Docstoc

2nd Annual Meeting Program

Document Sample
2nd Annual Meeting Program Powered By Docstoc
					  2nd Annual Meeting


          Pharmacodynamics
          Pharmacogenomics
            Drugs for obesity




            Program



    20. januar 2010, kl. 10.00 – 21.00


Syddansk Universitet, Kongres Bygningen
        Campusvej 55, Odense
                            Indhold

Information                            2

Program                                3

Posters                                6

Abstracts, Oral                        8

Abstracts, Poster session             13

Deltagerliste                         18

Noter                                 20




                              -1-
                               Information


Mødet er arrangeret af

Dansk Selskab for Farmakologi, en paraplyorganisation for:

   •   Dansk Selskab for Farmakologi og Toksikologi
   •   Dansk Selskab for Klinisk Farmakologi
   •   Dansk Selskab for Klinisk Kemisk Farmakologi
   •   Danmarks Farmaceutiske Selskab
   •   Dansk Selskab for FarmakoEpidemiologi




Praktiske Informationer:

   •   Frokost og kaffepauser inkluderet i registreringsgebyret

   •   Middagsbilletter kan købes ved registrerings-disken

   •   Posters skal være sat op før symposiet starter

   •   Foredragsholderne bedes sørge for, at præsentationerne er klar i auditoriet
       senest 30 min før, foredraget skal afholdes




Sekretariat:

   •   Inger Marie Bro, Farmakologisk Institut, Aarhus Universitet,
       Universitetsparken 1240, 8000 Aarhus C. Tlf.: 89421726, Mobil: 20406003,
       Fax 86128804, imb@farm.au.dk,




                                       -2-
                                   Program

10.00    Registration and coffee

10.30    Introduction. Mette Rosenkilde, KU


Session 1. Pharmacodynamics
         Chairmen: Michael Mulvany, AU; Pernille B. Hansen, SDU

10.35    Ian C McGrath, Glasgow.
         Pharmacology and imaging of adrenoceptors

          Free communications:

11.20     Vladimir Matchkov, Institut for Fysiologi og Biofysik, Aarhus Universitet
          Increased reuptake masks elevated sensitivity to monoamines in periferal
          but not cerebral resistive arteries of rats depressed in response to chronic
          mild stress

11.35     Pernille Kristensen og Lene Munkholm Andersen,
          Institut for Farmakologi og Farmakoterapi, Københavns Universitet
          Combination therapy for neuropathic pain: donopezil improves gabapentin
          analgesia in nerve injured rats

11.50     Christian Bo Poulsen, Fysiologi og Farmakologi, Syddansk Universitet
          Involvement of T Type calcium channels in dilation of mouse efferent
          arterioles


12.05     Break


12.20    Kim Brøsen, SDU; Michael Mulvany, AU.
         WorldPharma Congress 2010


12.50    Lunch




                                        -3-
Session 2. Chairman: Thue Schwartz, KU; Ulf Simonsen, AU

13.50     Ian C McGrath, main editor, British Journal of Pharmacology
          Kim Brøsen, main editor, Basic and Clinical Pharmacology and Toxicology
          What is a successful manuscript in a pharmacological journal in 2010?


Session 3. Pharmacogenomics
          Chairmen: Kim Brøsen, SDU; Per Hartvig, KU

14:30     Ingolf Cascorbi, Kiel.
          Pharmacogenomics – what is the perspective?

          Free communications:

15.15     Troels K. Bergmann, Klinisk Farmakologi, Syddansk Universitet
          Impact of sequence variants in CYP2C8 on paclitaxel clearance in patients
          with ovarian cancer

15.30     Steen Hvass Ingwersen, Novo Nordisk A/S
          Quantitative pharmacology – a case for drug development

15.45     Nils Magnusson, Farmakologisk Institut, Aarhus Universitet
          Gene expression profiling of sulfonylureas in endothelial cells and vascular
          effects in diabetic ApoE null mice


Session 4. Posters

16.00     Kaffe

16.15     Guided tours

          Gruppe A: Chairmen: Ole Bjerrum, KU; Birgitte Brock, AU

          Gruppe B: Chairmen: Helle Riis Angelo; Boye Jensen, SDU




                                         -4-
Session 5. Drugs for obesity
           Chairman: Jørgen Rungby, AU; Jens Kampmann, København

17.00      Kristina Dunder, Uppsala
           CHMP’s considerations leading to rejection of Acomplia

           Free communications:

17.25      Anne Iversen, Institut for Farmakologi og Farmakoterapi, Københavns
           Universitet
           The involvement of KATP channels in neurotransmitter release

17.40      Thomas Dalsgaard, Farmakologisk Institut, Aarhus Universitet
           Novel openers of small conductance calcium-activatee potassiun channels
           enhance endothelium-dependent vasodilatation in porcine retinal arterioles


17.55      Bjørn Richelsen, Århus
           Novel drug targets for treatment of obesity

18.20      Awards for
           1) best poster and
           2) best free communication

18.30      Welcoming drink

19.00-21.00 Dinners at Restaurant EUREST
            Dinner speech Jens S. Schou




                                          -5-
                                         Posters

Poster Group A
Chairmen: Ole Bjerrum (KU); Birgitte Brock (AU)

A1
ENDOTHELIN RECEPTOR ACTIVATION REVERSES HYPOXIC VASODILATATION IN
PORCINE LARGE CORONARY ARTERIES
E.R. Nielsen, MS 1), E. Stankevicius MD 1), U. Simonsen MD, Ph.D. 1), O. Fröbert MD, Ph.D.1) 2)
1) Department of Pharmacology, University of Aarhus, Denmark
2) Department of Cardiology, Örebro University Hospital, Sweden

A2
PROSTASIN PROMOTES DEVELOPMENT OF HIGH-RESISTANCE RENAL COLLECTING
DUCT EPITHELIUM
M. Steensgaard, P. Svenningsen, A.R. Tinning, T.D. Nielsen, F. Jørgensen, G. Kjærsgaard, K.
Madsen & B.L. Jensen.
Dept. Physiolgy & Pharmacoloy, IMB, University of Southern Denmark.

