Submitted by João Arthur Martins (joao.arthur@ufpe.br) on 2015-03-10T19:07:24Z No. of bitstreams: 2 Dissertaçao Hesdras Viana.pdf: 2998238 bytes, checksum: de42b675472ac4632a3a3c04688a77d5 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Approved for entry into archive by Daniella Sodre (daniella.sodre@ufpe.br) on 2015-03-10T19:43:06Z (GMT) No. of bitstreams: 2 Dissertaçao Hesdras Viana.pdf: 2998238 bytes, checksum: de42b675472ac4632a3a3c04688a77d5 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-10T19:43:06Z (GMT). No. of bitstreams: 2 Dissertaçao Hesdras Viana.pdf: 2998238 bytes, checksum: de42b675472ac4632a3a3c04688a77d5 (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2013-02-26 / Extrair características da fala é uma etapa fundamental para os sistemas de reconhecimento de voz. É através dos descritores que extraímos a energia do sinal, a frequência fundamental (pitch) e a estrutura dos formantes que serão utilizados como identificadores para cada palavra pronunciada. Descritores como MFCC (Mel-Frequency Cepstral Coefficient), RASTA-PLP (RelAtive SpecTrAl - Perceptual Linear Predictive) e PNCC (Power Normalized Cepstral Coefficient) são muitos utilizados no estado da arte na área de reconhecimento de voz, porém, essas técnicas não conseguem apresentar bons resultados quando expostos a amostras com presença de ruído, variabilidade de locutor e fala contínua. O objetivo deste trabalho é desenvolver um descritor para a fala que seja invariante ao ruído, ambiente e locução. Para isso, fizemos um estudo dos descritores de voz mais utilizados na literatura, identificando as vantagens e desvantagens, expondo a situações variadas. Para avaliação das técnicas, utilizamos a base NOIZEUS (Noisy Speech Corpus) e dois classificadores: HMM (Hidden Markov Models) e SVM (Support Vector Machine). Essa base tem como característica a presença de ruído variando de 0dB, 5dB, 10dB e 15dB, gravada em diversos ambientes. A utilização dos classificadores serviu para validar os descritores de voz. O descritor proposto, chamado de MINERS (Model Invariant to Noise and Environment and Robust for Speech), apresentou melhores resultados entre todos os descritores avaliados (MFCC, MFCC combinado com Wavelet Denoising, RASTAPLP e PNCC). A abordagem que obteve maior sucesso foi a utilização do MINERS com o classificador SVM.

Since the early 1970’s, Rastafari has enjoyed public notoriety disproportionate to the movement’s size and humble origins in the slums of Kingston, Jamaica roughly forty years earlier. Yet, though numerous academics study Rastafari, a certain lacuna exists in contemporary scholarship in regards to the movement’s scriptural basis. By interrogating Rastafari’s recovery of the Hebrew Bible from colonial powers and Rastas’ adoption of an Israelite identity, this dissertation illuminates the biblical foundation of Rastafari ethics and symbolic registry. An analysis of the body of scholarship on Rastafari, as well as of the reggae canon, reveals the centrality of an Israelite identity for Rastas and its enabling of Rastafari resistance to racial oppression. Furthermore, the Hebrew Bible is, for Rastas, key to an intimate relationship with Jah, for it reveals their chosenness and their inherent divine nature. They both textually confirm this election and enact it through ritual practice. By interrogating the methods Rastas apply to the pages of the Bible in order to ascertain their appointment and decipher proper ritual practice, this dissertation expands scholarly conversations about Rastafari biblical hermeneutics. Centering on readings of Samson and Moses, it suggests that these two biblical actors function as moral exemplars and models of livity for Rastas. Despite the transgressive nature of Samson and Moses, Rastas adopt them as co-practitioners and paradigms of Rastafari election because when Samson and Moses are Rastas, all Rastas can claim their chosenness, strength, and relationship with Jah. / Religion

<p>Hormon rasta ima ključnu ulogu u mnogim fiziolo&scaron;kim procesima, anabolički efekti, stimulisanje rasta dugih kostiju, regulacija transkripcije gena u ciljnim ćelijama su uglavnom posredovani preko mitogenog polipeptida, insulinu sličan faktor rasta tip 1 (insulin like growth factor 1-IGF-1). Hormon rasta indukuje proizvodnju IGF-1 u jetri, koji reaguje sa receptorima ciljnih organa indukujući rast, odnosno IGF-1 posreduje svim stimulativnim dejstvima hormona rasta na kost, hrskavicu, rast mi&scaron;ić a i na metabolizam masti i ugljenih hidrata. U proceni redovnosti, bezbednosti i efikasnosti terapije hormonom rasta koristi se merenje koncentracije IGF-1 u serumu. Istraživanje je urađeno kao retrospektivno-prospektivna studija, a obuhvatilo je 80 pacijenata na terapiji hormonom rasta koja se kontroli&scaron;u i leče na Odeljenju za endokrinologiju, dijabetes i bolesti metabolizma Instituta za zdravstvenu za&scaron;titu dece i omladine Vojvodine u Novom Sadu. Istraživani uzorak je obuhvatio 80 pacijenata, od kojih 35 dece sa nedostatkom hormona rasta, 24 dece rođene male za gestacionu dob i 21 devojčicu sa Tarnerovim sindromom. Svi ispitanici su praćeni od početka primene hormona rasta i tokom prve dve godine terapije hormonom rasta. U ovom istraživanju su praćeni auksolo&scaron;ki i laboratorijski parametri u cilju ispitivanja odgovora na terapiju hormonom rasta. Praćene su bazalne vrednosti IGF-1 i promene nivoa IGF-1 u serumu tokom terapije hormonom rasta i kori&scaron;ćene da bi se ispitao odgovor na terapiju hormonom rasta, praćenjem brzine rasta, promena skora standardnih devijacija - SSD za telesnu visinu i ko&scaron;tanog sazrevanja. Ciljevi istraživanja su bili da se utvrdi povezanost vrednosti insulinu sličnog faktora rasta tip 1, brzine rasta i ko&scaron;tanog sazrevanja tokom terapije hormonom rasta. Takođe je poređena brzina rasta dece sa deficitom hormona rasta, devojčica sa T arnerovim sindromom i dece rođene male za gestaciono doba na terapiji hormonom rasta. U istraživanom uzorku, dvogodi&scaron;njim praćenjem terapije hormonom rasta je postignut dobar odgovor na terapiju, među decom sa nedostatkom hormona rasta je 71,5% postiglo normalnu telesnu visinu (&plusmn;2 SSDTV) posle dve godine terapije hormonom rasta, 79,2% dece rođene male za gestacionu dob i 42,9% devojčica sa Tarnerovim sindromom. Značajna zastupljenost dece prepubertetskog uzrasta na početku terapije hormonom rasta, među decom sa nedostatkom hormona rasta 77,2%, među decom rođenom malom za gestacionu dob 79,1% i među devojčicama sa Tarnerovim sindromom 90,5% &scaron;to je značajno uticalo na uspe&scaron;nost terapije. Tokom terapije hormonom rasta je utvrđeno povećanje brzine rasta i SSD TV kod sve tri grupe ispitanika. U sve tri grupe ispitanika je tokom terapije hormonom rasta utvrđen porast nivoa IGF-1 seruma i SSDIGF-1 i ubrzanje ko&scaron;tanog sazrevanja tokom terapije hormonom rasta. Za prvih &scaron;est meseci terapije nema statistički značajnih razlika među grupama u brzini rasta (p&gt;0,05), dok je za period prve i druge godine terapije hormonom rasta utvrđeno da postoji statistički značajna razlika među grupama (p&lt;0,05), da je brzina rasta kod devojčica za Tarnerovim sindromom statistički značajno manja i od brzine rasta kod dece sa nedostatkom hormona rasta (p &lt;0,05), i od brzine rasta kod dece rođene male za gestacionu dob (p&lt;0,05). Među decom sa nedostatkom hormona rasta i dece rođene male za gestacionu dob nema statistički značajne razlike u brzini rasta (p&gt;0,5). U ovom istraživanju je praćenjem auskolo&scaron;kih i laboratrijskih parametara tokom dvogodi&scaron;nje primene hormona rasta, konstruisano vi&scaron;e matematičkih modela za predviđanje odgovora na terapiju hormona rasta koji su statistički veoma značajani sa visokim koeficijentom vi&scaron;estruke linearne korelacije. U ovom istraživanju nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i brzine rasta za ceo uzorak, kao ni za decu sa nedostatkom hormona rasta, decu rođenu malu za gestacionu dob i devojčice za Tarnerovim sindromom. Nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i ubrzanja ko&scaron;tanog sazrevanja za ceo uzorak i za tri grupe pacijenata.