar effect on the b-, but not d-wave amplitude was seen during the perfusion with sulpiride plus SCH 23390. The effect on the d-wave amplitude depended on stimulus intensity. The threshold of the d-wave was not significantly altered. The suprathreshold d-wave amplitude was enhanced at the lower stimulus intensities and remained unchanged at the higher ones. The results obtained indicate that the action of endogenous dopamine on the photopic ERG shows clear ON-OFF asymmetry. Participation of different classes of dopamine receptors is probably responsible for this difference. © 2013 Springer-Verlag Wien.

Kamenov Z.A.,Medical University-Sofia
Experimental and Clinical Endocrinology and Diabetes | Year: 2015

Erectile dysfunction (ED) is more common in men with diabetes (DM). Dependent on the selected population, age, DM type and duration, the prevalence of diabetic ED (DED) varies from 32 to 90%. In 12-30% of men ED is the first sign of diabetes, diagnosed later. Today men with diabetes live longer than ever, and develop more late diabetic complications. Having in mind also the global ageing of the world population all this data suggests an increasing number of men with DED in the future. The main factors playing in the complex pathogenesis of DED are diabetic neuropathy (oxidative stress, polyol pathway, advanced glycation end-products, nerve growth factor deficiency, dysfunction of protein kinase C, tissue remodeling, etc.), macrovascular arterial disease (endothelial dysfunction, abnormal collagen deposition and smooth muscle degeneration, dyslipidemia, arterial hypertension, veno-occlusive dysfunction, etc.), hypogonadism, structural remodeling of the corporeal tissue, psychogenic components and adverse drug reactions. The diagnostic process is based on the results of questionnaires, neurological, vascular (Doppler) and other more rarely used investigations. Because of the complex pathogenesis of DED diabetic men represent a difficult treatment group. The difficulties are from the beginning, because patients do not talk about their problem spontaneously, and doctors do not ask about it. The treatment of DED should be team work, preferably including also specialists in sexual medicine. Psychological support and counseling of the couple is necessary in most cases. The general measures include implementation of a healthier lifestyle, improved glycemic-, lipids-, and arterial pressure control, and careful re-evaluation of the concomitant medications. The specific treatment includes as first line therapy the inhibitors of phosphodiesterase type 5 (PDE-5) with lesser effectiveness compared to non-DM men. There are rare studies with selected diabetic populations and even less with head-to-head comparisons between the PDE-5 inhibitors. Men with DM have a higher prevalence of hypogonadism. Testosterone replacement therapy should be started in symptomatic men with proven hypogonadism and no contraindications. Vacuum constriction devices and intracavernous or intraurethral applications of vasoactive drugs are the second line therapy. Vascular surgery rarely comes into consideration. The penile implant is the last and effective option in men with severe DED. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

STUDY DESIGN.: Randomized prevention trial. OBJECTIVE.: To compare the long-term effect of strengthening versus flexibility exercises and to evaluate the additional effect of abdominal bracing in recurrent low back pain ( LBP). SUMMARY OF BACKGROUND DATA.: No conclusions could be made regarding appropriate exercise types or parameters in recurrent LBP. Abdominal bracing increases trunk stiffness; however, its long-term effect has not been evaluated in recurrent LBP yet. METHODS.: Six hundred patients with recurrent LBP participated. They were randomized into 4 groups-150 patients ( age: 42.5 ± 12.7) performed strengthening exercises; 150 patients ( age: 41.3 ± 11.5) performed flexibility exercises; 150 patients ( age: 41.0 ± 13.2) performed strengthening exercises and used abdominal bracing in daily activities/ exercises; and 150 patients ( age: 40.6 ± 12.3) performed flexibility exercises and used abdominal bracing in daily activities/exercises. At the beginning of the study and at the end of 10 consecutive years were recorded 6 outcomes-frequency, intensity, and duration of pain, as well as frequency, intensity, and duration of exercises. RESULTS.: Regarding the first 4 outcomes-all groups showed improvement from the beginning to the second year, but worsening from the second to the 10th year; there was no difference between strengthening and flexibility groups; bracing groups showed better results versus nonbracing groups. Intensity, frequency, and duration of the pain correlated with each other and with frequency of the exercises, but not with exercise duration or intensity. CONCLUSION.: The exercise frequency is more important than the type, duration, or intensity of the exercise. Abdominal bracing adds to the exercise effect. It could be considered as a "preliminary muscle back belt on demand" increasing the trunk stiffness and the frequency of the trunk muscle contractions/cocontractions without interruption of daily activities, which may remind/convince the patients to exercise more frequently. Frequent exercising and bracing seems effective long-term prevention advices in recurrent LBP. © 2014, Lippincott Williams and Wilkins.

