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Article ID
1301200104
Author Dr. Eser Yildirim Sozmen Ege University, Faculty of
Medicine, Dept. of Biochemistry
Bornova-Izmir, Turkey
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Dr. Sozmen worked at the Lipid Research Laboratory
in the Department of Medicine at Manchester Royal Infirmary as a
fellow funded by FEBS-short term fellowship and IFCC-Professional
Scientific Exchange programme. During this fellow-ship, she worked
with Dr. Bharti Mackness under the guidance of Dr. Michael Mackness
and learned the methods to determine several enzymes and PON
genotyping as follows:
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CETP (cholesterol ester transfer protein)
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LCAT (lecithine cholesterol acyl transferase)
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PON 1 activity
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PON mass
PON genotyping (bath 55 and 192 polymorhisms)
Organophosphorus (OP) pesticides are the most
prevalent agents used (either by oral or inhalation means) in
suicide attempts in Turkey especially in the Aegean region where
cultivation is one of the main means of subsistence. The potential
effect of organo- phosphates depends upon the amount and form
ingested, the toxicity of the agent, the time lapse involved and a
variety of host factors. However, it has been observed that
patients have different clinical signs independent of the
environmental factors listed above. Serum paraoxonase (PON1) is an
enzyme located on HDL and it hydrolyses various substrates
including the organophosphate pesticides and lipid peroxides on
LDL. The amino acid polymorphism at position-192 (glutamine and
arginine) results in two allozymes (R and Q), which differ in their
hydrolytic activity towards paraoxon. Another polymorphism at amino
acid 55, which is a leucine (L) to methionine (M) substitution,
modulates PON1 activity independently of the 192 polymorphism. The
difference in individual clinical findings is clearly the most
important risk factor for susceptibility against OP's. These
differences seem to be closely related to PON1 activity and ON1
polymorphism since it has been shown that R-allele is more
efficient than the Q-allele in hydrolysing paraoxon in vitro. The
effect of PON1 polymorphism on the level of toxicity of the
patients exposed to OP is still obscure. The aim of the project was
to determine the link between possible individual risk factors
(age, PON1 activity, PON1 genotypes, serum PON1
Concentration, butyrylcholine esterase activity)
and prognosis in suicides with organosphosphorus pesticides.
During the period of October 1999-July 2000, 28
patients (men and women) were admitted to the Emergency Service at
Ataturk Research and Educational Hospital in Izmir/Turkey due to OP
poisoning. 26 of them drank a different amount of a variety of OP's
to attempt suicide, one used injection and one other was exposed to
OP's by inhalation. They were treated and monitored in the hospital
by a team led by Dr. B. Sozmen and Dr. L.Aslan. Their blood samples
were from them upon arrival. As a control group, 66 healthy persons
(men and women) matched for age and sex, volunteered to participate
in this study. Sera and buffy coats with EDTA of both groups were
kept in -80�C until sending them to Manchester Royal Infirmary.
Butyrylcholine esterase activities were determined using
butyrylthiocholin as substrate according to the method of Ellman et
al, at the Dept. of Biochemistry in Ege University. PON1 activities
were measured by the method proposed by Dr. Mackness et al using
paraoxon as a substrate. PON mass was also determined with an ELISA
method, at Lipid Research Laboratory in Dept. of Medicine of
Manchester Royal Infirmary. PON genotypes (for both polymorphism 55
and 192) were demonstrated in the same laboratory.
Allele frequencies of patients and controls are as
follows:
We observed an inhibition in PON1 activity as well
as BuChE activity due to exposure to OP pesticides, which was
independent of the type and dose of them. After the patients will
be evaluated for PON1 and BuchE activities again, we will discuss
our data.
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