</p> / <p>Growth hormone plays a key role in many physiological processes. The anabolic effects, the stimulation of growth of the long bones and the regulation of gene transcription in the target cells are mediated mainly via mitogenic polypeptide and insulin-like growth factor type 1 (insulin like growth factor 1-IGF-1). Growth hormone induces the production of IGF-1 in the liver, which interacts with receptors of the target organs inducing growth, that is, IGF-1 mediates all the stimulating effects of growth hormone on bone, cartilage, muscle growth and the metabolism of fats and carbohydrates. In assessing the regularity, safety and efficacy of growth hormone therapy, measuring the concentration of IGF-1 in serum is used. The survey was conducted as a retrospective-prospective study and involved 80 patients treated with growth hormone, monitored and treated at the Department of Endocrinology, Diabetes and Metabolic Diseases, at the Institute for Health Protection of Children and Youth of Vojvodina in Novi Sad. Investigated sample included 80 patients, of whom 35 children have growth hormone deficiency, 24 children were born small for gestational age and 21 girls with Turner syndrome. All the patients were monitored from the beginning of the administration of growth hormone and during the first two years of growth hormone therapy. In this study, auxological and laboratory parameters were monitored for the purpose of examining the response to treatment of growth hormone. The basal values of IGF-1 and changes in IGF-1 levels in serum, along with monitoring the rate of growth velocity and recent changes in standard deviation - SSD for body height and bone maturation, were monitored during growth hormone therapy and used for the evaluation of the response to growth hormone therapy. The objectives of the study were to determine the correlation of insulin-like growth factor type 1 values, the growth velocity and maturation of bone during growth hormone therapy. Also, the growth velocity in children with growth hormone deficiency was compared with the growth velocity in girls with Turner syndrome and in children born small for gestational age while treated with growth hormone. Two-year monitoring of growth hormone therapy in the study sample has show n good response to therapy. 71.5% of children with growth hormone deficiency, 79.2% of children born small for gestational age, and 42.9% of girls with Turner syndrome achieved normal body height (&plusmn; 2 SSDTV) after two years of growth hormone therapy. There was a significant share of children at prepubertal age at the beginning of growth hormone therapy: 77.2% of children with growth hormone deficiency, 79.1% of children born small for gestational age and 90.5% of girls with Turner syndrome, which significantly influenced the success of the therapy. During the growth hormone therapy there was an increase of growth velocity and SSD TV in all three groups of children. An increase in levels of IGF-1 serum and SSDIGF-1 and acceleration of bone maturation were determined in all three groups of patients during growth hormone therapy. For the first six months of therapy there was no statistically significant difference between groups in growth velocity (p&gt; 0.05), while the period of the first and second year of growth hormone therapy showed a statistically significant difference between groups (p &lt;0.05). The growth velocity in girls with Turner syndrome was significantly lower than the growth velocity in children with growth hormone deficiency (p &lt;0.05) and in children born small for gestational age (p &lt;0.05). Between children with growth hormone deficiency and children born small for gestational age there was no statistically significant difference in growth velocity (p&gt; 0.5). By monitoring auxological and laboratory parameters during the two years of application of growth hormone, several highly statistically significant mathematical models for predicting the response to treatment of growth hormone were constructed in this study with a high coefficient of multiple linear correlation. In this study, there was no statistically significant correlation between the level of change in IGF-1 and growth velocity for the entire sample, as well as for children with growth hormone deficiency, children born small for gestational age and girls for Turner syndrome. There was no statistically significant correlation between the level of change in IGF-1 and acceleration of bone maturation for the entire sample and for the three groups of patients.</p>

<p>Doktorska disertacija odnosi se na analizu najznačajnijih kriterijuma<br />koje posmatraju investitori prilikom ulaganja na tržišta u razvoju.<br />Poređenjem šest evropskih berzanskih indeksa tržišta u razvoju i<br />svetski najznačajnijeg berzanskog indeksa - S&amp;P 500, dobijeni su<br />rezultati koji ukazuju da postoji značajnost u zavisnosti nivoa cena od<br />kretanja na globalnom tržištu, a koja su posledica postojanja<br />internacionalnih investitora. Dobijeni rezultati mogu se koristiti<br />kao osnova za dalja istraživanja u oblasti od strane akademske<br />zajednice, kao i od strane profesionalnih učesnika na finansijskim<br />tržištima, kao pomoć prilikom donošenja njihovih investicionih<br />odluka. Od posebnog interesa je mogućnost primene rezultata u vođenju<br />ekonomske i finansijske politike Republike Srbije.</p> / <p> markets investors. Comparison of six European emerging stock market<br /> indices and world&rsquo;s the most important stock exchange index - the S&amp;P 500,<br /> established a level of emerging markets price dependence on international<br /> investors with global market overview. The results obtained can be used as a<br /> basis for further research in the field by the academic community, as well as<br /> by professional investors in financial markets, to assist in making their<br /> investment decisions. Of particular interest is the possibility of applying the<br /> results in economic and financial decision making policy of the Republic of<br /> Serbia.</p>