A3
PULMONARY PRESSURE REDUCTION ATTENUATES EXPRESSION OF PROTEINS
IDENTIFEID BY LUNG PROTEOMIC PROFILING IN PULMONARY HYPERTENSIVE RATS
Y. Eskildsen-Helmond1, L. Østergaard1, B. Honoré2, L. Bech Thorsen1, J. Baandrup1, B.
Elmedal Laursen1, H. Vorum2, M.J. Mulvany1, U. Simonsen1
1
 Department of Pharmacology, 2Institute of Medical Biochemistry, University of Aarhus, 8000
Aarhus, Denmark

A4
NEUROPATHIC PAIN: SORTILIN IS INVOLVED IN THE DOWN-REGULATION OF KCC2
S. Neustrup, P. Møllgaard, C.V. Bjerregaard*, A. Nykjær* and O.J. Bjerrum
Dept. Pharmacology & Pharmacotherapy University of Copenhagen, 2100 Copenhagen,
*Dept. Medical Biochemistry, University of Aarhus, Ole Worms Allé, 8000 Århus C, Denmark.

A5
VASOACTIVE EFFECTS OF CYSTAMINE
M.E. Pedersen, A. Eftekhari and M.J. Mulvany
Department of Pharmacology, University of Aarhus, Universitetsparken bygn. 1240, 8000
Aarhus C, Denmark




                                               -6-
Poster Group B
Chairmen: Helle Riis Angelo; Boye Jensen (SDU)

B1
COMMUNITY PHARMACY DRIVEN PHARMACOVIGILANCE
Søren Troels Christensen & Ole Jannik Bjerrum
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences,
University of Copenhagen, 2 Universitetsparken, DK-2100, Denmark

B2
UPREGULATED EXPRESSION OF SKCa AND BKCa IN PULMONARY ARTERIES FROM
CHRONIC HYPOXIC RATS
Christel Krøigaard1, Thomas Dalsgaard1, Søren-Peter Olesen2, and Ulf Simonsen1
1
 Department of Pharmacology, Aarhus University, Denmark
2
 Department of Biomedical Sciences, University of Copenhagen, Denmark

B3
THE NOVEL KCa3.1 OPENERS SKA-20 AND SKA-31 - BUT NOT THE SEH-INHIBITOR
TAUCB - IMPROVE ENDOTHELIAL VASODILATOR RESPONSES IN MURINE CAROTID
ARTERY.
Ralf Köhler, Anna-Lena Hasenau
Dept. Physiology and Pharmacology, IMB, SDU, Odense, DK

B4
QUANTITATIVE PHARMACOLOGY- PHARMACOMETRICS. VISION FOR AN EDUCATION
PROGRAM IN DENMARK
P. Hartvig Honoré1, O.J. Bjerrum1, S.H. Ingwersen2, P. Thygeson2, K. Kristensen3, F. Larsen4
Department of Pharmacology and Pharmacotherapy1, FARMA, Copenhagen University, Novo
Nordisk A/S2, AstraZeneca3, Sweden, H. Lundbeck A/S4

B5
LITHIUM IMPAIRS KIDNEY DEVELOPMENT AND INHIBITS GLYCOGEN SYNTHASE
KINASE-3β
G. Kjaersgaard, K. Madsen, N. Marcussen, S. Christensen, B.L. Jensen
Dept. of Physiology and Pharmacology, JB Winsløwsvej 21, 3. 5000 Odense C




                                            -7-
                                      Abstracts
ORAL 1
SUCCESSIVE KNOCKOUT STRATEGY REVEALS SYNERGY BETWEEN ALPHA-1-
ADRENOCEPTOR SUBTYPES AND P2X RECEPTORS IN NERVE INDUCED VASCULAR
RESPONSES
John C.McGrath1, Paul C. Simpson2 , Craig J. Daly and Laura Methven1.1Integrative and
Systems Biology, University of Glasgow, Glasgow, G12 8QQ, UK; 2Department of Medicine,
University of California, San Francisco, CA, USA.
All 3 alpha-1-adrenoceptor (AR) subtypes could contribute to vasoconstrictor responses to
sympathetic nerve stimulation of resistance arteries and therefore contribute to autonomic
regulation of blood pressure. However, analysis is beset by poor selectivity of agonist and
antagonist drugs and the sheer complexity of dissecting out the individual contributions from
these receptors plus other adrenoceptors and receptors to potential co-transmitters. We have
used confocal microscopy (with fluorescent ligands) to localise and identify alpha-1-AR present
in the various cell types of small mesenteric arteries, identifying subtypes using double and
triple knockouts of the alpha-1-AR. We then analysed responses to agonsist and to electrical
field stimulation in wire-myograph-mounted arteries. The results show that alpha-1A-AR and
alpha-1D-AR act synergistically, particularly at low concentrations of agonists and low frequency
nerve stimulation, so that antagonists of either receptor produced a powerful blockade. After
elimination of all 3 alpha-1-AR there remained a P2X-mediated response blocked by alpha, beta,
methylene ATP; antagonist analysis of the double knockouts revealed synergism between P2X
and alpha-1A-AR but not between P2X and alpha-1D-AR. This reveals a pattern of powerful
synergism between purinergic and adrenergic responses with a degree of adrenoceptor
selectivity, pointing to signalling interactions. Supported by British Heart Foundation
(PG/05/140/20094 and FS/04/035).

ORAL 3
CHMP’S CONSIDERATIONS LEADING TO THE WITHDRAWAL OF ACOMPLIA.
Kristina Dunder, MD, PhD, clinical assessor, Medical Products Agency, Uppsala, Sweden
   Acomplia (Rimonabant) is a selective cannabinoid-1 receptor antagonist with central and
peripheral effects with the ability to modulate food intake and reduce body weight. Acomplia
was approved in June 2006 as a weight reducing agent. The studies included in the approval-
file showed that 50 and 25-30% of the patients treated with Acomplia reduced their weight with
5 and 10%, respectively. The risk of psychiatric disorders was almost doubled compared to
patients given placebo. However, warnings and contraindications were included in the product
information with the purpose to minimize risks.
   After approval, periodic safety updates indicated an increased reporting rate of depression
and aggressivity. The product information was strengthened and information letters were
distributed to prescribers. Results from a new study could not show that Acomplia had a
beneficial effect on the progression of atherosclerosis, which is the ultimate goal of the
treatment.
   The CHMP decided to re-evaluate the benefit/risk balance for Acomplia. The company
submitted all available study results and post marketing data which were assessed by CHMP
members and external scientific experts. During this assessment it was found that the warnings
in the product information had not had the expected effect and that the mean duration of
treatment was no more than 3 months. Furthermore, 5 new suicides were reported in ongoing
studies. After assessing all data, the conclusion of the CHMP was that the benefits of treatment
with Acomplia were more limited and the risks higher compared to what was foreseen at the
time of approval. The benefit/risk balance was considered as negative and a suspension of
Acomplia was recommended.




