ANALYSING THE FINANCIAL VARIABLES OF BULGARIAN MUNICIPALITIES FOR THE PURPOSE OF THEIR FINANCIAL RECOVERY

Some of the latest supplements to the Public Finance Act deal with the local management of public funds and activities and prescribe a procedure for identifying municipalities in a financial difficulty and adopting measures to overcome it. This paper presents a set of methods for analysing the financial variables of individual municipalities on the basis of the methodological guidelines and the information provided by the Ministry of Finance. We have analysed data available as of the end of 2015 about the financial variables of Bulgarian municipalities as they have been defined by legislation and identified some common problems related to the financial management of that segment of the public sector

Metabolomic and Proteomic Analysis of the Mesenchymal Stem Cells’ Secretome

Mesenchymal stem cells (MSCs) are multipotent stromal cells with a strong potential in human regenerative medicine due to their ability to renew themselves and differentiate into various specialized cell types under certain physiological or experimental conditions. MSCs secrete a broad spectrum of autocrine and paracrine factors (MSCs’ secretome) that could exert significant effects on cells in their vicinity. MSCs have been clinically tested and have displayed a great potential in the treatment of bone/cartilage fractures and disorders, diabetes, cardiovascular diseases and immune, neurodegenerative and inflammatory diseases. The therapeutic efficacy of MSCs was initially attributed to their multipotent character and ability to engraft and differentiate at the site of injury. However, in recent years, it has been revealed that either undifferentiated or differentiated MSCs’ secretome plays an important role in the therapeutic potential of MSCs. The deciphering of the composition of MSCs’ secretome through proteomic and metabolic analyses and implementation of certain advanced analytical (nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), chromatography, etc.) and immunological methods could contribute to the understanding of the mechanisms underlying the therapeutic effects of MSCs

Sinteza, spektroskopska karakterizacija i ab initio istraživanje tioanaloga spirohidantoina

Dithioanalogues of cycloalkanespiro-5-hydantoins were prepared by reaction of the respective spirohydantoins with Lawesson’s reagent or P4S10. Cycloalkanespiro-5-(2-thiohydantoins) and cycloalkanespiro-5-(4-hydantoins) were also synthesized from cycloalkanespiro-5-(2,4-dithiohydantoins) via different reaction pathways. The structures of the compounds obtained were verified by 1H, 13C NMR and IR spectroscopy. Quantum-chemical calculations at the ab initio level of molecular nonlinear characteristics were performed. Increase of polarizability α and the second hyperpolarizability γ with enlarging the saturated ring was observed in all the structures studied.Ditioanalozi cikloalkan-spiro-5-hidantoina pripravljeni su reakcijama odgovarajućih spirohidantoina i Lawesson-ovoga reagensa ili P4S10. Sintetizirani su i cikloalkan-spiro-5-(2-tiohidantoini) i cikloalkan-spiro-5- -(4-tiohidantoini), uporabom različitih reakcijskih putova. Strukture dobivenih spojeva potvrđene su 1H, 13C NMR i IR spektroskopijom. Nelinearne molekularne karakteristike predviđene su kvantno-kemijskim računima na ab initio razini. U svim proučavanim strukturama, s povećanjem zasićenog prstena došlo je do porasta polarizabilnosti α i druge hiperpolarizabilnosti γ

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T-1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer

MSCs Conditioned Media and Umbilical Cord Blood Plasma Metabolomics and Composition.

Human mesenchymal stem cells (hMSCs) from umbilical cord (UC) blood (UCB) and matrix are tested clinically for a variety of pathologies but in vitro expansion using culture media containing fetal bovine serum (FBS) is essential to achieve appropriate cell numbers for clinical use. Human UCB plasma (hUCBP) can be used as a supplement for hMSCs culture, since UCB is rich in soluble growth factors and due to worldwide increased number of cryopreserved UCB units in public and private banks, without the disadvantages listed for FBS. On the other hand, the culture media enriched in growth factors produced by these hMSCs in expansion (Conditioned medium--CM) can be an alternative to hMSCs application. The CM of the hMSCs from the UC might be a better therapeutic option compared to cell transplantation, as it can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo- or xeno-transplanted cells. These facts drove us to know the detailed composition of the hUCBP and CM, by 1H-NMR and Multiplexing LASER Bead Technology. hUCBP is an adequate alternative for the FBS and the CM and hUCBP are important sources of growth factors, which can be used in MSCs-based therapies. Some of the major proliferative, chemotactic and immunomodulatory soluble factors (TGF-β, G-CSF, GM-CSF, MCP-1, IL-6, IL-8) were detected in high concentrations in CM and even higher in hUCBP. The results from 1H-NMR spectroscopic analysis of CM endorsed a better understanding of hMSCs metabolism during in vitro culture, and the relative composition of several metabolites present in CM and hUCBP was obtained. The data reinforces the potential use of hUCBP and CM in tissue regeneration and focus the possible use of hUCBP as a substitute for the FBS used in hMSCs in vitro culture