<p>Intrauterusna restrikcija rasta (IUGR) se odnosi na stanje u kojem fetus nije u mogućnosti da ostvari svoj genetski potencijal za rast. IUGR je ozbiljan klinički problem i nedavno je povezan sa bolestima odraslog doba kao &scaron;to su hipertenzija, insulin nezavistan diabetes melitus, dislipidemije i ishemijske bolesti srca. Eritropoetin je glavni regulator proliferacije i diferencijacije eritroidnih progenitorskih ćelija zahvaljujući svojoj antiapoptotičkoj aktivnosti. Cilj istraživanja je bio da se ispita uticaj IUGR na bubrege, kao i uticaj eritropotina na bubrege sa IUGR. Eksperimentalna studija je sprovedena u gajili&scaron;tu Pasterovog zavoda u Novom Sadu na 60 mi&scaron;eva rase NMRI. IUGR je izazivana aplikacijom deksametazona gravidnim ženkama. Po rođenju su mladunci bili podeljeni u sedam grupa. Mladuncima je u 1. i 7. danu života davan darbepoetin alfa (DA) u dozama od 1, 4 i 10&mu;g/kg. Dve grupe su predstavljale potomke majki koje su tokom trudnoće dobile DA. Nakon 4 nedelje su uzimani uzorci bubrega i vr&scaron;ena je morfolo&scaron;ka i stereolo&scaron;ka analiza glomerula. Aplikacija deksametazona (100 &mu;g/kg) trudnim mi&scaron;icama dovodi do potomstva sa IUGR. Primena DA kod novorođenih mi&scaron;eva sa IUGR dovodi do bržeg porasta telesne mase u prvih 7 dana života (&bdquo;catch-up― rasta). Mi&scaron;evi rođeni sa IUGR imaju manju povr&scaron;inu glomerula bubrega. Primena DA nakon rođenja i u 7. danu života (4 i 10 &mu;g/kg) kod novorođenih mi&scaron;eva sa IUGR dovodi do hipertrofije glomerula bubrega. IUGR nema uticaja na broj glomerula bubrega mi&scaron;eva. Primena DA nema uticaja na broj glomerula bubrega mi&scaron;eva. Mi&scaron;evi rođeni sa IUGR imaju manju debljinu korteksa bubrega. Primena DA (4 i 10 &mu;g/kg) kod mi&scaron;eva rođenih sa IUGR dovodi do povećanja debljine korteksa bubrega. Davanje DA kod IUGR značajno povećava povr&scaron;inu glomerula i debljinu korteksa bubrega.</p> / <p>Intrauterine growth restriction (IUGR) refers to a condition in which a foetus is not able to achieve its genetic potential for growth. IUGR is a serious clinical problem, and has recently been linked with diseases of adulthood, such as hypertension, insulin-independent diabetes mellitus, dyslipidemia, and ischemic heart disease. Erythropoietin is the major regulator of proliferation and differentiation of erythroid progenitor cells, thanks to its anti-apoptotic activities. The aim of this study was to investigate the effect of IUGR on the kidneys, and the impact of erythropoietin on the kidneys with IUGR. The experimental study was conducted in Pasteur Institute of Novi Sad on 60 mice of NMRI race. IUGR has been imposed with the application of dexamethasone to pregnant females. After birth, the pups were divided into seven groups. DA was administered to the pups on the 1st and 7th day of life (dose 1, 4 and 10 &mu;g/kg). Two groups represented the offspring of the mothers who during pregnancy received DA. After 4 weeks, kidney samples were taken and morphological and stereological analysis of the glomeruli was performed. The application of dexamethasone (100 &mu;g/kg) to pregnant mice leads to their offspring with IUGR. Application of DA to newborn mice with IUGR leads to faster weight gain in the first 7 days of life (&quot;catch-up&quot; growth). Mice born with IUGR have a reduced glomerular surface. Application of DA after birth and on the 7th day of life (4 and 10 &mu;g/kg) in mice with IUGR leads to hypertrophy of the kidney glomeruli. IUGR has no effect on the number of kidney glomeruli. Application of DA has no effect on the number of kidney glomeruli. Mice born with IUGR have a reduced cortical thickness. Application of DA (4 and 10 &mu;g/kg) in mice born with IUGR leads to increased thickness of the kidney cortex. Application of DA to mice with IUGR significantly increases the surface area of the kidney glomeruli and cortical thickness.</p>

Cette thèse s’intéresse à la variabilité de la relation mass-diamètre (m(D)) des hydrométéores en phase glace présents dans les systèmes convectif de moyenne échelle (MCS). Elle s’appuie sur une base de données acquise pour 4 types de MCS différents durant 4 campagnes de mesure aéroportée : (i) MCS de la mousson Africaine (Continent ; MT2010), (ii) MCS de l’océan Indien (MT2011), (iii) MCS de la Méditerranée (côtes ; HyMeX), (iv) MCS de la mousson Nord-Australienne (côtes ; HAIC-HIWC). La relation m(D) est calculée à partir de l’analyse combinée des images des hydrométéores enregistrées par les sondes optiques et les facteurs de réflectivité mesurés à l’aide d’un radar Doppler embarqués sur le même avion de recherche. Il est d’usage que la relation m(D) des hydrométéores soit représentée par une loi puissance (avec un pré-facteur et un exposant), qui doit être contrainte par des informations supplémentaires sur les hydrométéores. Une étude théorique sur les formes des hydrométéores à l’aide de simulations en 3 dimensions dans lesquelles les hydrométéores sont orientés aléatoirement et projeté sur un plan, permet de contraindre l’exposant β de la relation m(D) en fonction de l’exposant σ de la relation surface-diamètre (S(D)). La relation S(D) est aussi représentée par une loi puissance, et elle peut-être calculée pour une population d’images d’hydrométéores enregistrés par les sondes optiques. La variabilité de l’exposant est finalement calculée à partir de la variabilité de l’exposant σ déduis des images des hydrométéores. Ensuite le pré-facteur α est calculé à partir de simulations des facteurs de réflectivité, de sorte que les facteurs de réflectivité simulés soient égaux aux facteurs de réflectivité mesurés par le radar nuage le long de la trajectoire de l’avion dans les MCS. Des profils moyens en fonction de la température sont calculés pour les coefficients de la relation m(D), les distributions en tailles des hydrométéores et les contenus massiques de glace dans les MCS (CWC). Les profils moyens pour les quatre types de MCS sont différents les uns des autres. Pour les quatre types de MCS, il est montré que les variations des coefficients de la relation m(D) sont corrélées avec les variations de la température. Four types de paramétrisations de la relation m(D) sont calculées depuis l’analyses des variations des coefficients de la relation m(D). Le bénéfice apporté par l’utilisation de relation m(D) non constante contrairement à l’utilisation de relation m(D) avec α et β constant, est démontré en étudiant l’impact de toutes les paramétrisations de la relation m(D) sur le calcul des relations Z-CWC et Z-CWC-T. / This study focuses on the variability of mass-diameter relationships (m(D)) and shape of ice hydrometeors in Mesoscale Convective Systems (MCS). It bases on data base which were recorded during four airborne measurement campaigns: (i) African monsoon’s MCS (continent; MT2010), (ii) Indian Ocean’s MCS (MT2011), (iii) Mediterranean’s MCS (costs; HyMeX), (iv) North-Australian monsoon’s MCS (costs; HAIC-HIWC). m(D) of ice hydrometeors are derived from a combined analysis of particle images from 2D-array probes and associated reflectivity factors measured with a Doppler cloud radar on the same research aircraft. Usually, m(D) is formulated as a power law (with one pre-factor and one exponent) that need to be constrained from complementary information on hydrometeors. A theoretical study of numerous hydrometeor shapes simulated in 3D and arbitrarily projected on a 2D plan allowed to constrain the exponent β of the m(D) relationship from the exponent σ of the surface-diameter S(D) relationship, which is likewise written as a power law. Since S(D) always can be determined for real data from 2D optical array probes or other particle imagers, the evolution of the m(D) exponent can be calculated. After that, the pre-factor α of m(D) is constrained from theoretical simulations of the radar reflectivity factor matching the measured reflectivity factor along the aircraft trajectory. Mean profiles of m(D) coefficients, particles size distributions and Condensed Water Content (CWC) are calculated in functions of the temperature, and are different for each type of MCS. For the four types of MCS, it is shown that the variability of m(D) coefficients is correlated with the variability of the temperature. Four types of m(D) parametrisations are calculated since the analysis of the variability of the m(D) coefficients. The significant benefit of using variable m(D) relations instead of a single m(D) relationship is demonstrated from the impact of all these m(D) relations on Z-CWC and Z-CWC-T fitted parametrisations.