                                              -8-
                           Free communications
Abstract 1
INCREASED REUPTAKE MASKS ELEVATED SENSITIVITY TO MONOAMINES IN
PERIFERAL BUT NOT CEREBRAL RESISTIVE ARTERIES OF RATS DEPRESSED IN
RESPONSE TO CHRONIC MILD STRESS
V. Matchkov, E. Bouzinova, T. Brøgger, N. Møller Nielsen, K. Henningsen, O. Wiborg, C.
Aalkjær
  Depression and cardiovascular disease are known to occur simultaneously but the reason for
this is unclear. In chronic mild stress (CMS) model of depression only some rats develop
depression-like symptoms, while others are stress-resistant (resilient). CMS rats are shown to
havea reduced cardiac output and unchanged blood pressure suggesting increase in total
peripheral resistance (TPR).
  To study the reason for elevated TPR in CMS rats after 8 weeks exposure to variable and
unpredictable stress we have assessed in vitro isometric force development in the middle
cerebral (CA), femoral (FA) artery and mesenteric small arteries (MSA).
  Passive inner diameters were not different between the groups. MSA from all three groups
developed similar maximal tension to noradrenaline (NA). MSA were also similarly sensitive to
NA under control conditions but cocaine unmasked elevated NA sensitivity of MSA from
depressed rats consistent with elevated neuronal reuptake of NA. FA from depressed rats also
demonstrated increased sensitivity to NA which had been masked by elevated NA reuptake. In
addition, the maximal tension to NA of FA from depressed rats was higher in comparison to the
control and resilient groups. CA from depressed rats were more sensitive to 5-HT in comparison
to the resilient and non-stressed groups. This difference was not affected by cocaine. The
observed changes in the arterial responses to monoamine correlated with changes in
corticosterone which transiently increased to stress and the transient lasted longer in the
depressed rats.
  Thus, our results indicate that depression is associated with changes in the contractility and
agonist sensitivity of resistance arteries. These changes might be important for the
cardiovascular events associated with depression.

Abstract 2
COMBINATION THERAPY FOR NEUROPATHIC PAIN: DONEPEZIL IMPROVES
GABAPENTIN ANALGESIA IN NERVE INJURED RATS
P.Kristensen, L.M. Andersen, A. Folkesson, P.H. Honoré, O.J. Bjerrum
Department of Pharmacology and Pharmacotherapy, University of Copenhagen,
Universitetsparken 2, 2100 København Ø, Denmark.
   Neuropathic pain is a burden for the patients and society. No single treatment gives sufficient
pain relief in all patients. The alfa-2-delta-receptorantagonist, gabapentin is currently the first
choice drug for treatment of neuropathic pain and it activates the descending noradrenergic-
cholinergic pathway. Donepezil, a selective, non-competitive and reversible inhibitor of
acetylcholinesterase, approved for symptomatic treatment of Alzheimer’s disease, and the
antidepressant venlafaxine (a serotonin, noradrenaline reuptake inhibitor) both act on this
pathway and may be attractive agents in combination with gabapentin. Previous single dosing
studies of these drug combinations, performed in a rat model of neuropathic pain in-house,
have shown such encouraging results that a clinical study was planned. To further mimic the
clinical situation, a sub-chronic dosing study was conducted.
   The Spared Nerve Injury (SNI) model was used to induce hypersensitivity of the rat’s
hindpaw. Rats received gabapentin once daily in 10 days followed by 10 days of co-
administration with donepezil or venlafaxine, respectively. Control groups received either a fixed
dose of gabapentin or vehicle in both periods. Mechanical hypersensitivity was determined with
von Frey filaments.
   Gabapentin dose-dependently reversed mechanical hypersensitivity in the SNI model. Co-
administration with donepezil significantly reduced mechanical hypersensitivity in comparison to
gabapentin administered alone, whereas co-administration with venlafaxine was in borderline.
                                               -9-
Thus, this sub-chronic dosing study confirms the previous findings from the single dosing
studies, and supports the rationale for a clinical study.

Abstract 3
INVOLVEMENT OF T TYPE CALCIUM CHANNELS IN DILATION OF MOUSE EFFERENT
ARTERIOLES
C.B. Poulsen1, R. H. Al-Mashhadi1, L. Cribbs2, O. Skøtt1, P. B. Hansen1.
1
 Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense, Denmark.
2
 Cardiovascular Institute, Loyola University Medical Center, Maywood, Il, USA
   Objektive: Voltage gated calcium channels (Cav) are involved in the excitation-contraction
mechanism of renal resistance vessels and play an essential role in regulation of renal blood
flow and glomerular filtration rate. T-type Cav (Cav3.2) has recently been shown to be involved
in relaxation of coronary arteries. We investigated the involvement of T-type channels in
dilatation of efferent arterioles.
  Methods: Microdissected perfused mouse efferent arterioles, PCR on microdissected vessels
and immunohistochemistry.
  Results: In efferent arterioles a transient vasoconstriction was observed in response to
depolarization with potassium (7.9 µm ± 0.3 to 0.1 µm ± 0.1) lasting for 16.2 ± 7.0 seconds. A T
type antagonist, nickel10-6M blocking Cav 3.2, changed the postassium elicited constriction to a
sustained response lasting 48.2 ± 1.1 seconds. Inhibition of eNOS by L-NAME (5·10-5M ) or
deletion of eNOS had similar effect on the vasoconstrictor response. PCR analysis showed
expression of T-type subtypes Cav 3.1 and Cav 3.2 in microdissected efferent arterioles and
immunohistochemistry revealed Cav 3.1 in mouse efferent arterioles. Furthermore, Cav 3.2
protein was observed in endothelia and vascular smooth muscle cells in rat renal vasculature.
Whether Cav3.2 was involved in dilator responses in general was tested using acetylcholine.
U46619 (10-6M) resulted in a luminal diameter of 1.4 ± 1.4 µm and acetylcholine (10-6M)
increased the luminal diameter to 7.6 ± 0.2µm. L-NAME abolished the acetylcholine induced
dilation whereas Cav 3.2inhibition by nickel had no effect.
   Conclusion: T-type channels Cav3.2 are involved in the spontaneous dilatation occurring in
renal efferent arterioles after the initial constriction that follows a depolarization.

