{"id":5958,"date":"2026-10-19T09:48:14","date_gmt":"2026-10-19T09:48:14","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lyfjafraedi-tijana-drobnjak\/"},"modified":"2026-10-19T09:48:14","modified_gmt":"2026-10-19T09:48:14","slug":"doktorsvorn-i-lyfjafraedi-tijana-drobnjak","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lyfjafraedi-tijana-drobnjak\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed lyfjafr\u00e6\u00f0i – Tijana Drobnjak"},"content":{"rendered":"
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\u00deri\u00f0judaginn 4. desember ver Tijana Drobnjak doktorsritger\u00f0 s\u00edna \u00ed lyfjafr\u00e6\u00f0i vi\u00f0 Lyfjafr\u00e6\u00f0ideild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: L\u00edfe\u00f0lisfr\u00e6\u00f0ilegir og lyfjahvarfafr\u00e6\u00f0ilegir eiginleikar fylgjupr\u00f3teins 13 (PP13). In vitro og in vivo d\u00fdratilraunir. Physiological and pharmacokinetic properties of placental protein 13 (PP13). In vitro and in vivo animal studies.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Harvey Kliman, pr\u00f3fessor vi\u00f0 Yale Medical University, og Alexander Kristinn Sm\u00e1rason, pr\u00f3fessor vi\u00f0 H\u00e1sk\u00f3lann \u00e1 Akureyri.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var dr. Sveinbj\u00f6rn Gizurarson, pr\u00f3fessor vi\u00f0 lyfjafr\u00e6\u00f0ideild og me\u00f0lei\u00f0beinandi var dr. Hamutal Meiri, pr\u00f3fessor og verkefnastj\u00f3ri \u00ed \u00cdsrael. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd El\u00edn Soff\u00eda \u00d3lafsd\u00f3ttir, pr\u00f3fessor vi\u00f0 Lyfjafr\u00e6\u00f0ideild, Reynir T\u00f3mas Geirsson, pr\u00f3fessor emeritus vi\u00f0 L\u00e6knadeild, og Hildur Har\u00f0ard\u00f3ttir, d\u00f3sent vi\u00f0 L\u00e6knadeild.<\/p>\n

H\u00e1kon Hrafn Sigur\u00f0sson, pr\u00f3fessor og deildarforseti vi\u00f0 Lyfjafr\u00e6\u00f0ideild H\u00e1sk\u00f3la \u00cdslands, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13:00.<\/p>\n

\u00c1grip af ranns\u00f3kn <\/strong><\/p>\n

Markmi\u00f0 doktorsverkefnisins var 1) a\u00f0 sko\u00f0a skammt\u00edma- og langt\u00edma\u00e1hrif pr\u00f3teins \u00e1 \u00e6\u00f0akerfi\u00f0 \u00ed kringum legi\u00f0. 2) A\u00f0 skilgreina verkunarm\u00e1ta pr\u00f3teinsins \u00e1 einangra\u00f0ar leg\u00e6\u00f0ar \u00far rottum. 3) A\u00f0 meta \u00e1hrif pr\u00f3teinsins \u00e1 \u00e6\u00f0akerfi\u00f0 \u00ed kringum legi\u00f0 og f\u00f3sturv\u00f6xt \u00ed rottum. 4) A\u00f0 meta lyfjahv\u00f6rf pr\u00f3teinsins \u00ed kan\u00ednum. Osm\u00f3t\u00edskar d\u00e6lur voru \u00edgr\u00e6ddar \u00ed \u00f3\u00feunga\u00f0ar rottur sem losu\u00f0u um 10 \u00b5l\/klst og t\u00e6mdu sig \u00e1 sj\u00f6 d\u00f6gum. \u00deverm\u00e1l slag- og bl\u00e1\u00e6\u00f0a \u00far legi voru borin saman \u00e1 milli h\u00f3pa. Til a\u00f0 skilgreina verkunarh\u00e1tt fylgjupr\u00f3teins 13, voru legslag\u00e6\u00f0ar einangra\u00f0ar og settar \u00ed s\u00e9rh\u00e6f\u00f0an \u00e6\u00f0am\u00e6li (e. arteriograph). Pr\u00f3teini\u00f0 reyndist hafa \u00e6\u00f0av\u00edkkandi \u00e1hrif (38-50%) sem h\u00e6gt var a\u00f0 hemja me\u00f0 \u00fev\u00ed a\u00f0 hinda a\u00f0gengi niturox\u00ed\u00f0s og arak\u00edd\u00f3ns\u00fdru. \u00c1hrif pr\u00f3teinsins \u00ed \u00feungu\u00f0um rottum me\u00f0 \u00edgr\u00e6ddar osm\u00f3t\u00edskar d\u00e6lur sem fengu niturox\u00ed\u00f0hindra \u00ed drykkjarvatni leiddi \u00ed lj\u00f3s markt\u00e6kt minni unga samanbori\u00f0 vi\u00f0 vi\u00f0mi\u00f0unarh\u00f3pinn. Lyfjahv\u00f6rf fylgjupr\u00f3teins 13, sem f\u00f3ru fram \u00ed kan\u00ednum, voru sko\u00f0u\u00f0 me\u00f0 \u00fev\u00ed a\u00f0 gefa \u00ferj\u00e1 mismunandi styrki af pr\u00f3teininu (5 ng\/mL, 10 ng\/mL og 50 ng\/mL) \u00ed \u00e6\u00f0 (I.V.), og s\u00ed\u00f0an einn styrkur (50 ng\/mL) var gefinn undir h\u00fa\u00f0 (S.C.). \u00cd lj\u00f3s kom a\u00f0 b\u00e6\u00f0i dreifir\u00famm\u00e1l og flatarm\u00e1li\u00f0 undir ferlinum (AUC) reyndust vera skammtah\u00e1\u00f0 milli I.V. h\u00f3panna.<\/p>\n