EVALUATION OF: Tan S, Noto JM, Romero-Gallo J, Peek RM Jr, Amieva MR. Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface. PLoS Pathog. 7(5), E1002050 (2011). The effects of Helicobacter pylori virulence factors on gastric epithelial cells are topics open to many studies. Major virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin (VacA), predict severe infection outcomes in many countries. H. pylori possesses various proteins for iron transport/storage, however, mechanisms of iron acquisition are not fully evaluated. The study by Tan et al. reveals a concurrent CagA/VacA activity for micronutrient acquisition and host tissue colonization. The virulence factors possess new activities, involving VacA-induced apical mislocalization of transferrin receptors to regions of H. pylori attachment and effects of both factors on polarized uptake and recycling of transferrin. The authors used many in vitro methods and an animal model. Iron acquisition by CagA was proven in vitro and in vivo by strain colonization of the gastric mucosa in iron-depleted conditions. CagA EPIYA motifs were associated with increased host internalization of transferrin. Importantly, CagA and VacA were involved in iron acquisition and colonization without severely damaging the host cells, thus favoring the infection chronicity. Further studies should assess molecular mechanisms of H. pylori iron acquisition, comparative activities of contact-dependent/soluble VacA and Eastern/Western CagA on the polarized epithelium and long-term effects of iron deficiency by virulent versus less virulent H. pylori strains. An interesting topic is the association of virulent strains with iron deficiency anemia but also with various H. pylori-induced diseases, in different populations and, possibly, for other bacterial infections. In conclusion, H. pylori iron acquisition is multifaceted. CagA and VacA work concurrently to provide both iron acquisition from interstitial holotransferrin and enhanced bacterial colonization of host cells apically. The new activities of the major virulence factors of adherent H. pylori are important both to research and in a clinical setting.

Popov T.A.,Medical University-Sofia
Annals of Allergy, Asthma and Immunology | Year: 2011

Objective: To review the fast-developing topic of assessment of exhaled breath components to improve the diagnosis and monitoring of respiratory and systemic diseases. Data Sources: Review of the literature available in monographs and journals. Study Selection: Articles and overviews on the broad spectrum of existing experimental and routinely applied methods to assess different aspects of human exhaled breath analysis were selected for presentation in this review. Results: Exhaled breath constitutes more than 3,500 components, the bulk of which are volatile organic compounds in miniature quantities. Many of these characterize the functioning of the organism as a whole (systemic biomarkers), but some are related to processes taking place in the respiratory system and the airways in particular (lung biomarkers). Assessment of lung biomarkers has proven useful in airway inflammatory diseases. It involves direct measurement of gases such as nitric oxide and inflammatory indicators in exhaled breath condensate such as oxidative stress markers (eg, hydrogen peroxide and isoprostanes), nitric oxide derivatives (eg, nitrate and nitrates), arachidonic acid metabolites (eg, prostanoids, leukotrienes, and epoxides), adenosine, and cytokines. Integral approaches have also been suggested, such as exhaled breath temperature measurement and devices of the "electronic nose" type, which enable the capture of approaches have also been suggested, such as exhaled breath temperature measurementexhaled molecular fingerprints (breath prints). Technical factors related to standardization of the different techniques need to be resolved to reach the stage of routine applicability. Conclusions: Examination of exhaled breath has the potential to change the existing routine approaches in human medicine. The rapidly developing new analytical and computer technologies along with novel, unorthodox ideas are prerequisites for future advances in this field. © 2011 American College of Allergy, Asthma & Immunology.

Patronov A.,Medical University-Sofia | Doytchinova I.,Medical University-Sofia
Open Biology | Year: 2013

Vaccination is generally considered to be the most effective method of preventing infectious diseases. All vaccinations work by presenting a foreign antigen to the immune system in order to evoke an immune response. The active agent of a vaccine may be intact but inactivated ('attenuated') forms of the causative pathogens (bacteria or viruses), or purified components of the pathogen that have been found to be highly immunogenic. The increased understanding of antigen recognition at molecular level has resulted in the development of rationally designed peptide vaccines. The concept of peptide vaccines is based on identification and chemical synthesis of B-cell and T-cell epitopes which are immunodominant and can induce specific immune responses. The accelerating growth of bioinformatics techniques and applications along with the substantial amount of experimental data has given rise to a new field, called immunoinformatics. Immunoinformatics is a branch of bioinformatics dealing with in silico analysis and modelling of immunological data and problems. Different sequence- and structure-based immunoinformatics methods are reviewed in the paper. © 2013 The Authors.

Zhivkova Z.D.,Medical University-Sofia
Current Pharmaceutical Design | Year: 2015

Human serum albumin (HSA) is the major plasma protein with vital functions acting as depot and career for many endogenous (fatty acids, bilirubin, etc.) and exogenous substances (drugs, nutrients, etc.) in the blood. Binding to HSA controls the free, active concentration of the drug and may affect considerably the overall pharmacodynamic and pharmacokinetic profile. Studies on drug – protein binding are important from both theoretical and practical point of view as they allow better understanding of the processes underlying drug disposition and elimination and the effect of several pathological states or co-administered drugs on drug delivery and efficacy. The present review focuses on the current state of drug – HSA binding studies. The major functions and consequences of drug – protein binding are described. The X-ray structure of HSA is discussed focusing on the location and the architecture of the primary drug and fatty acids binding sites. Some of the most commonly used methods for drug – HSA binding assay are presented together with examples for their application. The most extensive studied topics in the area are discussed including quantitative characterization of drug – HSA complexation, identification of the binding sites, stereoselectivity of drug – HSA interactions, and thermodynamic characterization of the binding process. A short section is devoted to in silico prediction of drug – HSA binding as an important step in drug design and development. © 2015 Bentham Science Publishers.

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