Abstract 4
IMPACT OF SEQUENCE VARIANTS IN CYP2C8 ON PACLITAXEL CLEARANCE IN
PATIENTS WITH OVARIAN CANCER
T.K.Bergmann(1) W.Vach(2) H.Green(3) M.O.Karlsson(4) L.Friberg(4) F.Nielsen(1)
R.S.Pedersen(1) M.R.Mirza(5) C.Brasch-Andersen(1) K.Brøsen(1)
1) Clinical Pharmacology, University of Southern Denmark; 2) Institute of Language and
Communication, University of Southern Denmark; 3) Clinical Pharmacology, Linkoping
University, Sweden; 4) Division of Pharmacokinetics and Drug Therapy, Uppsala University,
Sweden; 5) Dept of oncology, Odense University Hospital, Denmark.
  The primary purpose of this study was to evaluate the impact of CYP2C8*3 and three genetic
ABCB1 variants on the elimination of paclitaxel.
  We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin.
Using sparse sampling and non linear mixed effects modeling, the individual clearance of
unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL.
  The geometric mean of clearance was 385 l/h (range 176-726 l/h). Carriers of CYP2C8*3 had
11% lower clearance than non carriers, P=0.03.
  This has not been demonstrated before in similar studies; the explanation is probably the
advantage of using both unbound paclitaxel clearance and a population of patients of same
gender.
  No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T.
Secondarily other candidate SNPs were explored with possible associations found for
CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).
  This abstract was also presented at ECCO, Berlin sept 2009.


                                             - 10 -
Abstract 5
QUANTITATIVE PHARMACOLOGY – A CASE FOR DRUG DEVELOPMENT
S.H. Ingwersen
Dept. of Biomodelling, Novo Nordisk A/S, DK2860 Søborg, Denmark
   The introduction of Pharmacokinetic/Pharmacodynamic (PK/PD) modelling by means of a
population approach has resulted in a new paradigm in Quantitative Pharmacology. This
reseach area is now a well-established scientific discipline – also known as Pharmacometrics –
and during recent years, the pharmaceutical industry has accelerated its use for decision
making in drug discovery and development. This is due to some highly attractive properties of
pharmacometric models.
   PK/PD models describe the variation in time of drug concentration in blood as well as the
pharmacological response following drug dosing. When implemented as population PK/PD
models, they can be used to analyse the pharmacokinetic and pharmacodynamic properties of
drugs in populations of subjects. This is accomplished by including the variability between
subjects and within subjects within the models.
   When based on relevant data, a population PK/PD model may be used to simulate the most
likely outcome of a subsequent clinical trial. Simulations are useful for obtaining the most
optimal design of a trial with respect to patient characteristics, dose selection, dosing regimen,
powering, blood sampling etc. Moreover, if a model is based on data from a population with a
range of demographic characteristics, it may be used to conduct a covariate analysis of the
pharmacokinetics or pharmacodynamics of a drug. Such covariate analyses are often included
in new drug applications.
   General principles as well as case stories from the use of PK/PD modelling and simulation for
decision making in drug development will be presented.

Abstract 6
GENE EXPRESSION PROFILING OF SULFONYLUREAS IN ENDOTHELIAL CELLS AND
VASCULAR EFFECTS IN DIABETIC ApoE NULL MICE
N.E. Magnusson1,2, M.E. Cooper2, J. Rungby1.
1
 Pharmacology, University of Aarhus, DK,
2
 Baker IDI Heart and Diabetes Institute, Melbourne, AUS.
  Aims: To evaluate the potential different vascular effects of sulfonylureas (SUs) we assessed
the impact of two SUs on endothelial cell gene expression and compared the effects on plaque
development in a model of diabetes associated atherosclerosis.
  Methods: HUVEC cells were exposed to gliclazide or glibenclamide for 24 hours (n=3). Gene
expression was analyzed using GeneChip arrays. Streptozotocin diabetic Apolipoprotein E
(ApoE) knockout (KO) mice were treated with either glibenclamide or gliclazide for 20 weeks.
Plaque areas were quantitated by the en face method.
  Results: Glibenclamide increased the expression of iNOS whereas gliclazide reduced the
expression (p<0.005). Comparison of upregulated genes showed an increased significance for
gliclazide over glibenclamide of nitric oxide signaling in the cardiovascular system as well as
pathways linked to PDE5, the target of sildenafil. Plaque areas in diabetic ApoE deficient mice
treated with glibenclamide showed a significant increase in total plaque area compared to
untreated and gliclazide treated mice (17.5 ± 2.7%, p<0.02 vs. other groups). No differences
were observed between gliclazide and untreated diabetic ApoE KO mice.
  Conclusions: The differences in gene expression between drugs were more pronounced than
the similarities suggesting a differential profile among SUs in endothelial cells. These
differences may be relevant to the disparate vascular effects seen in vivo in preclinical models
of diabetic atherosclerosis with glibenclamide and gliclazide.




                                              - 11 -
Abstract 7
THE INVOLVEMENT OF KATP CHANNELS IN NEUROTRANSMITTER RELEASE
Anne Iversen1, Kenneth B Ploug2, Inger Jansen-Olesen2, Trine M Lund1
1: Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences,
University of Copenhagen, Denmark. ai@farma.ku.dk.
2: Department of Neurology, Glostrup Hospital, Denmark.
  It is well known that both starvation and a very fat diet have an anticonvolsive effect on
patients with epilepsy. In both cases, the patients obtain a high blood level of ketone bodies,
which are used by the brain as energy substrates when glucose is restricted. Our hypothesis is
that the ketone body, β-hydroxybutyrate, inhibits glycolysis, leading to a lower ATP level near
the plasmamembrane. The lower ATP level leads to more open KATP channels and therefore a
hyperpolarisation of the neurons, causing decreased neurotransmitter release.
  The purposes of this project are first of all to characterize KATP channels on a molecular level
in primary neuron cultures and furthermore to determine whether these channels are involved in
neurotransmitter release.
  The molecular characterization of the KATP channels is carried out using qPCR and Western
blot analysis to determine mRNA and protein levels of different KATP channel subunits. The
subunit composition of these channels has great importance to the physiological function.
The involvement of KATP channels in neurotransmitter release from cultured cortical neurons is
studied using 3H-GABA in the presence of KATP channel openers and blockers.

