Erythromycin Series. X. Inhibitory Activity of Several New Erythromycin Derivatives in Cell-Free Amino Acid Polymerization Systems

Erythromycin A (I), erythromycin A 9-oxime (11), 9(S)-erythromycylamine (V), and several new derivatives of these compounds, were assayed for their ability to inhibit the poly(A)-directed synthesis of polylysine and the poly(C)-directed synthesis of polyproline in cell-free systems from Escherichia coli. The rate of polypeptide synthesis was inhibited 500/o by concentrations between 0.5 and 1.5 ~tmol · dm-3 of the eight examined compounds, in the following decreasing order of activity: methylsuccinate of V (VI), I, V, II, methylsuccinate of II (111), p-toluenesulfonyl-V (VII), p- acetylamino-benzenesulfonyl-V (VIII), and ethylsuccinate of I (IV). The derivative of VII lacking cladinose (IX) showed lower but still significant activity. Hence, none of the substitutions in the position 9 of the macrolide ring, present in these compounds, impairs the ability of I to bind the prokaryotic ribosome and inhibit its function, which is the basis for antibacterial activity of erythromycines

Mesenchymal Stem Cells from Periapical Lesions Upregulate the Production of Immunoregulatory Cytokines by Inflammatory Cells in Culture

The pathophysiology of periapical lesions (PLs) is under control of pro-inflammatory and anti-inflammatory (mainly immunoregulatory) cytokines. We have recently established mesenchymal stem cells (MSCs) from PLs and showed their suppressive effects on the production of proinflammatory cytokines from PLs inflammatory cells (ICs). In this work we studied the production of interleukin (IL)-10, IL-27 and transforming growth factor (TGF)-β, by PL-ICs in direct or indirect contacts with PL-MSCs. PL-ICs, which were isolated from four different asymptomatic PLs, predominantly composed of lymphocytes, followed by neutrophil granulocytes, macrophages and plasma cells. PLMSCs, expressing typical MSC markers, were co-cultivated with PL-ICs at 1:10 ratio, either in direct contact or in a transwell-system, for 24 hours. The levels of cytokines in cell-culture supernatants were tested by ELISA. The results showed that PL-MSCs up-regulated the production of all three immunoregulatory cytokines by PL-ICs. PL-MSCs stimulated the production of IL-10 and IL-27 via soluble factors, whereas the up-regulation of TGF-β required direct cell-to-cell contacts. In conclusion, our results showed for the first time the involvement of PL-MSCs in restriction of inflammation in PLs by up-regulation of immunoregulatory cytokines

Subjective element of a criminal offence in English law

Докторска дисертација под насловом „Субјективни елемент кривичног дела у енглеском праву“ за предмет има анализу питања кривице и с њом повезаних института у енглеском (англосаксонском) кривичном праву. Основни циљ који је истраживањем постављен је утврђивање начина на који је обликован један од најважнијих кривичноправних појмова у англосаксонској доктрини и у којој мери се англосаксонско учење разликује од владајућег схватања у земљама које припадају грчко-романско-германској правној традицији. Кривично право у Енглеској је, као и правила из области других грана права, пре свега спонтано створено у дуготрајном поступку судског одлучивања и традиционално је више окренуто процесноправним него материјалноправним правилима и институтима. Начин вођења кривичног поступка, уз значајно учешће лаичког елемента и начелна оријентисаност ка практичним питањима у покушају да се спор праведно разреши без претераног позивања на сложене теоријске конструкције, разлог су што је англосаксонска наука кривичног права на нижем ступњу догматског развоја у поређењу са евроконтиненталном кривичноправном мисли. Англосаксонско учење о кривици је концепцијски поједностављено и уклопљено је у оквире традиционално субјективистичког и психолошког учења. Иако се кривица сматра конститутивним елементом општег појма кривичног дела, њена структура је упрошћена (сведена је само на облике или степене кривице) и за разлику од евроконтиненталног схватања не обухвата елементе нормативне садржине (свест о противправности).The subject matter of a doctoral thesis titled „Subjective Element of a Criminal Offence in English Law” is the analysis of guilt and guilt-related legal institutes in English (Anglo-Saxon) criminal law. The main purpose of this research is to establish the manner in which one of most important criminal and legal concepts of the Anglo-Saxon law was formed and to which extent the Anglo-Saxon body of law differs from prevailing concepts in the countries influenced by the Greco – Roman – Germanic legal tradition. Criminal Law in England, as well as the rules from other branches of law, evolved in the first place spontaneously from a long lasting process of judicial decision making, and is traditionally more inclined toward procedural rather than toward substantive law rules and institutes. The manner of conducting a criminal proceedings with significant presence of layman’s terms, and general orientation towards practical issues in an attempt to justly resolve a dispute without ample referral to complex theoretical constructs, stand behind the fact that the Anglo-Saxon system of criminal jurisprudence is at a lower level of dogmatic development than the European-Continental system of criminal jurisprudence. The Anglo-Saxon concept of guilt is conceptually simplified and fits into the framework of traditional subjective and psychological learning. Despite the fact that guilt is considered a constitutive element of a general term of criminal offence, its structure is simplified (it is reduced only to the forms and degrees of guilt) and unlike the European- Continental understanding, it does not include the normative content (awareness of unlawfulness of the act)

