100 research outputs found
Eestis ringlevate HIV-1 CRF06_cpx ja tema rekombinantsete viiruste looduslikud polümorfismid ja ülekanduv ravimresistentsus
Väitekirja elektrooniline versioon ei sisalda publikatsioone.Viimastel kümnenditel on HIV-1 infektsioon muutunud maailma üheks olulisemaks nakkushaiguseks. HIV-1 on väga mitmekesine jagunedes nelja gruppi (M, N, O ja P), millest grupp M on jaotatud 9 subtüübiks ja kümneteks rekombinantseteks vormideks. Põhimõtteline murrang HIV vastases ravis saavutati 1990ndate keskel, mil kasutusele võeti HAART – kombinatsioon kolmest või enamast antiretroviirus (ARV) ravimist, mis on suunatud vähemalt kahe erineva sihtmärgi vastu. Siiani on jäänud ARV ravi üheks olulisemaks probleemiks kiiresti kujunev ravimresistentsus (RR), mille tagajärjel on tõusnud ka ülekanduv RR. Lisaks on teadmata HIV-1 subtüüpide mõju RR tekkele.
Eestis sai kontsentreeritud HIV epideemia alguse 2000. aastal kui hakkas kiirelt levima siiani Euroopas haruldane HIV-1 CRF06_cpx tüvi. Demograafiliselt on Eesti HIV epideemia sarnane Ida-Euroopa omale, kus nakatunuteks olid põhiliselt noored meessoost süstivad narkomaanid.
Käesoleva töö eesmärk oli määrata: (i) Eestis levinud HIV-1 CRF06_cpx viiruse looduslikult levinud RR mutatsioonid peamiste ARV ravimite märklaud piirkondades (proteaas, revertaas ja integraas); (ii) ülekanduva RR määr vahetult peale intensiivse ARV alustamist; (iii) CRF06_cpx viirustüve mõju RR mutatsioonide kujunemisele.
Töö käigus selgus, et:
1. Eesti HIV-1 CRF06_cpx viirustel ei esine loodulikke RR mutatsioone ei PR, RT ega IN piirkondades, mis näitab, et need viirused on tundlikud kõigile laialtlevinud ARV ravimitele. Samas leiti, et Eesti HIV-1 CRF06_cpx viirusel esinevad mitmed looduslikud polümorfismis PR ja IN piirkonnas.
2. Ülekandunud RR oli 2008. aastaks tõusnud 5,5%. Nimetatud tase on piiriks, kust alates rahvusvahelised ravijuhised soovitavad HIV-1 genotüüpilist RR testi.
3. RR mutatsioonid Eesti CRF06_cpx ravikogemusega viirustel sarnanevad subtüüp B viirustega, viidates nimetatud viiruste sarnasele ravivastusele laiemalt kasutaud ARV ravirežiimide korral.During the last decades HIV-1 infection has emerged as one of the most important infection diseases. Based on HIV-1 diversity these viruses can be divided into four groups (M, N, O and P) from which group M contains 9 subtypes and tens of recombinant forms. Breakthrough in HIV treatment took place in mid-1990s when HAART was introduced. It contains the combination of three or more antiretroviral (ARV) agents against at least two different targets. The major problem in HIV treatment is emerging drug resistance (DR) and due to that also the increasing number of transmitted DR. Additionally, the influence of HIV-1 subtypes on DR is unknown.
In Estonia the concentrated HIV epidemic burst in year 2000 when rare recombinant CRF06_cpx was introduced into the population of mainly young male intravenous drug users.
The aim of current study was to determine: (i) natural DR mutations of HIV-1 CRF06_cpx in main ARV agents target regions (protease, revertase and integrase); (ii) the level of transmitted DR; (iii) the influence of CRF06_cpx on the development of DR mutations.
Current study revealed that:
1. Estonian CRF06_cpx viruses do not possess natural DR mutations in PR, RT and IN regions indicating that these viruses are susceptible to all main ARV classes. However, Estonian HIV-1 CRF06_cpx viruses possess several naturally occurring polymorphisms in PR and IN region.