Abstract 8
NOVEL OPENERS OF SMALL CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM
CHANNELS ENHANCE ENDOTHELIUM-DEPENDENT VASODILATATION IN PORCINE
RETINAL ARTERIOLES
T Dalsgaard1, C Kroigaard1, M Misfeldt, T Bek, U Simonsen1
1
 Department of Pharmacology, Aarhus University, Denmark
  Background: The present study investigated whether the selective opener of small (SKCa)
and intermediate (IKCa) conductance calcium-activated potassium channels, NS309 (6,7-
dichloro-1H-indole-2,3-dione 3-oxime), or the selective opener of SKCa2 and SKCa3 channels,
CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine), enhanced
endothelium-dependent          vasodilatation       in     porcine       retinal        arterioles.
  Methods: Localisation of SKCa3 and IKCa protein was examined by immunolabelling.
Endothelial cell calcium was measured by fluorescence imaging with oregon green. For
functional studies, arterioles were mounted in microvascular myographs for isometric tension
recordings and concentration-response experiments for bradykinin, NS309, and CyPPA, were
constructed.
  Results: SKCa3 and IKCa protein was localised in the endothelium. Bradykinin, but not
NS309, increased endothelial cell calcium. In contrast to a nitric oxide (NO) donor, sodium
nitroprusside, pre-incubation with NS309 or CyPPA enhanced bradykinin relaxation. This
enhanced relaxation was abolished by blocking SKCa channels with apamin. In the presence of
NS309 or CyPPA, inhibition of NO synthase with asymmetric dimethylarginine and/or
cyclooxygenase with indomethacin markedly reduced bradykinin relaxation. Bradykinin
relaxation was completely abolished by inhibition of NO synthase and cyclooxygenase together
with a NO scavenger, oxyhaemoglobin.
  Conclusions and implications: In porcine retinal arterioles, SKCa3 and IKCa protein is
localized to the vascular endothelium. Bradykinin increases endothelial cell calcium followed by
opening of SKCa and IKCa channels. Without altering endothelial cell calcium, NS309
enhances bradykinin relaxation by activating SKCa channels, which is mainly mediated by NO.
These results implicate that opening SKCa channels improves endothelium-dependent
relaxation and make them a potential target for treatments aimed at restoring retinal blood flow.




                                              - 12 -
                                  Poster Session
Poster A1
ENDOTHELIN RECEPTOR ACTIVATION REVERSES HYPOXIC VASODILATATION IN
PORCINE LARGE CORONARY ARTERIES
E.R. Nielsen, MS 1), E. Stankevicius MD 1), U. Simonsen MD, Ph.D. 1), O. Fröbert MD, Ph.D.1) 2)
1) Department of Pharmacology, University of Aarhus, Denmark
2) Department of Cardiology, Örebro University Hospital, Sweden
  The present study investigated the role of endothelin-1 (ET-1), the nitric oxide (NO) pathway, and
radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Porcine coronary
artery segments were mounted for functional studies in wire and pressure myographs. We
measured tissue concentrations of ET-1 by ELISA assay and asymmetric dimethylarginine (ADMA)
by HPLC. NO concentrations were measured with a microsensor.
  In prostaglandin F2α-contracted segments with endothelium, gradual lowering of oxygen tension
from 95 to 0% O2 resulted in vasodilation. The response to O2 lowering was rightward shifted in
segments without endothelium, but not at 0% O2. The endothelin receptor antagonist SB217242
markedly increased hypoxic dilation and exogenous ET-1 reversed hypoxic vasodilation in
segments with and without endothelium. The free tissue ET-1 concentration in the arterial wall was
reduced by 20% in 0% O2 versus 21% O2. Without affecting basal NO, hypoxia increased NO
concentration in PGF2α-contracted arteries, and a NO synthase inhibitor LNNA, reduced hypoxic
vasodilation. ADMA concentrations were unchanged by hypoxia. The superoxide scavenger tiron
and the putative NADPH oxidase inhibitor apocynin had no effect on 0% O2 vasodilatation although
a leftward shift in concentration-response curves for O2 was noticed at 10%-20% O2. Endothelin
receptor activation reverses while endothelin receptor antagonism markedly enhances hypoxic
vasodilation in coronary artery segments with and without endothelium. Endothelium-derived NO
may counteract the effects of ET-1 during hypoxia.

Poster A2
PROSTASIN PROMOTES DEVELOPMENT OF HIGH-RESISTANCE RENAL COLLECTING
DUCT EPITHELIUM
Steensgaard M, Svenningsen P, Tinning AR, Nielsen TD, Jørgensen F, Kjærsgaard G, Madsen
K & Jensen BL.
Dept. Physiolgy & Pharmacoloy, IMB, University of Southern Denmark.
  Prostasin (CAP1) is a GPI-anchored serine protease necessary for acquisition of barrier
function in epidermis. We hypothesized that prostasin is essential for postnatal development of
high resistance renal collecting duct epithelium governed by glucocorticoid. In rat kidney cortex
and medulla, prostasin mRNA level increased significantly between birth and weaning (day 21),
independent of adrenal steroids, and was detected in collecting ducts. Mouse cortical collecting
duct cells (M-1) were seeded at 4×105 cells/ml and developed increased transepithelial
resistance (TER) and –voltage (TEV) and a significant increase in prostasin mRNA and protein
level (~2 times) after 1 week. The serine protease inhibitor aprotinin inhibited development of
TER and TEV and led to aberrant localization of E-cadherin, when added to the apical but not
the basolateral side of M-1 monolayers. This effect on TEV and TER was mimicked by the
prostasin inhibitor nafamostat. Apical addition of phosphoinositide-specific phospholipase C
which cleaves GPI anchors released prostasin to the medium and impaired development of
TER. Disruption of lipid rafts by methyl-β-cyclodextrin attenuated development of TER and TEV.
Omission of the synthetic glucocorticoid dexamethasone impaired development of TER and
TEV, but had no effect on prostasin protein abundance and did not affect E-cadherin
redistribution. Conclusion: apical, GPI-anchored, lipid raft-associated serine protease activity,
compatible with prostasin, is necessary for establishment of tight collecting duct epithelium
independently of glucocorticoid.