<p>Dijabetesna retinopatija je među vodećim uzročnicima stečenog slepila, kako u razvijenim zemljama, tako i zemljama u razvoju. Dijabetesna retinopatija je jedna od<br />najče&scaron;ćih komplikacija Dijabetes Mellitus-a. U sklopu dijabetesne retinopatije jedan od najranijih razloga koji dovodi do pada vidne o&scaron;trine je dijabetični makularni edem (DME). Pad vidne o&scaron;trine kod pacijenata sa dijabetesom naru&scaron;ava njihov kvalitet života i umanjuje radnu sposobnost. Dosada&scaron;nji oblik lečenja laserfotokoaguacijom makule, nije dao zadovoljavajuće rezultate. U novije vreme sve vi&scaron;e je zastupljeno farmakolo&scaron;ko lečenje edema koje podrazumeva intrvitrealnu aplikaciju lekova iz grupe inhibitora vaskularnog endotelnog faktora rasta (VEGF inhibitori), koji dovodi do stabilizacije zidova krvnih sudova.&nbsp;<br />Cilj ove studije je da se ispita efikasnost lečenja DME uz pomoć intravitrealno aplikovanih lekova iz grupe inhibitora vaskularnog endotelnog faktora rasta u odnosu na konvencionalno do sada priznato lečenje laserfotokogulacijom makule.&nbsp;<br />Efikasnost lečenja je procenjivana na dva načina: anatomski, na osnovu smanjenja centralne makularne debljine izražene u &mu;m, merene metodom optičke koherentne tomografije, i funkcionalno, na osnovu pobolj&scaron;anja vidne o&scaron;trine koja je izražavana u log MAR jedinicama. U ovoj prospektivnoj, randomiziranoj kliničkoj studiji sa minimumom praćenja od 6 meseci, u eksperimentalnoj grupi tretiran je 51 pacijent,<br />odnosno 84 oka aplikacijom bevacizumaba (anti VEGF agens) u dozi od 1,25 mg, sa ili bez dodatnog laser tretmana.&nbsp;<br />Uz prosečno 2,46 inekcije postignuta je prosečna redukcija centralne makularne debljine od 139,15 &mu;m.&nbsp; Dobijene vrednosti su nakon svake aplikovane doze su značajno bolje u odnosu na početnu. Edemi sa većom centralnom makularnom debljinom su zahtevali tretman sa većim brojem inekcija. Kod većih edema je postignuta i veća redukcija centralne makularne debljine. U odnosu na vidnu o&scaron;trinu u eksperimentalnoj grupi postignuto je pobolj&scaron;anje od 0,135 log MAR jedinica. Efekat lasera kao samostalne terapije u kontrolnoj grupi (50 pacijenata, 92 oka) nije bio<br />značajan ni u pogledu smanjenja centralne makularne debljine kao ni na osnovu pobolj&scaron;nja vidne o&scaron;trine. Tretman bevacizumabom samostalno ili u kombinaciji sa laserom je efikasniji u tretmanu DME u odnosu na konvencionalni tretman laserfotokoaguacijom koji potvrđeno dovodi do stabilizacije stanja. Značaj ove studije je potvrda efikasnosti i bezbednosti jednog novog oblika lečenja koji samostalno ili u kombinaciji sa laser tretmanom predstavlja novi protokol lečenja dijabetičnog makularnog edema.</p> / <p>Diabetic retinopathy is among the leading causes of acquired blindness in developed countries, as well as in developing countries. Diabetic retinopathy is one of the most frequent Diabetes Mellitus complications. Within diabetic retinopathy, diabetic macular edema (DME) is one of the earliest causes of the loss of visual acuity. Impaired vision causes decline in life quality in diabetic patients and it decreases their<br />working ability. Up to this date, laser photocoagulation treatment has not given<br />satisfactory results. Recently, new promising treatment forms have emerged, including the intravitreal application of vascular endothelium growth factor (VEGF inhibitors), which lead to stabilization of the vessel wall. The aim of this study is to evaluate the efficacy of DME treatment consisting of intravitreal&nbsp; VEGF inhibitor application alone or as a part of combined treatment (intravitreal VEGF inhibitor plus laser photocoagulation) compared with conventional laser treatment alone. The effect of treatment was evaluated according to morphological parameters by measuring central macular thickness (CMT) in &mu;m with optical coherence tomography, and according to functional parameter by visual acuity in log MAR scale. In this prospective randomized clinical trial, with minimum follow up of 6 months, in experimental group 51 patient, or 84 eyes were treated with bevacizumab (VEGF inhibitor) in 1.25 mg dosage, alone or in combination with laser. The mean reduction in was 139.15 &mu;m, which was achieved with 2.46 doses on average. The difference between the final and initial CMT values after each dos age was tatistically significant.<br />Edemas with high central macular thickness required high number of intraviteal<br />aplicatons and the reduction was higher. In our study, mean visual acuity improved significantly in 0.135 log MAR. In control group (50 patient, 92 eyes) treated with laserphotocolagulation alone, the effect on visual acuity and central acular thickness was not statistically significant. The treatment with bevacizumab alone or in combined<br />treatment is more effective in treating DME than conventional macular laser treatment alone, from both - anatomical and functional perspective. The importance of this study is confirmation of the efficacy and safety of a new form of treatment and the introduction of a new protocol for the treatment of diabetic macular edema.</p>

<p>Receptor epidermalnog faktora rasta (EGFR) pripada porodici receptora protein-tirozin kinaze čija je aktivacija povezana sa proliferacijom malignih, invazijom, inhibicijom apoptoze, tumorskom angiogenezom i metastatskim &scaron;irenjem stoga ima važnu ulogu u karcinogenezi i tumorskoj progresiji. Aktivirane mutacije se odvijaju oko katalitičkog tirozin kinaza domena. Biopsijski, citolo&scaron;ki i hirur&scaron;ki uzorci se koriste u detekciji EGFR mutacija u momentu postavljanja dijagnoze adenokarcinoma ili karcinoma sa komponentom adenokarcinoma, najpouzdanije lančanom reakcijom polimeraze. Činjenica da primena ciljane molekularne terapije tirozin kinaza inhibitorima kod obolelih sa EGFR mutiranim adenokarcinomom pluća pobolj&scaron;ava prognozu bolesti, postoji rezistencija kod pojedinih tipova EGFR mutacija i povezanost histopatolo&scaron;kim i imunohistohemijskim karakteristikama tumora, da je bronholo&scaron;ki uzorak često jedini uzorak u kome je potrebno odrediti i molekularni profil tumora osnovni cilj ove disertacije bio je da se odredi učestalost i tip EGFR mutacija i povezanost sa karakteristikama adenokarcinoma. Da bi se taj cilj realizovao postavljeni su sekundarni ciljevi odnosno da se: izvr&scaron;i histopatolo&scaron;ka reklasifikacija adenokarcinoma pluća na osnovu kriterijuma koje je postavila internacionalna asocijacija za proučavanje carcinoma pluća, američko torakalno dru&scaron;tvo