Age-Related Differential Stimulation of Immune Response by Babesia microti and Borrelia burgdorferi During Acute Phase of Infection Affects Disease Severity

Lyme disease is the most prominent tick-borne disease with 300,000 cases estimated by CDC every year while ~2,000 cases of babesiosis occur per year in the United States. Simultaneous infection with Babesia microti and Borrelia burgdorferi are now the most common tick-transmitted coinfections in the U.S.A., and they are a serious health problem because coinfected patients show more intense and persisting disease symptoms. B. burgdorferi is an extracellular spirochete responsible for systemic Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Immune status and spleen health are important for resolution of babesiosis, which is more severe and even fatal in the elderly and splenectomized patients. Therefore, we investigated the effect of each pathogen on host immune response and consequently on severity of disease manifestations in both young, and 30 weeks old C3H mice. At the acute stage of infection, Th1 polarization in young mice spleen was associated with increased IFN-γ and TNF-α producing T cells and a high Tregs/Th17 ratio. Together, these changes could help in the resolution of both infections in young mice and also prevent fatality by B. microti infection as observed with WA-1 strain of Babesia. In older mature mice, Th2 polarization at acute phase of B. burgdorferi infection could play a more effective role in preventing Lyme disease symptoms. As a result, enhanced B. burgdorferi survival and increased tissue colonization results in severe Lyme arthritis only in young coinfected mice. At 3 weeks post-infection, diminished pathogen-specific antibody production in coinfected young, but not older mice, as compared to mice infected with each pathogen individually may also contribute to increased inflammation observed due to B. burgdorferi infection, thus causing persistent Lyme disease observed in coinfected mice and reported in patients. Thus, higher combined proinflammatory response to B. burgdorferi due to Th1 and Th17 cells likely reduced B. microti parasitemia significantly only in young mice later in infection, while the presence of B. microti reduced humoral immunity later in infection and enhanced tissue colonization by Lyme spirochetes in these mice even at the acute stage, thereby increasing inflammatory arthritis

Evalaution of radioiodination of synthesised meta-iodobenzylguanidine catalyzed by in situ generated Cu(i)

Meta-iodobenzylguanidine (m-IBG) is a biogenic amine precursor, noradrenaline analogue, which is actively taken up by tumors. In tracer amounts, [123/131I]-m-IBG is used as a radiopharmaceutical to target normal and malignant tissues of neuroadrenergic origin for diagnostic scintigraphy, and labeled with higher activities of 131I, it is used for therapy of phenochromocytoma and neuroblastoma. The increased clinical therapeutic use of unlabeled m-IBG at doses of up to 40 mg/m2 emphasizes the need for syntheses and an established quality protocol for this substance that relies on verifiable analytical parameters. Evaluation of radioiodination was necessary to obtain higher labeling yield (we achieved over 90% instead no more than 70%), because isotopic exchange labeling of m-IBG with 131I catalyzed by Cu(I) is much more efficient than with conveniently used ammonium sulphate.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Protozoan parasite babesia microti subverts adaptive immunity and enhances lyme disease severity

Lyme disease is the most prominent tick-borne disease in the United States. Co-infections with the tick-transmitted pathogens Babesia microti and Borrelia burgdorferi sensu stricto are becoming a serious health problem. B. burgdorferi is an extracellular spirochete that causes Lyme disease while B. microti is a protozoan that infects erythrocytes and causes babesiosis. Testing of donated blood for Babesia species is not currently mandatory due to unavailability of an FDA approved test. Transmission of this protozoan by blood transfusion often results in high morbidity and mortality in recipients. Infection of C3H/HeJ mice with B. burgdorferi and B. microti individually results in inflammatory Lyme disease and display of human babesiosis-like symptoms, respectively. Here we use this mouse model to provide a detailed investigation of the reciprocal influence of the two pathogens on each other during coinfection. We show that B. burgdorferi infection attenuates parasitemia in mice while B. microti subverts the splenic immune response, such that a marked decrease in splenic B and T cells, reduction in antibody levels and diminished functional humoral immunity, as determined by spirochete opsonophagocytosis, are observed in co-infected mice compared to only B. burgdorferi infected mice. Furthermore, immunosuppression by B. microti in coinfected mice showed an association with enhanced Lyme disease manifestations. This study demonstrates the effect of only simultaneous infection by B. burgdorferi and B. microti on each pathogen, immune response and on disease manifestations with respect to infection by the spirochete and the parasite. In our future studies, we will examine the overall effects of sequential infection by these pathogens on host immune responses and disease outcomes. Copyright © 2019 Djokic, Akoolo, Primus, Schlachter, Kelly, Bhanot and Parveen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Electrochemical separation of 90-yttrium in the electrochemical 90Sr/90Y generator and its use for radiolabelling of DOTA-conjugated somatostatin analog [DOTA0, Tyr3] octreotate