                                               - 13 -
Poster A3
PULMONARY PRESSURE REDUCTION ATTENUATES EXPRESSION OF PROTEINS
IDENTIFEID BY LUNG PROTEOMIC PROFILING IN PULMONARY HYPERTENSIVE RATS
Y. Eskildsen-Helmond1, L. Østergaard1, B. Honoré2, L. Bech Thorsen1, J. Baandrup1, B.
Elmedal Laursen1, H. Vorum2, M.J. Mulvany1, U. Simonsen1
1
 Department of Pharmacology, 2Institute of Medical Biochemistry, University of Aarhus, 8000
Aarhus, Denmark
  In the present study protein regulation in lungs of chronic hypoxic rats was analysed in order
to identify novel signalling pathways, finding possible new targets for treatment of pulmonary
hypertension.
  Proteomics was performed and proteins from lung homogenates from five hypoxic rats were
compared to five normoxic rats. Furthermore protein expression and correlation to alterations in
vascular muscularization was investigated in lungs from hypoxic rats receiving treatment with
either an activator of soluble guanylyl cyclase, BAY 412272, or an inhibitor of
phosphodiesterase type 5, sildenafil.
  The proteomic study revealed amongst others upregulation of guanine nucleotide-binding
protein β (Gbβ), glutathione S transferase omega 1, cathepsin D (CatD), Annexin A4 and F-
actin capping protein CapZ (CapZα) in lungs from chronic hypoxic rats with pulmonary
hypertension. Immunohistochemistry showed that many of these proteins were expressed in the
pulmonary vascular wall (e.g. CapZα, CatD, and annexin A4) and immunoblotting showed these
proteins correlated to alterations in muscularization. Both treatments inhibited hypoxia-induced
increase in right ventricular systolic pressure and pulmonary arterial muscularization and
prevented most of the protein regulations observed after hypoxia.
  These findings suggest that pulmonary pressure is an important factor for initiating signaling
pathways leading to protein expression and muscularization in the pulmonary vasculature.

Poster A4
NEUROPATHIC PAIN: SORTILIN IS INVOLVED IN THE DOWN-REGULATION OF KCC2
Neustrup S., Møllgaard P., Bjerregaard C.V*., Nykjær A* and Bjerrum O.J
Dept. Pharmacology & Pharmacotherapy University of Copenhagen, 2100 Copenhagen,
*Dept. Medical Biochemistry, University of Aarhus, Ole Worms Allé, 8000 Århus C, Denmark.
  The chronic condition neuropathic pain represents a major clinical burden. The pathogenesis
is complex and not fully elucidated. Previous studies establish that nerve injury causes
increased release of brain-derived neurotrophic factor (BDNF) in the spinal dorsal horn leading
to down-regulation of K+/Cl--co-transporter 2 (KCC2) and hence to development of neuropathic
pain. Based on the departments’ original observation that the neuronal protein sortilin may be
an important component in the pathogenesis of neuropathic pain we put forward the hypothesis:
“Sortilin is involved in the down-regulation of KCC2 leading to neuropathic pain”.
  A comparative study of the behavioural and biochemical changes after nerve injury in sortilin
knockout (KO) and wild-type C57Bl/6 mice was conducted. Symptoms correlating the clinical
manifestations seen in neuropathic pain in humans were induced by the Spinal Nerve Ligation
(SNL) model. von Frey (mechanical allodynia) and Hargreaves (thermal hyperalgesia) test
showed significant signs of hypersensitivity in WT mice in contrast to KO mice. Immunoblotting
of L1-L3 spinal segments showed that after SNL surgery KCC2 was down-regulated in WT but
not in KO mice. The hypothesis was confirmed by coincided results demonstrating that SNL KO
mice did not develop symptoms of neuropathic pain and had a stable level of KCC2 after SNL,
as opposed to WT mice. In conclusion, our studies establish that sortilin constitutes a key
element in the pathophysiology of neuropathic pain.




                                             - 14 -
Poster A5
VASOACTIVE EFFECTS OF CYSTAMINE
M.E. Pedersen, A. Eftekhari and M.J. Mulvany
Department of Pharmacology, University of Aarhus, Universitetsparken bygn. 1240, 8000
Aarhus C, Denmark
   Essential hypertension (EH) is associated with inward eutrophic remodelling of resistance
arteries. Alterations are observed in small artery structure with a narrowing of the lumen
diameter and increase in media:lumen ratio. The ubiquitous enzyme tissue-Transglutaminase
(tTG) has been shown to play a part in this process. Cystamine (CYS), an organic disulfide and
competitive inhibitor of tTG, has been demonstrated to inhibit small artery remodelling in rats. In
this study we investigate the vasoactive effects of cystamine in rats. Small mesenteric arteries
were mounted in wiremyographs for simultaneous measurements of [Ca2+]i and force. Dose
response relationships were performed with or without presence of CYS. CYS reduced the
response to phenylephrine (Phe), 5-HT and U46619 in a concentration dependent manner. No
significant effect was observed on K+PSS dose response curves with CYS in concentrations up
to 10-4M. CYS 10-3M caused complete inhibition of all agonist induced responses. In Phe
precontracted vessels CYS 10-4M caused a transient fall (11 ± 1.8 min) in [Ca2+]i and active
tension, followed by a rise in Ca2+-influx and tension. In vessels precontracted with KPSS CYS
10-4M caused a significant reduction in active tension without altering [Ca2+]i indicating a Ca2+-
desensitization effect of cystamine.
   We conclude that the vasoactive effects of CYS involve dose-dependent inhibition of agonist
induced contractions, through a specific mechanism rather than non-specific blocking of Ca2+-
channels. We speculate that this may involve Ca2+-desensitization. The possible role of these
findings in remodelling remains to be established.

Poster B1
COMMUNITY PHARMACY DRIVEN PHARMACOVIGILANCE
Søren Troels Christensen & Ole Jannik Bjerrum
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences,
University of Copenhagen, 2 Universitetsparken, DK-2100, Denmark
  Post-marketing safety studies of adverse drug reactions (ADRs) form an important part of
pharmacovigilance. Countries having formal pharmacovigilance systems rely on voluntary ADR
reporting from health professionals e.g. through spontaneous report systems. However, SRS
suffers from underreporting which hampers fast detecting of ADRs for instance in relation to
newly launched medicines. Pharmacist are in a unique position for detection of medicine users
experienced ADRs.
  Objective: To answer the question if proactive ADR detection and reporting is feasible through
direct medicine user interaction in the community pharmacy counter setting?
  Method: Ibuprofen was chosen as the drug of study. Pharmacy students undertaking
internship in a community pharmacy were chosen as proxies for community pharmacists. 13
students participated as data collectors asking recurrent medicine users about experienced
ADRs. Reported ADRs were collected and analysed.
  Results: 128 Ibuprofen users participated of whom 33 reported 45 ADRs likely linked to
Ibuprofen usage. The reported ADRs followed nearly earlier reported patterns of distribution
which gastric pain most commonly reported followed by heartburn, nausea, diarrhoea and
constipation.
  Conclusions: Through adequate training community pharmacists are capable of detecting and
reporting ADRs through direct medicine user questioning. In the community pharmacy setting
this could take place upon drug dispensing of recurrent medicine users as part of intensive
monitoring of newly launched medicines or in the relation to formal cohort studies.