i evropsko respiratorno dru&scaron;tvo; odredi ekspresija TTF-1 u adenokarcinomu pluća i povezanost sa EGFR mutacionim statusom; odredi učestalost, tip i povezanost EGFR mutacija sa predominantnim tipom adenokarcinoma i utvrdi da li bronhoskopska biopsija može da bude reprezentativni uzorak za određivanje EGFR mutacionog statusa. Histopatolo&scaron;ka građa adenokarcinoma pluća u hirur&scaron;kim uzorcima je heterogenija u odnosu na biopsijske uzorke i ta razlika je statistički značajna (p&lt;0,001). Acinarno predominantni tip je najzastupljeniji u hirur&scaron;kim i biopsijskim uzorcima bez statistički značajne razlike u raspodeli predominantnih tipova u njima (p=0,65883). Predominantni tip u primarnom tumoru određuje predominantni tip u limfogenim metastazama. EGFR mutacije tipa insercija na egzonu 21 i L858R mutacija na egzonu 20 su detektovane kod tri od 60 (5%) bolesnika u pet od 120 uzoraka (tri hirur&scaron;ka i dva biopsijska uzorka), če&scaron;će kod žena, starijih od 60 godina, pu&scaron;ača i u solidno predominantnom tipu. Ne postoji statistički značajna razlika u koncentraciji izolovane DNK između EGFR mutiranih i wt EGFR adenokarcinoma u biopsijskim (p=0,132) i hirur&scaron;kim uzorcima (p=0,641). Procenat invalidnih rezultata prilikom određivanja EGFR mutacionog statusa u je veći u biopsijskim uzorcima u odnosu na hirur&scaron;ke uzorke. Postoji statistički značajna razlika izmeĐu broja TTF-1 pozitivnih i TTF-1 negativnih adenokarcinoma (p&lt;0,001), ali ne i u raspodeli ovih bolesnika prema polovima (p=0,1231), prosečnoj starosti, pu&scaron;ačkim navikama (p=0,6488) i prosečnoj veličini tumora (p=0,21). Postoji pozitivna korelacija između TTF-1 pozitivne ekspresije i EGFR mutacionog statusa stoga TTF-1 pozitivna ekspresija može da bude prediktor pozitivnog EGFR mutacionog statusa. Bronhoskopska biopsija je reprezentativni uzorak za određivanje EGFR mutacionog statusa zato &scaron;to: većina dijagnostičkih biopsijskih uzoraka ima vi&scaron;e od 100 očuvanih tumorskih ćelija, nema razlike u raspodeli predominantnih tipova u odnosu na hirur&scaron;ke uzorke, EGFR mutacije se detektuju u uzorcima sa manje od 100 tumorskih ćelija i manje od 20% volumenske gustine tumorskog tkiva, razlika između koncentracije izolovane DNK u EGFR mutiranim i wt EGFR adenokarcinomima u biopsijskim i hirur&scaron;kim uzorcima nije statistički značajna (p=0,132 i p=0,641).</p> / <p>Epidermal growth factor receptor (EGFR) belongs to the family of protein-tyrosin kinase family, whose activation is associated with the proliferation of malignant cells, invasion, inhibition of apoptosis, tumor angiogenesis and metastatic spread and thus plays an important role in carcinogenesis and tumor progression. Activated mutations take place around the catalytic tyrosine kinase domain. Biopsy, cytological and surgical specimens are used for the detection of EGFR mutations at the time of diagnosis of adenocarcinoma or carcinoma with an adenocarcinoma component, most reliably using a polymerase chain reaction. The fact that the application of molecular tyrosin kinase inhibitor therapy to patients with EGFR mutated lung adenocarcinoma improves the prognosis of the disease, there is resistance in certain types of EGFR mutations and connection with histopathological and immunohistochemical characteristics of tumor, that the bronchoscopic specimen is often the only specimen in which it is necessary to determine the molecular profile of the tumor, the primary objective of this thesis is to determine the frequency and type of EGFR mutations and their connection with the characteristics of adenocarcinoma. In order to realize this objective, the following secondary objectives have been set: to execute histopathological reclassification of lung adenocarcinoma based on the criteria set by the International Association for the Study of Lung Cancer, the American Thoracic Society and European Respiratory Society; determine the expression of TTF-1 in lung adenocarcinoma and connection with EGFR mutation status; determine the frequency, type and connection of EGFR mutations with predominant type of adenocarcinoma and confirm whether bronchoscopic biopsy may be a representative specimen for the determination of EGFR mutation status. Histopathological material of lung adenocarcinoma in surgical specimens is more heterogeneous in relation to biopsy specimens and such difference is statistically significant (p&lt;0,001). Acinar predominant type is the most common in surgical and biopsy specimens with no statistically significant differences in the distribution of predominant type among them (p=0,65883). The predominant type in the primary tumor determines the predominant type in lymphatic metastases. EGFR mutations in the type of insertions on exon 21 and L858R mutations on exon 20 have been detected in three out of 60 (5%) of patients in five out of 120 specimens (three surgical and two biopsy samples), more often in women older than 60, smokers and in a solid predominant type. There are no statistically significant differences in the concentration of isolated DNA between EGFR mutated and wt EGFR adenocarcinoma in biopsy (p=0,132) and surgical specimens (p=0,641). The percentage of invalid results in determining the EGFR mutation status is higher in biopsy specimens compared to the surgical specimens. There is a statistically significant difference between the number of TTF-1 positive and TTF-1 negative adenocarcinoma (p&lt;0,001), but not in the distribution of these patients according to gender (p=0,1231), average age, smoking habits (p=0,6488) and average tumor size (p-0,21). There is a positive correlation between TTF-1 positive expression and EGFR mutation status and therefore TTF-1 positive expression can be a predictor of positive EGFR mutation status. Bronchoscopic biopsy is a representative sample for the determination of EGFR mutation status because: most diagnostic biopsy specimens have more than 100 preserved tumor cells, there is no difference in the distribution of predominant types in relation to surgical specimens, EGFR mutations are detected in samples with less than 100 tumor cells and less than 20% of volume density of tumor tissue, the difference between the concentration of isolated DNA in EGFR mutated and wt EGFR adenocarcinoma in biopsy and surgical specimens is not statistically significant (p=0,132 and p=0,641).</p>