2. In 2008 the level of transmitted DR has been raised to 5.5% which is the threshold for the pretreatment HIV genotypic DR testing by the international HIV treatment guidelines.
3. The pattern of treatment experienced HIV-1 CRF06_cpx viruses are comparable to that seen in subtype B viruses suggesting their similar response to the most widely used ARV therapies
Immunoloogiliste faktorite mõju HIV-i, B-hepatiidi ja C-hepatiidi viirustesse nakatumisele süstivate narkomaanide hulgas
Väitekirja elektrooniline versioon ei sisalda publikatsioone.Inimese immuunpuudulikkuse viirus (HIV), B-hepatiidi viirus (HBV) ja C-hepatiidi viirus (HCV) põhjustavad nii maailmas kui ka Eestis mitmeid terviseprobleeme. Nende viiruste nakatumisteed on sarnased ja seega on sagedane samaaegne haigestumine nii HIV kui ka hepatiidi viirustega. Eriti suur on probleem süstivate narkomaanide (SN) seas. Kuigi süstimise teel levivad HIV, HBV ja HCV väga efektiivselt, on mitmeid inimesi, kes nende viirustega ei nakatu (eksponeeritud seronegatiivsed inimesed – ESN). Siiani ei ole teada nende mitte-nakatumise põhjuseid, kuid vastavate mehhanismide väljaselgitamine võib aidata võidelda viirusnakkuste levikuga või hõlbustada uute ravimite välja töötamist. Varasemad uuringud seksuaalsel teel eksponeeritute seas on näidanud, et HIV-i nakatumist mõjutavad ka inimese geneetilised ja immunoloogilised faktorid, sealhulgas T rakkude hulk ning jaotus.
Käesoleva töö eesmärgiks oli kirjeldada, kuidas T rakkude jaotus ja interleukiin 10 (IL-10) polümorfismid mõjutavad HIV-i nakatumist ja kuidas HIV-i koosesinemine HBV ja HCV-ga ning süstiv narkomaania mõjutavad T rakkude jaotust SN-idel.
Uuringusse kaasati 345 SN-i ja 496 veredoonorit ning T rakkude analüüsiks lisaks 45 vanusele ja soole kohandatud tervet vabatahtlikku. Interleukiin 10 (IL-10) polümorfismid määrati reaalaja PCR-iga ning T rakkude analüüs teostati voolutsütomeetriga.
Uuringus leiti, et IL-10 –1082A ja –592A alleelid kaitsevad HIV nakkuse eest ja –592AC-d sisaldavad genotüübi paarid kaitsevad HIV ning HBV nakkuste eest SN-ide seas. Sarnaselt seksuaalsel teel nakatunud ESN-idele, on narkootikume süstivatel ESN-idel kõrgem immuunaktivatsioon, kõrgem CD45RA+RO+ rakkude protsent ja madalam CCR5 ekspresioon kui tevetel vabatahtlikel. HBV+HCV+ kaksiknakkusega SN-idel on muutunud ainult CD4+ rakkude arvukus, mis näitab, et HBV ja/või HCV seropositiivsus omab vähest mõju T raku jaotusele. HIV–HBV–HCV– SN-idel on muutunud mälurakude jaotus, kõrgem immuunaktivatsioon ja rohkem CCR5+ rakke võrreldes tervete vabatahtlikega. Seega mõjutab ka süstiv narkomaania HIV-st, HBV-st ja HCV-st sõltumata T rakkude jaotust.Intravenous drug use is one of the most important transmission routes for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Despite repeated exposure some individuals remain uninfected (exposed seronegative individuals –ESN). The reasons for remaining seronegative are not yet fully understood. The protection against HIV, HBV, and HCV has been associated with multiple genetic polymorphisms and immunological factors such as T cell distribution. However, majority of studies have been conducted in sexually exposed subjects and data regarding persons who inject drugs (PWID) is limited. We aimed to describe whether IL-10 polymorphisms influence HIV, HBV, and HCV susceptibility and how exposure and seropositivity to these viruses influence T cell distribution among Caucasian PWID.
