Læknaneminn - 01.04.2002, Blaðsíða 65

stærsti áhrifaþátturinn á styrk S-ferritíns hjá virkum
blóðgjöfum.
Umræöa:
Þörfin fyrir fleiri virka blóðgjafa eykst sífellt. Þess
vegna er náið eftirlit með blóðgjöfum lykilatriði til að
huga að heilsu og öryggi þeirra svo að þeir skili sér
aftur. Járnbirgðirnar eru þar helsti áhrifaþátturinn, en
sé gripið inní tímanlega t.d. með því að lengja tímann
á milli blóðgjafa og ráðleggja járninntöku ætti að vera
hægt að kornast fyrir þau vandkvæði.
Experimental autoimmune encephalomyelitis
in the Dark Agouti rat
-treatment with intravenous polyclonal human
immunoglobulin G
Þorsteinn H. Ástráðsson' and Signe Humle Jargensen2.
'University of lceland, Faculty of Medicine.
2Copenhagen University Hospital (Rigshospitalet),
MS Research Unit.
Introduction:
Experimental autoimmune encephalomyelitis (EAE)
is an animal model of multiple sclerosis (MS) that can
be induced in the Dark Agouti (DA) rat by irnmun-
ization with spinal cord homogenate (SCH)
emulsified in Freund's adjuvant. Results from clin-
ical trials and animal studies indicate that pooled
polyclonal immunoglobulin G (IVIg) given intraven-
ously can be effective in the treatment of both MS and
EAE. The objective of the study was to establish a
model of chronic relapsing EAE in the DA rat for use
in later experiments and also to test an lVlg infusion
procedure and evaluate the therapeutic effect of IVIg
on EAE severity.
Materials and methods:
Twenty male DA rats were immunized with an
emulsion of syngeneic SCH and Freund's adjuvant
(incomplete (IFA) or complete (CFA)) in the tail base
either intradermally (i.d.) or subcutaneously (s.c.).
The rats were examined and scored daily following
immunization for clinical signs of EAE on a scale of
0-5 (0-no signs;l-loss of tail tonus;2-moderate hind-
limb paresis;2.5-severe hindlimb paraparesis;3-comp-
lete hindlimb paralysis;4-complete paralysis of hind-
limbs with forelimb paresis;5-moribound state or
death). Ten of these animals received infusions into a
tail vein (10 minute or 45 minute infusions) of either
human polyclonal IgG (h-IgG) or placebo on days 0
and 1 post immunization.
Results:
Four rats were immunized i.d. with SCH+CFA wher-
eof 3 died within 12 days. Mean maximal score was
4.5((1.0). Six rats were immunized with SCH+IFA, 3
rats i.d.(l died) and 3 rats s.c. Mean maximal scores
for the i.d. and s.c. groups were 4.0(( 1.0) and 1,3(( 1.5)
respectively. Ten rats were immunized with SCH+IFA
and then received h-IgG or placebo. The mean max-
imal score in the h-IgG group was 1.3((1.0) and
2.0(( 1.2) in the placebo group.
Discussion:
The use of CFA resulted in a severe EAE with a high
mortality rate and CFA was therefore excluded from
further studies. It could also be concluded that the
disease courses following s.c. immunizations with IFA
were too mild but when immunized i.d. with IFA the
rats exhibited an EAE suitable for our later ex-
periments. The animals that received h-IgG had rnild-
er disease courses than those receiving placebo but
this was not statistically significant. The fast in-
fusions were well tolerated but the prolonged anest-
hesia required for the slow infusions resulted in
marked weight loss which makes the fast infusions
more preferable.
Áhrif fólatskorts á DNA-skemmdir í
B-eitilfrumulínum með og án stökkbreytingar í
BRCA2 geni
Þórður Guðmundsson
Inngangur:
BRCA2 genið er talið gegna hlutverki í viðgerðum á
tvíþátta DNA brotum. Fólatskortur veldur auknum úr-
asílvillum í DNA og auknum tvíþátta DNA brotunr í
kjölfarið. Markmið rannsóknarinnar var að kanna
hvort fólatskortur leiði til rneiri DNA skemmda í B-
eitilfrumulínum með stöklcbreytingu í BRCA2 en í B-
eitilfrumulínum sem ekki hafa stökkbreytinguna.
Efniviöur og aðferöir:
B-eitilfrumulínur úr fjórum einstaklingum voru rækt-
aðar í fólatlitlu æti. Líkt var eftir fólatskorti með notk-
un flúóródeoxýúrídínis sem hindrar nýtingu fólats til
myndunar týmídíns. Sýni voru tekin úr rækt eftir 24,
48, og 72 ldst. DNA skemmdir voru mældar með
halaaðferðinni (comet assay / single cell gel electroph-
oresis) sem greinir einþátta- og tvíþáttabrot í erfðaefn-
inu. Ensímið úrasíl DNA glýkósýlasi var notað til að
klippa á úrasíl villur í erfðaefninu og rnynda DNA
brot.
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