Ni\u00f0urst\u00f6\u00f0urnar s\u00fdndu a\u00f0 fylgjupr\u00f3tein 13 hefur veruleg \u00e6\u00f0av\u00edkkandi \u00e1hrif, sem jafnframt hefur j\u00e1kv\u00e6\u00f0 \u00e1hrif \u00e1 v\u00f6xt fylgju og f\u00f3sturs. Ni\u00f0urst\u00f6\u00f0urnar eru mikil hvatning fyrir \u00e1framhaldandi ranns\u00f3knum til a\u00f0 meta fylgjupr\u00f3tein 13 sem m\u00f6gulegan lyfjasprota til a\u00f0 fyrirbyggja me\u00f0g\u00f6ngueitrun og a\u00f0ra me\u00f0g\u00f6ngutenda sj\u00fakd\u00f3ma sem tengjast \u00f3fulln\u00e6gjandi bl\u00f3\u00f0fl\u00e6\u00f0i til legs og fylgju.<\/p>\n

Abstract <\/strong><\/p>\n

The aim of this Ph.D. was \u00a0to study 1) long and short term effects, and evaluate overall effect of PP13 exposure on uterine vasculature, and the fetal outcome in rats. \u00a02) To define the mechanism of action in isolated rat arteries in vitro. 3) To evaluate the pharmacokinetic profile of PP13 in rabbits. Slow-release osmotic pums were implanted in non-pregnt rats, releasing its content for seven days. The diameter of arteries and veins were compared between groups, resulting in significant vascular expansion of all vessels in rPP13 group. To study the mechanism of action uterine vessels were isolated and cannulated in arteriograph. rPP13 elicited 38-50% arterial vasodilation mediated via endothelial signaling pathways of nitric oxide (NO) and arachidonic acid. In vivo inhibition of NO showed that rPP13 treated animals had heavier pups and bigger placentas, in comparison to the control. In order to establish pharmacokinetic profile of PP13, three different concentrations of the protein (5 ng\/mL, 10 ng\/mL and 50 ng\/mL) were administrated intravenously and one concentration (50 ng\/mL) was administrated subcutaneously. The results indicate that PP13 is a potent vasodilator, has a positive effect on fetal growth and may be a key factor in preconditioning the uterine vasculature. In addition pharmacokinetic studies indicate that the concentration of total PP13 released into maternal circulation may be much higher than previously estimated. Further studies are required in order to get an insight into the effect on human vasculature, however, these results encourage evaluation of PP13 as a potential therapeutic agent for obstetric syndromes characterized by insufficient uteroplacental blood flow.\u00a0<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Tijana Drobnjak er f\u00e6dd \u00e1ri\u00f0 1987 \u00ed Serb\u00edu, en flutti til \u00cdslands \u00e1samt fj\u00f6lskyldu sinni \u00e1ri\u00f0 2001. H\u00fan lauk st\u00fadentspr\u00f3fi af n\u00e1tt\u00farufr\u00e6\u00f0ibraut Kvennask\u00f3lans \u00ed Reykjav\u00edk \u00e1ri\u00f0 2008, BS-pr\u00f3fi \u00ed lyfjafr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2011 og MS-pr\u00f3fi fr\u00e1 sama sk\u00f3la \u00e1ri\u00f0 2013. Me\u00f0fram doktorsn\u00e1mi hefur h\u00fan starfa\u00f0 sem stundakennari vi\u00f0 H\u00e1sk\u00f3la \u00cdslands og fr\u00e1 \u00e1rinu 2016 sem v\u00edsindama\u00f0ur \u00fer\u00f3unardeildar \u00ed Alvotech. Tijana er d\u00f3ttir Slavisa Drobnjak, i\u00f0na\u00f0armanns, og Ljilj\u00f6nu Drobnjak, lyfjat\u00e6knis.<\/p>\n<\/div><\/div>","protected":false},"featured_media":1103,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2018-12-04T13:00:00+00:00","_phd_date_end":"2018-12-04T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"L\u00edfe\u00f0lisfr\u00e6\u00f0ilegir og lyfjahvarfafr\u00e6\u00f0ilegir eiginleikar fylgjupr\u00f3teins 13 (PP13). In vitro og in vivo d\u00fdratilraunir. Physiological and pharmacokinetic properties of placental protein 13 (PP13). 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