A total of 345 PWID, 496 blood donors, and 47 healthy volunteers were recruited. The IL-10 –592C/A and –1082A/G polymorphisms were determined using Real-Time PCR and T cell distribution using multicolor flow cytometry.
We found, that the presence of low IL-10 producing alleles –1082A and –592A protects highly exposed PWID against HIV and HBV infections. In terms of T cell distribution, similarly to sexually exposed ESN, individuals with parenteral exposure have increased immune activation, increased percentages of CD45RA+RO+ cells and lower CCR5 expression on CD4+ cells compared to healthy volunteers. The T cell distribution among triple infected individuals HIV+HBV+HCV+ was similar to the one seen in previous studies among HIV mono-infected individuals (lower percentages of CD4+ and increased immune activation) and therefore probably triggered by the HIV infection. HBV and/or HCV co-infections had a minimal effect to these changes. Additionally to HIV, HBV/HCV double-infection influenced only the percentages of CD4+ T cells and the seropositivity to these viruses has a minimal effect to T cell distribution. Whereas intravenous drug use appeared to influence T cell distribution towards immune activation and increase in HIV co-receptor CCR5 expression
HIV-1 ülekanduva ravimresistentsuse esinemine 2010.aastal HIV-diagnoosi saanud isikutel Eestis
http://tartu.ester.ee/record=b2655889~S1*es
Implementation of Balanced Scorecard
Diploma thesis is dealing with analysis of strategy based on interview with management of firm Chromservis s.r.o. Then author uses methods and techniques of strategy analysis to analyse finacial situation, firm's cumtomers, competitors, suppliers and potential substitutes. Final point of analytical part is comparison of the results with firms in the same branch and SWOT analysis. Finally author suggests system of strategic objectives, measurements and connections among objectives. As the last point the objectives are drawn in the strategy map of Balanced Scorecard
Versification analysis in B. Yakubskyy’s interpretation
Ідеться про книгу Б. Якубського «Наука віршування», його дослідження і
методи аналізу вірша.B. V. Yakubsky is a Ukrainian specialist in literature. Investigating the Ukrainian
classical literature (works of T. Shevchenko, Lesya Ukrainka, O. Kobylianska and
others), the author concentrated mostly on the problems of theory and methodology
of literature, in particular on learning Ukrainian versification. His observations and
conclusions were stated in the work «The science of versification» in a proper form.
It is the first attempt to introduce the academic knowledge of the theory of Ukrainian
poetry based on the materials of ancient and modern Ukrainian poetry
The Infrastructure Investment in the Krkonoše National Park Area
Tato diplomová práce se věnuje investicím do infrastruktury na území Krkonošského národního parku. První kapitola práce zmiňuje teoretická východiska, která jsou nezbytná pro následující analýzu současného stavu infrastruktury, návrh na změnu a zhodnocení navrhovaného řešení. Druhá část práce je věnována analýze a investičním i neinvestičním nákladům spojených s údržbou, opravami a rekonstrukcemi cest na území Krkonošského národního parku. Třetí část se potom věnuje návrhu na změnu současného stavu pomocí zavedení nových technologií a poslední kapitola zhodnocuje navrhované změny.This thesis deals with the infrastructure investment in the Krkonoše national park area. In the first part the author mentions theoretical starting-points which are necessary for the following analysis of the current infrastructure, also suggests changing the present condition and evaluates the suggested solution. In the second part the author analyses the current condition of the infrastructure and both investment and non-investment costs which are required for road maintenance, repairs and reconstruction in Krkonoše national park. In the third part deals with describing how to implement new technologies to change the current condition. In the last part the author evaluates her suggested changes.Dopravní fakulta Jana PerneraDiplomantka přednesla ucelenou a logicky uspořádanou obhajobu své diplomové práce. V ní dokázala přesvědčivým způsobem obhájit závěry svých řešení. Na poznámky, resp. připomínky oponenta reagovala správně a v plném rozsahu je zodpověděla. U doplňkových otázek prokázala schopnost logického myšlení, pohotové reakce, jasného a srozumitelného vysvětlení.Dokončená práce s úspěšnou obhajobo