Radiopharmaceuticals based on 90Y are widely used in the treatment of malignant deseases. In order to meet the requirements for their future application, a 90Sr/90Y generator was developed and 90Y eluted from this locally produced generator was used for the radiolabelling of the DOTA-conjugated somatostatin analog [DOTA0,Tyr3] octreotate and the preparation of [90Y-DOTA0,Tyr3] octreotate (90Y-DOTATATE) for peptide receptore radionuclide therapy. 90Sr/90Y generator was based on the electrochemical separation of 90Y from 90Sr in a two-cycle electrolysis procedure. Three electrode cells were used to perform both electrolyses. In both cycles, working electrodes were kept on constant potential. The pH of the solution was adjusted to 2.7 of the value before the electrolyses. The radionuclidic purity of the 90Y solution was analysed by ITLC and extraction paper chromatography. The labelling of peptide (100 mg DOTATATE) with 90YCl3 was performed at 95°C for 30 minutes. Radiochemical purity was determined by HPLC and chromatographic separation, using a solid SepPak C-18 column. Results obtained confirmed the efficiency of our electrochemical separation technique and quality control methods for 90Y. The achieved efficiency of the 90Sr/90Y generator above 96% of the theoretical value represents a good basis for the further development of this generator. The labelling of the DOTATATE with 90Y exhibited a high efficiency, too: there was less than 1% of 90Y3+in the 90Y-DOTATATE

Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil

Petrochemical plastics are generally recalcitrant to microbial degradation and accumulate in the environment. Biodegradable polymers obtained synthetically like poly(epsilon-caprolactone) (PCL) or poly-hydroxyalkanoates (PHA), obtained biotechnologically, have shown great potential as a replacement for petroleum-based plastics. Nevertheless, their biodegradation and environmental faith have been less examined. In this study, thin films of PCL (200 mu m) and medium chain length PHA (mcl-PHA, 70 M fraction of 3-hydroxyoctanoate and 30 M fraction of 3-hydroxydecanoate, 600 mu m) were exposed to total protein preparations (extracellular proteins combined with a crude cell extract) of soil isolates Pseudomonas chiororaphis B-561 and Streptomyces sp. BV315 that had been grown on waste cooking oil as a sole carbon source. Biodegradation potential of two polyesters was evaluated in buffer with total protein preparations and in a laboratory compost model system augmented with selected bacteria. Overall, PCL showed better biodegradation properties in comparison to mcl-PHA. Both materials showed surface erosion after 4-weeks of exposure to total protein preparations of both strains, with a moderate weight loss of 1.3% when P. chlororaphis13-561 was utilized. In laboratory compost model system PCL and mcl-PHA showed significant weight loss ranging from 13 to 17% when Streptomyces sp. BV315 culture was used. Similar weight loss of PCL and mcl-PHA was achieved for 4 and 8 weeks, respectively indicating slower degradation of mcl-PHA. Growth on waste cooking oil as a sole carbon source increased the potential of both tested strains to degrade PCL and mcl-PHA, making them good candidates for augmentation of compost cultures in waste management of both waste cooking oils and biodegradable polymers.Related to published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/1246]This is the peer reviewed version of the paper: Mandić, M., Spasić, J., Ponjavić, M., Nikolić, M. S., Cosović, V. R., O’Connor, K., Nikodinović-Runić, J., Đokić, L., & Jeremić, S. (2019). Biodegradation of poly(epsilon-caprolactone) (PCL) and medium chain length polyhydroxyalkanoate (mcl-PHA) using whole cells and cell free protein preparations of Pseudomonas and Streptomyces strains grown on waste cooking oil. Polymer Degradation and Stability, 162, 160–168.[ https://doi.org/10.1016/j.polymdegradstab.2019.02.012

The impact of Mediterranean oscillations on periodicity and trend of temperature in the valley of the Nisava river - a fourier and wavelet approach

Periodicity of temperature on three stations in the Nisava River valley in period 1949-2014, has been analyzed by means of Fourier and wavelet transforms. Combined periodogram based on fast Fourier transform shows considerable similarity among individual series and identffies significant periods on 2.2, 2.7, 3.3, 5, 6-7, and 8.2 years in all datasets. Wavelet coherence analysis connects strongest 6-7 years spectral component to Mediterranean oscillation, starting in 1980s. Combined periodogram of Mediterranean oscillation index reveals 6-7 years spectral component as a dominant mode in period 1949-2014. Wavelet power spectra and partial combined periodograms show absence of 6-7 years component before 1975, after which this component becomes dominant in the spectrum. Consistency between alternation in temperature trend in the Nisava River valley and change in periodicity of Mediterranean oscillation was found

Supplementary data for article: Đokić-Stojanović, D. R.; Todorović, Z. B.; Troter, D. Z.; Stamenković, O. S.; Veselinović, L. M.; Zdujić, M. V.; Manojlović, D. D.; Veljković, V. B. Triethanolamine as an Efficient Cosolvent for Biodiesel Production by Cao-Catalyzed Sunflower Oil Ethanolysis: An Optimization Study. Hemijska Industrija 2019, 73 (6), 351–362. https://doi.org/10.2298/HEMIND190822033D

Supplementary material for: [https://doi.org/10.2298/HEMIND190822033D]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3797