Risk Of Development Of Solid Tumors In Patients With Systemic Lupus Erythematosus

Системният лупус еритематозус (СЛЕ) е автоимунно заболяване, характеризиращо се с продуциране на различни автоантитела, активиране на комплемента и отлагане на имунни комплекси. Връзката между СЛЕ и рака отдавна е установена. При пациенти със СЛЕ честотата и рискът от злокачествено заболяване се увеличава за белодробен карцином, рак на шийката на матката, хепатоцелуларен карцином и др. В същото време честотата на карцином на гърдата, на простатната жлеза и яйчниците е ниска в редица проучвания на СЛЕ пациенти.Известни са редица фактори, които могат да допринесат за развитието на злокачествени заболявания при СЛЕ. В този преглед ние представяме някои по-често срещани солидни тумори и тяхната честота при пациенти със СЛЕ, както и факторите, които влияят на туморогенезата в условията на автоимунно заболяване.Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by production of different autoantibodies, complement activation, and immune complex deposition. An association between SLE and cancer has long been known. In patients with SLE, the incidence and risk of overall malignancy is increased for lung cancer, cervical cancer, liver cancer, and etc. Conversely, the incidences of prostate, breast and ovarial cancers are decreased in a number of studies of SLE patients.There are many factors, which can contribute to the development of malignancies in SLE. In this review we present some more common solid tumors and their incidence in SLE patients as well as the factors that affect tumorigenesis in conditions of autoimmune disease

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL-1 ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.info:eu-repo/semantics/publishedVersio

Leptospirosis in elderly patients

Leptospirosis is a re-emerging zoonosis with broad clinical spectrum and high mortality in severe forms. The aim of this study was to analyze clinical manifestations, laboratory findings, epidemiological data, and management in elderly patients with leptospirosis. Toward that end, we performed a descriptive analysis of 15 leptospirosis elderly cases (age 60-78 years) treated at the Clinic of Infectious Diseases of University Hospital - Pleven (1976-2012). Patients were serologically confirmed by microscopic agglutination test. Twelve cases (80%) presented with the severe form of leptospirosis. Co-morbidity (hypertonic diseases, chronic pulmonary diseases, chronic alcohol abuse, and diabetes) was registered in 13 cases. All cases had fever, oliguria, conjunctival suffusions, hepatosplenomegaly. Jaundice (14/93%), hemorrhagic diathesis (13/87%), vomiting (11/73%), abdominal pain (10/67%), myalgia (7/47%) and hypotension (7/47%) also were observed. Renal dysfunction was expressed by increased blood urea nitrogen (mean 38.1 ± 24.1 mmol/L) and serum creatinine (mean 347.6 ± 179.8 µmol/L). Hepatic dysfunction was expressed by increased total serum bilirubin level (mean 274.6 ± 210.7 µmol/L) and slightly elevated aminotransferases (ASAT mean 125.8 ± 61.6 IU/L; ALAT mean 131.3 ± 126.5 IU/L). Five cases (33%) had a lethal outcome. In conclusion, leptospirosis in elderly patients is associated with severe course and higher risk for death, and requires prompt intensive treatment

Artemisia Annua- a Plant with a Great Future

Introduction: Artemisia annua is a common type of sweet wormwood, an herb employed in Chinese traditional medicine and introduced throughout the world. It belongs to the family of Asteraceae and has fern-like leaves, a camphor-like scent and bright yellow flowers . The glandular structures found on their surface produce a wide range of bioactive compounds and contain the chemical artemisinin. Its remarkable properties are the key to its malaria- and cancer-fighting effects.Materials and Methods: For our research we used a wide spectrum of sources including many medical articles, books, encyclopedias and well-known medical journals  and, of course, the information and the knowledge of our academic mentor.Results: This study goes through the main stages of pharmacological development  of artemisinin including the discovery of its effects and mechanisms of action. We present shortly the well-known effect on malaria and explain in details the most recent studies proving artemisinin`s anti-cancer effects. In short, cancer cells tend to express high levels of the transferrin receptors for internalizing iron which is a useful difference from normal cells along with the difference in the iron transport and this is the reason why artemisinin compounds kill only cancer cells and spare normal ones.Conclusion: In conclusion artemisinin, like many marvels of modern medicine, has been discovered by accident but series of experimental studies show that artemisinin is highly effective against a variety of cancers. Leukemia and colon cancer are the two types where its influence is most widely explored.  The result from our study, we believe, would inform the audience about the latest scientific discoveries in the field, which is in any case  beneficial