The Byzantine “Chants” of the Contemporary Bulgarian Theatre Texts, Contexts, Figures
The article is dedicated to the problems of historical drama, one of the ways of interpreting the past. The study is placed in the context of the sociology of culture and the historical memory of society, with a focus on the transposition and the symbolical representation of the history of Byzantium and the Second Bulgarian Kingdom (1181–1396) in literature. The subject of the analysis are the works of the Bulgarian poet and playwright Radko Radkov (1940–2009), above all his play Theophano, written in the convention of classical drama in verse and the so-called ritual drama, according to the title of the author, a synthesis of text borrowed from Old Bulgarian Literature, and Byzantine hymnography, inspired visually by the images of the Middle Age Miniatures included in Manassij’s Chronicle (Codex Vaticanus Slav II) – Praise of Turnovgrad and In Praise of the Word. The historical theme in the work of Radko Radkov is substantially different from the interpretation of the Bulgarian history of other Bulgarian writers of the second half of the 20th Century, by which the author is opposing the ideological constructs of the official authorities during this period. Within the discourse of the relations between creator and authorities, attention is paid to some events surrounding the 1300 anniversary of the creation of the Bulgarian state (celebrated in 1981), when, thanks to the benevolence of Lyudmila Zhivkova and the open culture policy that she, as Chairperson of the Committee of Arts and Culture, had introduced, the plays of Radko Radkov were allowed to be staged in the theatres. The playwright has found semiotic and stylistic devices that recreate the classical past of the people, the orthodox Christianity and culture in the universal perspective of the Byzantine Commonwealth, and artistically voice his historiosophic views concerning Bulgarian national history and the Byzantine-Bulgarian cultural community. The paper analyses the tribulations of the performance of Theophano, staged in Bulgaria by the French Director Pierre Della Torre, who sees in the poetic world of Radko Radkov “the monumental force of the masters of French theatre, Racine and Corneille”
The Fate of General Radko Dimitriev and His Memory in Context of Russian-Bulgarian Relations of the Late 19th – Early 20th centuries
This article examines the biography of the Bulgarian-born General Radko Dimitriev (1859–1918), who was convinced that the good of his homeland was inextricably linked with Russia and depended on good relations with it. For this good, he went to the overthrow of the monarch, but a decade later due to changes in the vector of Bulgarian policy was able to return home and become a hero. In 1913–1914, R. Dimitriev served as Bulgaria's envoy to Russia and tried to change the negative image of his country. With the outbreak of World War I, he joined the Russian army, and a year later in Bulgaria he was declared a deserter and a traitor. In 1918 he was executed by the Bolsheviks in Pyatigorsk, and in a few decades he became practically a symbol of friendship between the Bulgarian and Russian peoples, which led to retouching the circumstances of his death. The article traces the actions of the General and his motivation. Despite his Bulgarian origin, in 1914 he became nearly the main hero of the war in the Russian public space. The reasons for its popularity were not only in the im-portance of his victories, but also in the fact that R. Dimitriev was called the incarnation of A. V. Suvorov and M. D. Skobelev. The article shows what values, embodiments of which were these popular warlords, were characteristic this Bulgarian general. This is a personal part in the fighting, the care of soldiers, democracy in communication. Modern Russian military also has moved to a new paradigm of command, which, however, worked against their popularity among the soldiers. And at the same time, values of the commander of Suvorov's or Skobelev's types were insolvent in the conditions of revolutionary commotion, and R. Dimitriev lost control of the parts entrusted to it. Because of their gener-osity and love for Russia, he refused to take part in the Civil war that decided his death.The author declares absence of conflict of interest
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