                                              - 15 -
Poster B2
UPREGULATED EXPRESSION OF SKCa AND BKCa IN PULMONARY ARTERIES FROM
CHRONIC HYPOXIC RATS
Christel Krøigaard1, Thomas Dalsgaard1, Søren-Peter Olesen2, and Ulf Simonsen1
1
 Department of Pharmacology, Aarhus University, Denmark
2
 Department of Biomedical Sciences, University of Copenhagen, Denmark
  Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormal
constriction of pulmonary arteries, proliferative vasculopathies, and finally organ failure. Present
treatments do not sufficiently prevent PAH and therefore there is interest in new
pharmacological approaches. We hypothesized that an increase in calcium-activated potassium
(KCa) channel expression could be observed as a compensatory mechanism to counteract PAH.
For this purpose we investigated the expression of small (SK), intermediate (IK) and large (BK)
conductance KCa channels in lungs of normotensive/normoxic rats (n=6) and chronic hypobaric
hypoxic rats (n=7) that develop PAH and right ventricular hypertrophy. Bronchioles and
intrapulmonary arteries were isolated and the expression of KCa channels investigated by QPCR,
immunohistochemistry and Western blotting. IK and SK3 immunoreaction was found in the
arterial endothelium and bronchial epithelium. At mRNA level, KCa channels were expressed in
the following order in rat bronchioles and arteries: BKβ1>>SK1>IK=BKα>SK3>>SK2. In arteries,
BKβ1 mRNA and BKα mRNA and protein expression was upregulated by hypoxia. IK mRNA
expression was higher in arteries than bronchioles and unaltered in tissue from chronic hypoxic
rats. mRNA for SK1, SK2 and SK3 was unaltered by hypoxia, whereas SK3 protein was
upregulated in arteries exposed to hypoxia. In conclusion, in the chronic hypoxic rat both SK3,
BK β1 and BKα was upregulated in pulmonary arteries. In recent studies we found that KCa
openers dilate pulmonary arteries and with the present results this suggests that drugs opening
KCa channels may be beneficial for the treatment of PAH.

Poster B3
THE NOVEL KCA3.1 OPENERS SKA-20 AND SKA-31 - BUT NOT THE SEH-INHIBITOR
TAUCB - IMPROVE ENDOTHELIAL VASODILATOR RESPONSES IN MURINE CAROTID
ARTERY.
Ralf Köhler, Anna-Lena Hasenau
Dept. Physiology and Pharmacology, IMB, SDU, Odense, DK
  Endothelial KCa3.1 and KCa2.3 channels and CYP450-generated epoxy-eicosatrienoic acids
(EETS) have been proposed to be important mediators of endothelium-derived hyperpolarizing
factor(EDHF)-mediated dilator responses. In the present study using electrophysiology and
pressure myography, we tested the hypothesis whether pharmacological opening of KCa3.1
and KCa2.3 and inhibition of EET degradation by the soluble epoxide hydrolase (sEH) improve
endothelial dilator responses.
  We found that SKA-20 and SKA-31 (1) potentiated KCa3.1 and KCa2.3 with EC50 values of
142 nM (SKA-20) and 225 (SKA-31) for KCa3.1 and with EC50 values of 1.5 uM (SKA-20) and
1.6 (SKA-31) for KCa2.3. SKA-20 and SKA-31 dose-dependently enhanced ACh-induced
EDHF-dilations in murine carotid arteries. This effect was not seen in KCa3.1 deficient mice.
Selective inhibition of sEH by tAUCB (2) had no effect on ACh-induced EDHF-dilations in wt or
KCa3.1-deficient mice.
  In conclusion, endothelial EDHF-dilator responses in mice can be improved by
pharmacological potentiation of KCa3.1 and (KCa2.3) channels but not by increasing EET
availability via inhibition of sEH.




                                              - 16 -
Poster B4
QUANTITATIVE PHARMACOLOGY- PHARMACOMETRICS. VISION FOR AN EDUCATION
PROGRAM IN DENMARK
P Hartvig Honoré1, OJ Bjerrum1, SH Ingwersen2, P Thygeson2, K Kristensen3, F Larsen4
Department of Pharmacology and Pharmacotherapy1, FARMA, Copenhagen university, Novo
Nordisk A/S2, AstraZeneca3, Sweden, H. Lundbeck A/S4
  Pharmacometrics describe the time course of drug response, identifies individual factors, co-
variates which predicts the difference in response and the design of clinical trials to elucidate
drug properties. It is based on sound knowledge of biology and pharmacology. as well as
mathematical-statistical skills. The ability to describe clinical and experimental obser-vations of
drug action and its time course must be firmly based on pato-physiological, drug mechanisms
and disposition concepts. Further basic concepts of statistics and mathematics are necessary
for the application pharmacometric methods. In essence pharmacometrics is rational scienti-fic
basis for determination of correct dose for an individual patient resting on the disciplines of
pharmacokinetics and pharmacodynamics with quantitative expression of dose-response
relations. Development of quantitative estimates from pharmacokinetics and
pharmacodynamics is of profound importance in development of drugs.
  It is of great importance that excellent and qualitative education is at hand to the benefit of the
Danish drug industry, to patients and to society. The visions are, first to create a
pharmacometric curriculum (N Holford, MO Karlsson. Clin Pharmacol Ther 2007; 82:103-5 built
in several modules to gradually increase knowledge. Second, to create an integra-ted scientific
platform for Quantitative Pharmacology by net-working with dedicated scientists at neighbour
universities and third, profiling and promotion of Quantitative Pharmacology research and
education at Farma
  The education part is in progress and the purpose of an advanced course held week 12, 2010
is: to provide participants with knowledge about population pharmacokinetics and underlying
concepts; to establish rules for the rational development of a population pharmacokinetic model;
to predict dose using a priori and posteriori methods; to handle a data set used in population
kinetic calculations and to provide practical training.

