Læknablaðið : fylgirit - 03.01.2017, Blaðsíða 40

X V I I I V Í S I N D A R Á Ð S T E F N A H Í
F Y L G I R I T 9 1
40 LÆKNAblaðið/Fylgirit 91 2017/103
(WT) and Mitf mi-vga9/mi-vga9 (MUT) mice for primary neruonal cult-
ure. Projection neurons were selected based on morphology and size for
whole-cell patch clamping to assess changes in membrane currents and
spiking activity.
Results: Voltage clamp data shows that the MUT OBPNs peak A-Type
current magnitude is reduced to about half of their WT counterpart. The
reversal potential is also shifted by about 10 mV in the positive direction.
Current clamp data recorded under passive conditions showed a four-
-fold increase in the MUT OBPNs firing frequency whilst a 110 pA current
pulse from ~70mV evoked spike trains which had a 2.11 times shorter
response time, with a 1.35 fold increase in firing frequency, implying a
decreased A-Type current.
Conclusions:The MUT OBPNs show a reduced A-Type current, which
results in a faster firing frequency and shorter response time to current
injections. The MUT IV curve shift suggests a reduction in ion channels
mediating positive outward current. This change in OBPN sensitivity may
explain the increased olfactory discrimination of Mitf mutant mice
E 109 A rare germline coding variant affects ATG7 function
Margrét H. Ögmundsdóttir1, Valerie Fock1, Kristín Bergsteinsdóttir1, Vivian
Pogenberg2, Ramile Dilshat1, Sigrún Kristjánsdóttir3, Christian Bindesboll4, Einar
S. Björnsson5, Anne Simonsen4, Matthias Wilmanns2, Jón G. Jónasson3, Eiríkur
Steingrímsson1
1Biomedical Center, Department of Medicine, University of Iceland, 2EMBL Hamburg,
3Department of Pathology, Landspítali-University Hospital, 4Institute of Basic Medical Sciences,
University of Oslo, 5Department of Gastroenterology and Hepatology, Landspitali-University
Hospital
mho@hi.is
Introduction: Autophagy is an intracellular degradation process
which can be beneficial for cancer cells under challenging conditions.
However, mouse studies suggest that autophagy may protect against
tumor initiation, especially in the liver. Whether key autophagy genes
also play a role in cancer initiation in humans has been unclear.
Materials and Methods: Genetic association analysis of patients with
hepatocellular and bile duct cancer were employed for analyzing
whether variants in key autophagy genes associate with these types
of cancer. Tumor tissue samples were analyzed and hepatocellular cell
cultures and mouse embryonic fibroblasts were utilized for functional
experiments.
Results: Through genetic association analysis of patients with
hepatocellular and bile duct cancer, we identified a rare germline
missense variant in the essential autophagy gene ATG7. The autophagy
substrate p62 accumulates more in tumors of carriers than non-carriers.
We identified two ATG7 isoforms expressed in the liver, one of which
lacks the ability to promote autophagosome formation through lipi-
dation of the core autophagy protein LC3. Expression of the variant in
both ATG7 isoforms leads to altered protein function in vitro.
Discussions: Our data indicate a role of ATG7 in the development of
human cancer and demonstrate important functional properties of
ATG7.
E 110 Effects of thrombin and activated protein C on endothelium.
Role of AMP-kinase and biased signaling
Sigurður T. Karvelsson1, Hallbera Guðmundsdóttir1, Haraldur Halldórsson1,
Guðmundur Þorgeirsson2
1Inst. Pharmacol. Toxicol, University of Iceland, 2Department of Medicine, University of Iceland
stk13@hi.is
Introduction: Some receptors can be activated by different ligands
leading to different cellular responses, so-called biased signaling. The
PAR1 receptor can be activated by both thrombin and activated protein
C (APC). In endothelial cells, thrombin has barrier disruptive and in-
flammatory effects while APC mediates barrier enhancement and reduces
inflammation. Our aim is to define the differences in signaling following
activation of PAR1 in cultured endothelial cells by thrombin and APC,
particularly to examine the role of AMP-activated kinase (AMPK) in
mediating the anti-inflammatory effects of APC.
Materials and methods: Human umbilical vein endothelial cells were
grown in EGM medium and used at passage 2-3. Expression of adhesion
molecules (ICAM, VCAM and selectin) was studied using qPCR and
western blotting. Phosphorylation of Akt, AMPK, myosin light chain
(MLC) and MAPkinases was determined by western blotting.
Results: Thrombin (1u/ml) caused immediate but transient activation
of AMPK, Erk1/2 and p38 and a slower activation of JNK, as well as an
immediate inhibition of Akt. Thrombin also caused increased phosphor-
ylation of MLC and increased expression of adhesion molecules. APC
caused all the same effects, but to a much lesser degree. Pretreatment
with APC or with a low dose of thrombin reduced the response to a high
dose of thrombin. Pretreatment with activators of AMPK also reduced the
response to thrombin as did treatment with inhibitors of p38 and JNK.
Conclusions: These result are more compatible with APC having
preconditioning effects partly mediated by AMPK, rather than causing
biased signaling.
E 111 Útgjöld íslenskra heimila vegna heilbrigðismála
Rúnar Vilhjálmsson
Hjúkrunarfræðideild, Háskóli Íslands
runarv@hi.is
Inngangur: Heilbrigðisútgjöld heimila geta haft veruleg áhrif á aðgengi að
heilbrigðisþjónustu. Markmið rannsóknarinnar var að kanna heilbrigðis-
útgjöld heimilanna og hvort tilteknir hópar verðu hærri upphæðum og
hefðu meiri kostnaðarbyrði en aðrir.
Efniviður og aðferðir: Byggt er á landskönnuninni Heilbrigði og lífshættir
Íslendinga, sem fram fór vorið 2015 meðal þjóðskrárúrtaks Íslendinga á
aldrinum 18-75 ára. Svarendur fengu póstsendan spurningalista en var
einnig gefinn kostur á að fylla spurningalistann út á netinu. Alls tóku
tæplega 1600 (N=1599) einstaklingar þátt í heilbrigðiskönnuninni og voru
heimtur tæp 60%. Meðal annars var spurt um sundurliðaðan kostnað
heimilis vegna heilbrigðismála, auk ítarlegra bakgrunnsspurninga.
Niðurstöður: Mikill munur var á heilbrigðisútgjöldum heimilis eftir
hópum. Hæst útgjöld í krónum höfðu heimili miðaldra og eldra fólks,
sambúðarfólks, stórra fjölskyldna, fólks með hærri tekjur, langveikra og
öryrkja. Þegar heimilisútgjöld vegna heilbrigðismála voru hins vegar
skoðuð sem hlutfall af ráðstöfunartekjum heimilis kom í ljós að útgjalda-
byrði var hæst á heimilum ungs fólks og námsmanna, atvinnulausra, fólks
utan vinnumarkaðar, lágtekjufólks, langveikra og öryrkja.
Ályktanir: Félagsleg heilbrigðiskerfi miða að því að halda niðri heil-
brigðisútgjöldum heimila til að tryggja gott aðgengi að heilbrigðisþjón-
ustu. Há heilbrigðisútgjöld og útgjaldabyrði ýmissa hópa hérlendis er
verulegt áhyggjuefni. Vinna þarf markvisst að því að draga úr heildarút-
gjöldum einstaklinga og heimila vegna heilbrigðismála og treysta um leið
stoðir hins félagslega heilbrigðiskerfis Íslendinga.