Læknablaðið : fylgirit - 03.01.2017, Blaðsíða 22

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
22 LÆKNAblaðið/Fylgirit 91 2017/103
observed positive association between low 25-OHD and lung cancer (HR
= 1.72, 95% CI: 1.02-2.87).
Conclusions: Our data suggest that higher pre-diagnostic serum 25-OHD
levels may be associated with improved survival for cancer patients.
Further studies are needed to rule out the potential effect of preclinical
disease on vitamin D levels (reverse causation).
E 48 Propensity score analysis of coronary artery calcium by
hormone replacement therapy: The AGES-Reykjavik Study
Thor Aspelund1, Aðalsteinn Guðmundsson1, Gunnar Sigurðsson2, Vilmundur
Guðnason1, Helgi Jónsson1
1Medicine, University of Iceland, 2Research Institute, Icelandic Heart Association
thor@hi.is
Introduction: The long term effect of postmenopausal hormone
replacement therapy (HRT) on atherosclerosis and cardiovascular health
is controversial. Coronary Artery Calcium (CAC) is an established marker
of atherosclerotic plaque burden. The objective was to assess the relations-
hip between HRT and CAC.
Methods: Cross sectional assessment in population based AGES-
Reykjavik of the Icelandic Heart Association. Participants were 2867
women (mean age 76±5 years) who had completed questionnaires on
HRT use. The measurement of CAC by Computed Tomography was used
as outcome variable and compared between women with history of HRT
or had never used HRT. Propensity score analysis based on midlife data
was used to adjust for possible confounding.
Results: 872 (30.4%) of the 2867 participants had used HRT and 312
(10.9%) were current users. After adjustment for age, other late life
variables, and a propensity score based on midlife data for HRT use as
observed in late life, the CAC showed significant negative associations
with history and length of HRT use. This association was evident in all
age categories. When the duration of HRT use was more than 15 years,
the median coronary calcium was less than 50% of that observed in never
users. The lowest CAC was observed in those who started HRT within
five years after menopause.
Conclusion: Long term HRT shows a strong association with lower CAC
in comparison with women who had never used HRT. The negative
association between HRT and CAC was evident in all age groups of older
women.
E 49 Brain activities of an Alzheimer's disease drug, is galanthamine
a dual-active medication?
Natalia Kowal1, Philip K. Ahring2, Dinesh Indurthi2, Mary Chebib2, Thomas Balle2,
Elín S. Ólafsdóttir3
1Pharmacy, HAGI, Faculty of Pharmaceutical Sciences, 2Faculty of Pharmacy, The University of
Sydney, 3Faculty of Pharmaceutical Sciences, University of Iceland
nmp@hi.is
Introduction: Galanthamine, a plant alkaloid isolated from snowdrop
(Galanthus sp.), is approved as a drug for treatment of mild-to-moderate
Alzheimer’s disease. Galanthamine works primarily as an acetylcholine-
sterase inhibitor but it is also commonly referred to as a positive allosteric
modulator (PAM) of neuronal α7 and α4β2 subtypes of the nicotinic
acetylcholine receptor (nAChR). Previous experiments reported to show
nAChR PAM activity were primarily conducted on rat hippocampal
neurons, PC12 cells naturally expressing different nAChRs and on the
receptors expressed in HEK cells. Data available from receptors expressed
in Xenopus oocytes are limited and show marginal PAM activity.
Methods: Different subtypes and stoichiometries of human neuronal
nAChRs were expressed in Xenopus oocytes. Electrophysiological cur-
rents evoked by ACh alone or in combination with galanthamine were
recorded using two electrode voltage clamp.
Results: In our hands, galanthamine was unable to produce significant
PAM responses when tested on α7 and individual stoichiometries of α4β2
and α4β4 nAChRs expressed in Xenopus oocytes. However, in agreement
with the literature we observed inhibition of ACh-evoked responses at
high concentrations (10 – 100 µM range).
Conclusions: Our results therefore question the perception of galant-
hamine as a nAChR PAM.
E 50 Isolation of exosomes from cell culture media using different
precipitation methods
Berglind E. Benediktsdóttir, Björg S. Kristjánsdóttir
Faculty of Pharmaceutical Sciences, University of Iceland
bergline@hi.is
Introduction: Exosomes offer many advantages as nanocarriers for drug
delivery due to their size, stability and selectivity. One crucial factor for
their use as nanocarriers in the clinical setting is a robust method for
exosome isolation. Currently, a method has yet to be developed that
results in efficient isolation of pure exosomes in high yield. Therefore, the
first steps in identifying an applicable method was to determine the suita-
bility of different precipitation methods for exosome isolation.
Materials and methods: Three cell lines, immortalized basal cell line
BCI-N.1.1 and cancer cell lines A549 and D492, were used. Five different
precipitation methods, based on the use of precipitation fluid (ExoQuick
or ExoSpin) were studied with various changes such as centrifugation filt-
ers, different centrifugation speed and different ratio of precipitation fluid
and cell culture medium. The isolated particles were then analyzed with
dynamic light scattering (DLS) and transmission electron microscopy
(TEM).
Results: Only one method, based on the use of ExoQuick used as instruct-
ed from the manufacturer, resulted in a visible precipitation from the BCI-
N.1.1 cell culture medium. Particle size was 122-578 nm when measured
with DLS and 50-80 nm when measured with TEM which is in line with
the diameter of exosomes (40-120 nm). Other methods did not result in
visible precipitations.
Conclusions: Methods based on exosome precipitation are not as robust
as previously anticipated and there is clearly a need for further optim-
ization. Alternatively, other isolation methods such as size-exclusion
chromatography might be more suitable to isolate exosomes in more
quantity.
E 51 Monitoring of Allopurinol Therapy in Patients with APRT
Deficiency, Utilizing UPLC-MS/MS Assay
Unnur A. Þorsteinsdóttir1, Finnur F. Eiríksson1, Hrafnhildur L. Runólfsdóttir2, Viðar
Ö. Eðvarðsson3, Runólfur Pálsson3, Margrét Þorsteinsdóttir1
1Faculty of Pharmaceutical Sciences, University of Iceland, 2Faculty of Medicine, University of
Iceland, 3Landspítali - The National University Hospital of Iceland
uth15@hi.is
Introduction: Adenine phosphoribosyltransferase (APRT) deficiency
results in excessive urinary excretion of the poorly soluble 2,8-dihydroxya-
denine (DHA), causing nephrolithiasis and chronic kidney disease.