Poster B5
LITHIUM IMPAIRS KIDNEY DEVELOPMENT AND INHIBITS GLYCOGEN SYNTHASE
KINASE-3β
G.Kjaersgaard, K. Madsen, N. Marcussen, S. Christensen, B.L. Jensen
Dept. of Physiology and Pharmacology, JB Winsløwsvej 21, 3. 5000 Odense C
  Lithium (Li+) is used to treat affective disorders. Developmental kidney injury after Li+ has
been described in rat. In kidney, Li+ inhibits Glycogen Synthase Kinase-3β (GSK-3β) by
increased phosphorylation on serine9 (s9). In the present study, we hypothesised that Li+ leads
to damage of the developing kidney through inhibition of GSK-3β and subsequent epithelial to
mesenchymal transition (EMT).
  Through postnatal rat kidney development GSK-3β and pGSK-3β-s9 protein abundances in
cortex decreased significantly. In kidney medulla, only pGSK-3β-s9 decreased significantly with
development. Immunohistochemical labelling for GSK-3β and pGSK-3β-s9 showed signals
associated with the collecting duct system in human kidney and postnatal rat kidney. Li+ was
given through the chow to female Wistar rats with litters through postnatal (P) day P7-P29. At
P29, Li+-treated rat pups were polyuric and their kidneys exhibited dilated pelvis with medullary
atrophy. Stereological analysis showed reduction of total kidney volume and a volume reduction
of all kidney zones except for inner medulla. Li+-treatment increased pGSK-3β-s9 protein level
significantly in pup kidney whereas total GSK-3β expression was unaltered. Lithium treatment
did not alter the localisation of GSK-3β as determined by immunohistochemistry. In addition, Li+-
treatment increased α-SMA protein level significantly whereas E-cadherin expression was
unaltered.
  In conclusion, Li+-treatment disturbs normal development of the kidney medulla, increases
phosphorylated, inactive GSK-3β abundance in collecting duct and leads to EMT. The data are
compatible with the notion that GSK-3β activity is necessary for kidney development.
                                               - 17 -
         Deltagerliste (pr. 14. januar 2010)

Lene Munkholm Andersen                Københavns Universitet
Christian Buus Andersen               Pfizer ApS
Helle Riis Angelo
Bo Ankerstjerne                       Københavns Universitet
Helle Byg Armandi                     Bispebjerg Hospital
Ann Mosegaard Bak                     Aarhus Universitet
Birgitte Bejder                       GlaxoSmithKline Pharma A/S
Troels Bergmann                       Syddansk Universitet
Tanja Bidstrup                        Odense Universitetshospital
Bine Bjerregaard                      Lægemiddelstyrelsen
Ole Bjerrum                           Københavns Universitet
Inger Marie Bro                       Aarhus Universitet
Birgitte Brock                        Aarhus Universitet
Christina Brock                       Ålborg Sygehus
Kim Brøsen                            Syddansk Universitet
Ingolf Cascorbi                       University Hospital Schleswig-Holstein
Palle Mark Christensen                Region Syddanmark
Sten Christensen                      Københavns Universitet
Mette Marie Christensen               Syddansk Universitet
Søren Troels Christensen              Københavns Universitet
Hanne Rolighed Christensen            Bispebjerg Hospital
Mikkel Christensen                    Bispebjerg Hospital
Thomas Dalsgaard                      Aarhus Universitet
Per Damkier                           Odense Universitetshospital
Dorthe Dideriksen                     Odense Universitetshospital
Kristina Dunder                       Läkemedelsverket, Uppsala
Yvonne Eskildsen-Helmond              Aarhus Universitet
Anna Folkesson                        Københavns Universitet
Ulla Friis                            Syddansk Universitet
Anja Gouliaev                         Aarhus Universitet
Thomas Graham                         Schering-Plough A/S
Thor Buch Grønlykke                   Bispebjerg Hospital
Jesper Hallas                         Syddansk Universitet
Pernille B.L. Hansen                  Syddansk Universitet
Ulla Hedegaard                        Odense Universitetshospital
Helle Holst                           Bispebjerg Hospital
Per Hartvig Honoré                    Københavns Universitet
Henrik Horneberg                      Syddansk Universitet
Lotte Høgberg                         Bispebjerg Hospital
Camilla Haahr                         Københavns Universitet
Steen Hvass Ingwersen                 Novo Nordisk A/S
Anne Iversen                          Københavns Universitet
Boye Jensen                           Syddansk Universitet
Torben Johansen                       Syddansk Universitet
Jeanette Hoff Juul                    Norpharma A/S
Jens Peter Kampmann                   Bispebjerg Hospital
Lene Juel Kjeldsen                    SAFE, Amgros

                             - 18 -
Charlotte Kjærgaard                  Bispebjerg Hospital
Gitte Kjærsgaard                     Syddansk Universitet
Ralf Koehler                         Syddansk Universitet
Pernille Kristensen                  Københavns Universitet
Kim Kristensen                       Astra Zeneca R&D Lund
Christel Krøigaard                   Aarhus Universitet
Torben Laursen                       Aarhus Universitet
Maja Laursen                         Lægemiddelstyrelsen
Trine Meldgaard Lund                 Københavns Universitet
Marie Lund                           GlaxoSmithKline Pharma A/S
Pernille Lyngholm-Kjærby             Norpharma A/S
Nils Magnuson                        Aarhus Universitet
Vladimir Matchkov                    Aarhus Universitet
Ian McGrath                          University of Glasgow
Michael J. Mulvany                   Aarhus Universitet
Ove A. Nedergaard                    Syddansk Universitet
Signe Neustrup                       Københavns Universitet
Lars Peter Nielsen                   Aarhus Universitet
Elise Røge Nielsen                   Aarhus Universitet
Rasmus Steen Pedersen                Syddansk Universitet
Morten Engholm Pedersen              Aarhus Universitet
Lisa Bürgel Pedersen                 Institut for Rationel Farmakoterapi
Tonny Studsgaard Petersen            LEO Pharma A/S
Caroline Pontoppidan                 Bispebjerg Hospital
Birgitte Klindt Poulsen              Aarhus Universitet
Christian Bo Poulsen                 Syddansk Universitet
Sofie Gry Pristed                    Ålborg Sygehus
Mette Rasmussen                      Københavns Universitet
Lene Reuther                         Bispebjerg Hospital
Bjørn Richelsen                      Århus Sygehus
Mette Rosenkilde                     Københavns Universitet
Jørgen Rungby                        Aarhus Universitet
Nina Drøjdahl Ryg                    Odense Universitetshospital
Jens Schou
Thue Schwartz                        Københavns Universitet
Ulf Simonsen                         Aarhus Universitet
Maren Skau                           Bispebjerg Hospital
Niels Skjærbæk                       Bioneer A/S
Jesper Sonne                         Bispebjerg Hospital
Claus Stage                          Bispebjerg Hospital
Eva Aggerholm Sædder                 Bispebjerg Hospital
Steffen Thirstrup                    Lægemiddelstyrelsen
Jane Tidemand                        Pfizer ApS
Hans Villendrup                      Roche A/S
Signe Østoft                         Bispebjerg Hospital
Mathilde Aalling                     Aarhus Universitet


                            - 19 -
Noter




 - 20 -
- 21 -
Dansk Selskab for
Farmakologi, Toksikologi og Medicinalkemi

				
DOCUMENT INFO