<p>UVOD: Hipertenzivna oboljenja u trudnoći predstavljaju heterogenu grupu bolesti koja se javljaju kod 3-8% trudnica op&scaron;te populacije. Najteže forme ovih oboljenja preeklampsija, eklampsija i HELLP sindrom su vodeći uzročnici morbiditeta i mortaliteta majke i ploda u odnosu na sve druge komplikacije u trudnoći. Etiopatogeneza ovih oboljenja je jo&scaron; uvek nedovoljno razja&scaron;njena ali se smatra da placenta ima ključnu ulogu u nastanku ovih komplikacija, odnosno da placentalna insuficijencija, koja nastaje kao posledica nedovoljne adaptacije decidualnih i intramiometrijalnih delova spiralnih arterija već u prvih nekoliko nedelja trudnoće, dovodi do redukcije utero-placentalne cirkulacije i lokalne placentalne hipoksije, &scaron;to se nepovoljno održava i na majku i na plod. U cilju razja&scaron;njenja patofiziolo&scaron;kih mehanizama nastanka hipertenzivnih oboljenja u trudnoći i pronalaska dovoljno senzitivnih makera koji bi pomogli u ranom predviđanju nastanka najtežih formi ovih oboljenja, do sada su ispitivani brojni proteini koji učestvuju u procesima stvaranja i razvoja placentalne vaskularne mreže kao &scaron;to su vaskularni endotelni faktor rasta (VEGF-A), placentalni faktor rasta (PlGF) i solubilni receptor fms-like tirozin kinaza receptor (sFlt-1). CILJ: Uporediti serumske koncentracije (sFlt-1, PlGF, VEGF-A, PAPP-a, free&szlig;hCG, glukoze, ukupnog holesterola, HDL holesterola, LDL holesterola, triglicerida, apo-AI, apoB, AST, ALT, GGT, kreatinina, ureje, mokraćne kiseline, hsCRP, Na, K, Cl, P, Mg i Ca između grupe trudnica sa preeklampsijom, hroničnom i gestacijskom hipertenzijom i kontrolne grupe trudnica u prvom trimestru trudnoće između 11 i 14. nedelje gestacije. Ispitati da li se vrednosti odabranih laboratorijskih parametara (sFlt-1, VEGF-A i PLGF) kod ispitivanih trudnica statistički značajno razlikuju u odnosu na gestacijsku nedelju u trenutku porođaja, težinu i dužinu i APGAR skor bodovanja novorođenčeta. Ispitati da li se vrednosti angiogenih proteina:sFlt-1, VEGF-A, PlGF značajno razlikuju kod ispitivanih trudnica u odnosu na broj prethodnih trudnoća i starosti trudnica. MATERIJAL I METODE: Istraživanje je sprovedeno kao prospektivno analitička studija u Kliničkom centru Vojvodine, u periodu od juna 2012. do februara 2015. godine. U istraživanje je uključeno ukupno 143 trudnice starosti od 18 &ndash; 43 godine. Sve trudnice uključene u istraživanje podeljene su na dve ispitivane i jednu kontrolnu grupu. Prvu ispitivanu grupu činilo je 43 trudnice koje su po definisanim kriterijuma razvile preeklampsiju u aktuelnoj trudnoći. Drugu ispitivanu grupu činilo je 46 trudnica kojima je dijagnostikovana ili potvrđena hronična ili gestacijska hipertenzija u aktuelnoj trudnoći. Kontrolnu grupu činilo je 54 zdravih trudnica sa verifikovanim fiziolo&scaron;kim ishodom trudnoće u terminu, bez maternalnih i fetalnih komplikacija. Prilikom regrutovanja trudnica (između 11+0 i 13+6 nedelja gestacije) za uče&scaron;će u istraživanju, uzeti su anamnestički podaci o faktorima rizika za pojavu hipertenzivnih oboljenja u trudnoći, i u okviru kliničkog i aku&scaron;erskog pregleda urađena su antropometrijska merenja, merenje krvnog pritiska, i specijalizovani ultrazvučni pregled ploda radi utvrđivanja gestacijske starosti ploda i određivanja rizika za pojavu hromozomskih anomalija ploda. Trudnicama je nakon uzimanja anamnestičkih podataka i kliničkog i aku&scaron;erskog pregleda i potpisanog pisanog pristanka pacijenta o dobrovoljnom učestvovanju u istraživanju izvađena krv radi određivanja odabranih laboratorijskih parametara. Serumske koncentracije sFlt1, VEGF-A i PIGF određivane su kvantitativnom ELISA tehnikom (R&amp;D Systems Europe Ltd. Abingdon, UK), dok su: glukoza, ukupni holesterol, HDL holesterol, LDL holesterol, trigliceridi, apo-AI I apoB, AST, ALT, GGT, kreatinin, ureja, mokraćna kiselina, hsCRP, Na, K, Cl, Mg, P, Ca određivani na automatizovanim analizatorskim sistemima. Sve trudnice su kategorisane u 2 ispitivane i kontrolnu grupu na osnovu pojave ili isključenja hipertenzivnih oboljenja u aktuelnoj trudnoći. Statistička obrada podataka urađena je u statističkom programu STATISTICA 12 (StatSoft Inc.,Tulsa, OK, USA). Podaci su predstavljeni tabelarno i grafički, nivo statističe značajnosti p, je tumačen statistički značajnim ukoliko su vrednosti p&lt;0,05. REZULTATI: Vrednosti serumskih koncentracija sFlt-1 se statistički značajno razlikuju u sve tri grupe ispitanica i značajno su vi&scaron;e u grupama sa hipertenzivnim oboljenjima u odnosu na zdravu grupu ispitanica, p&lt;0,001. Serumske koncentracije VEGF-A su značajno niže u grupi trudnica sa preeklampsijom u odnosu na zdrave trudnice kontrolne grupe (p&lt;0,001), dok se nivoi serumskih koncentracija PlGF statistički značajno razlikuju između sve tri grupe trudnica tako da su najniže vrednosti uočene u grupi sa preeklampsijom (p&lt;0,001) u odnosu na preostale dve grupe ispitanica. Nije uočeno postojanje statistički značajne razlike u nivoima PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg), p&gt;0,05. Nivoi free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije sFlt-1 preko 865 pg/ml imaju senzitivnost od 93% i specifičnost od 81,5% u predviđanju nastanka preeklampsije, dok serumske koncentracije PlGF ispod 60 pg/ml senzitivnost od 88,4% i specifičnost od 79,6% u predviđanju pojave preeklampsije. Serumske koncentracije sFlt-1, VEGF-A i PlGF ne pokazuju statistički značajnu razliku u odnosu na godine života trudnice i broja prethodnih trudnoća p&gt;0,05. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na telesnu težinu novorođenčeta, tako da su niže vrednosti oba proteina detektovane u grupi novorođenčadi sa porođajnom težinom ispod 1500 gr. u odnosu na telesnu masu između 2800-3300 gr, p&lt;0,001. Takođe su nađene niže vrednosti sFlt-1 i PlGF u grupi trudnica koje su se porodile pre 33. nedelje gestacije u odnosu na nedelju gestacije u trenutku porođaja preko 37 nedelje gestacije, p&lt;0,001. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na indeks telesne mase majke tako da su vi&scaron;e vrednosti sFlt-1 i niže vednosti PlGF nađene u grupi trudnica sa indeksom telesne mase ispod 25 u odnosu na grupu trudnica sa indeksom telesne mase preko 30 kg/m2, p&lt;0,001. Serumske koncentracije sFlt-1 u prvom trimestru trudnoće su značajno povezane sa parametrima inflamacije (hsCRP), vrednostima dijastolnog krvnog pritiska i nivoima free &szlig;hCG. Takođe se uočava značajna povezanost koncentracije PlGF sa indeksom telesne mase, vrednostima sistolnog krvnog pritiska i koncentracijom hsCRP u prvom trimestru trudnoće. ZAKLJUČAK: Nivoi antiangiogenog proteina sFlt-1 su vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Nivoi proangiogenog proteina VEGF-A su značajno niže u grupi trudnica sa preeklampsijom i hroničnom i gestacijskom hipertenzijom u odnosu na grupu trudnica bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije proangiogenog proteina PlGF su niže u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Serumske koncentracije placentalnog proteina free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Između trudnica sa hipertenzivnim poremećajima u trudnoći i zdravih trudnica nije uočeno postojanje značajne razlike u vrednostima placentalnog proteina PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg). Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na gestacijsku starost na porođaju i telesnu masu novorođenčeta i niže su kod trudnica koje su se prevremeno porodile kao i kod novorođenčati sa manjom porođajnom težinom. Serumske koncentracije sFlt-1 se značajno razlikuju u odnosu telesnu dužinu i APGAR skor novorođenčeta, tako da su vi&scaron;e vrednosti sFlt-1 udružene sa većom telesnom dužinom novorođenčeta i boljim APGAR skorom. Serumske koncentracije sFlt-1, VEGF-A i PlGF se ne razlikuju značajno u odnosu na godine života trudnice i broja prethodnih trudnoća. Nivoi proteina angiogeneze sFlt-1 i PlGF predstavljaju dobre prediktore u predviđanju nastanka preeklampsije u prvom trimestru trudnoće.</p> / <p>INTRODUCTION: Hypertensive disorders in pregnancy are a heterogeneous group of diseases that occur in 3-8% of all pregnancies. The most difficult forms of these diseases: preeclampsia, eclampsia and HELLP syndrome are the leading causes of maternal and fetal morbidity and mortality in relation to all other pregnancy complications. Etiopathogenesis of these diseases is still insufficiently understood but it is thought that the placenta plays a key role in the development of these complications, and that placental insufficiency, which occurs as a result of insufficient adaptation of decidual intramiometrial and parts of the spiral arteries in the first few weeks of pregnancy, leading to a reduction of utero- placental circulation and local placental hypoxia, which adversely affects the mother and the fetus. In order to elucidate the pathophysiological mechanisms of hypertensive disorders in pregnancy and to find sufficiently sensitive makers for early prediction of the most severe forms of these diseases, so far have been investigated a number of proteins involved in the processes of creation and development of placental vascular network such as vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and soluble fms-like receptor tyrosine kinase receptor (sFlt-1). OBJECTIVE: The aim of the study was to compare serum concentration of sFlt-1, PlGF, VEGF-A, PAPP-A, free&szlig;hCG, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg and Ca between the group of pregnant women with preeclampsia, chronic and gestational hypertension and the control group of pregnant women in the first trimester of pregnancy between 11 and 14 weeks gestation. Also the aim was to examine whether the value of selected laboratory parameters (sFlt-1, VEGF-A and PlGF) differ in relation to gestational week at the time of birth, weight, length and APGAR scoring system of newborns. The aim was to examine whether the value of angiogenic proteins: sFlt-1, VEGF-A and PlGF differ significantly in relation to the number of previous pregnancies and age of the pregnant woman. MATERIALS AND METHODS: The study was conducted as a prospective analytical study in the Clinical Center of Vojvodina, in the period from June 2012 to February 2015. The study included a total of 143 pregnant women aged 18 - 43 years. All pregnant women included in the study were divided into two study and one control group. The first study group consisted of 43 pregnant women who developed preeclampsia during the current pregnancy. The second study group consisted of 46 pregnant women who are newly diagnosed or confirmed chronic or gestational hypertension during the current pregnancy. The control group consisted of 54 healthy pregnant women with verified physiological outcome of pregnancy at term without maternal and fetal complications. Patients were included in the study between 11 + 0 and 13 + 6 weeks of gestation. All patients had data about risk factors for developing hypertensive disorders in pregnancy. After clinical and obstetric examination all patients underwent anthropometric measurements, measurement of blood pressure, and specialized ultrasound examination to determine precise gestational age of the fetus and to determine the risk for fetal chromosomal abnormalities. All patients signed a written consent of the patient&#39;s voluntary participation in the study. Serum levels of sFlt1, VEGF-A and PlGF were determined by quantitative ELISA (R &amp; D Systems Europe Ltd., Abingdon, UK), while glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg, Ca were determined on automated analyzer systems. All pregnant women were categorized into 2 study and a control group on the basis of presence of hypertensive disorders in the current pregnancy. Statistical analysis was performed in 12 statistical program STATISTICA (StatSoft Inc., Tulsa, OK, USA). The data are presented in tables and graphs, the level of significance p is interpreted statistically significant if the p value was less than &lt;0.05. RESULTS: Serum concentrations of sFlt-1 are statistically significantly different in all study groups and significantly higher in the groups with hypertensive disorders compared to healthy subjects p &lt;0.001. Serum levels of VEGF-A are significantly lower in the preeclampsia group compared to healthy control group (p &lt;0.001), while the levels of serum concentration of PlGF statistically significantly different between all groups so that the lowest values are observed in the preeclampsia group (p &lt;0.001) compared to the other two study groups. There is no statistically significant differences in the levels of PAPP-A, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca), p&gt; 0.05. Levels of free &szlig;hCG and HDL cholesterol levels are significantly lower, while the value of hsCRP and triglycerides significantly higher in the group of women with preeclampsia compared to the healthy control group. Serum concentrations of sFlt-1 over 865 pg/ml have a sensitivity of 93% and specificity of 81.5% in predicting preeclampsia, while serum PlGF concentration below 60 pg/ml, a sensitivity of 88.4% and a specificity of 79.6% in predicting preeclampsia. Serum concentrations of sFlt-1, VEGF-A and PlGF do not show a statistically significant difference compared to the age of pregnant women and the number of previous pregnancies p&gt; 0.05. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the weight of the newborn, so that the lower values of both proteins are in the group of infants with birth weight below 1500 gr. in relation to the body weight between 2800-3300 gr., p &lt;0.001. There is also lower concentrations of sFlt-1 and PlGF in a group with deliveries before 33 weeks of gestation compared to the deliveries after 37 week of gestation, p &lt;0.001. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the mother&#39;s body mass index so that the lower values of sFlt-1 and PlGF are in the group of women with a body mass index below 25 in relation to a group with a body mass index over 30 kg/m2, p &lt;0.001. Serum concentrations of sFlt-1 in the first trimester of pregnancy were significantly associated with the parameters of inflammation (hsCRP), diastolic blood pressure and levels of free &szlig;hCG. It is also observed a significant correlation between PlGF with a body mass index, systolic blood pressure and hsCRP concentration in the first trimester of pregnancy. CONCLUSION: The levels of anti-angiogenic protein sFlt-1 are higher in the group of pregnant women with preeclampsia than in the group with chronic and gestational hypertension and the control healthy group. Levels of proangiogenic VEGF-A protein are significantly lower in the preeclampsia group and group with gestational and chronic hypertension compared to the control group. Serum levels of proangiogenic PlGF protein are significantly lower in the preeclampsia group than in the group with chronic and gestational hypertension and the control group. Serum concentrations of placental protein free &szlig;hCG and HDL cholesterol are significantly lower, while the value of hsCRP and triglycerides significantly higher in the preeclampsia group compared to the control group. Among pregnant women with hypertensive disorders in pregnancy and healthy pregnant women there are no significant differences in the values of placental PAPP-A protein, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca). Serum concentrations of sFlt-1 and PlGF are significantly different in relation to gestational age at delivery and newborn body weight and are lower in group with preterm delivery and newborns with lower birth weight. Serum concentrations of sFlt-1 are significantly different compared to body length and Apgar score, so that the higher values of sFlt-1 are associated with better outcome of newborns (greater body length and better APGAR score). Serum concentrations of sFlt-1, VEGF-A and PlGF are not different significantly with respect to age of pregnancy and the number of previous pregnancies. The levels of sFlt-1 and PlGF represents helpful markers in prediction of preeclampsia in the first trimester of pregnancy.</p>

<p>Cilj: Svrha ovog istraživanja je da se odredi uticaj promena u funkciji, morfologiji i geometriji leve komore (LK) i odusustva očuvanog dnevno-noćnog profila krvnog pritiska (KP) na intrauterini zastoj u rastu fetusa (IUGR) i preterminsko zavr&scaron;avanje trudnoće kod gestacijske hipertenzije (GH), reverzibilnost tih promena posle porođaja i povezanost GH sa prisustvom arterijske hipertenzije u porodici. Metodologija: U ovu studiju, koja je koncipirana kao prospektivna, uključeno je 90 trudnica, 30 normotenzivnih, 30 sa GH i dipping profilom KP i 30 sa GH i non-dipping profilom KP. Svim ispitanicama urađen je kompletan dvo-dimenzionalni, pulsni i tkivni Doppler ehokardiografski pregled i ambulatorni 24-h monitoring KP u trećem trimestru trudnoće i 6 nedelja posle porođaja. Rezultati i diskusija: U grupi trudnica sa GH značajno vi&scaron;e su bili poremećeni parametri sistolne, dijastolne i globalne funkcije (EF, s&rsquo;, E, A, E/A, E/e&rsquo;, DTE, IVRT, IVCT, ET, Tei indeks, CO, CW, Ees), morfologije (IVSd, PLWd, RWT, masa miokarda, p&lt;0,0005) i geometrije LK (abnormalna geometrija 67,7% vs 3,3% kod normotenzivnih, p&lt;0,0005). Najizraženije promene bile su u podgrupi non-dippera. Posle porođaja registrovano je značajno popravljanje svih promenjenih ehokardiografskih parametara, a 96,7% ispitanica iz non-dipper podgrupe imale su očuvan dnevno-noćni ritam posle porođaja. U grupi sa GH utvrđeno je postojanje arterijske hipertenzije u porodici u 80% slučajeva u odnosu na 26,7% u kontrolnoj grupi (p&lt;0,0005). Analizom rezultata utvrđeno je da su povećanje maksimalne vrednosti noćnog dijastolnog KP, indeksa mase miokarda i totalne vaskularne rezistence nezavisni prediktori IUGR-a, dok su povećanje prosečne vrednosti noćnog sistolnog KP i indeksa mase miokarda i smanjenje EF nezavisni prediktori preterminskog porođaja. Zaključak: Promene u funkciji i morfologiji leve komore i non-dipping profil KP kod GH imaju prognostički uticaj na pojavu IUGR-a i preterminsko zavr&scaron;avanje trudnoće.</p> / <p>Objective: The purpose of this study was to determine the influence of changes in function, morphology, and geometry of the left ventricle (LV) and a non-dipping arterial blood pressure (BP) pattern on the intrauterine growth restriction (IUGR) and preterm delivery in pregnant women with gestational hypertension (GH), reversibility of these changes after delivery and connection between BP in family with GH. Methods: This prospective study included 90 pregnant women, 30 normotensive, 30 with GH and dipping BP pattern and 30 with GH and non-dipping BP pattern. All participants underwent a complete two-dimensional, pulsed and tissue Doppler echocardiography and 24-h ambulatory blood pressure monitoring in the third trimester and 6 weeks after delivery. Results and discussion: Participants with GH had more impaired parameters of the LV systolic, diastolic and global function (EF, s&rsquo;, E, A, E/A, E/e&rsquo;, DTE, IVRT, IVCT, ET, Tei index, CO, CW, Ees), morphology (IVSd, PLWd, RWT, myocardial mass, p&lt;0,0005) and geometry (abnormal geometry 67,7% vs 3,3% in normotensive, p&lt;0,0005). The greatest changes were noticed in non-dippers. All changed echocardiographic parameters became improved, while 96,7 % non-dipper participants became dipper after delivery. Arterial hypertension in family was present in 80% women with GH vs 26,7% in normotensive (p&lt;0,0005). Analyses revealed that maximum night-time diastolic BP, mass index and total vascular resistance were identified as independent predictors of IUGR. Average systolic night-time BP, mass index and EF were identified as independent predictors of preterm delivery. Conclusion: Changes in LV function, morphology and geometry and a non-dipping pattern of BP in GH predicts IUGR and preterm delivery.</p>