Malaria treated with glycosaminoglycan / metal chelation 
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 Malaria treated with glycosaminoglycan / metal chelation

Public release date: 29-Sep-2006

Contact: Katarina Sternudd

Karolinska Institutet

New treatment for severe malaria
The most dangerous form of malaria is difficult to treat and claims two
million lives a year. Now, researchers at Karolinska Institutet in
Sweden have developed a powerful new weapon against the disease.

Severe anaemia, respiratory problems and encephalopathy are common and
life-threatening consequences of serious malaria infection. The
diseases are caused when the malaria bacteria P.falciparium infects the
red {*filter*} cells, which then accumulate in large amounts, blocking the
flow of {*filter*} in the capillaries of the brain and other organs.

The reason that the {*filter*} cells conglomerate and lodge in the {*filter*}
vessels is that once in the {*filter*} cell the parasite produces proteins
that project from the surface of the cell and bind with receptors on
other {*filter*} cells and on the vessel wall, and thus act like a glue. The
challenge facing scientists has been to break these bonds so that the
infected {*filter*} cells can be transported by the {*filter*} stream into the
spleen and destroyed.

The research group, which is headed by Professor Mats Wahlgren, has now
developed a substance that prevents infected {*filter*} cells from binding
in this way. The substance also releases {*filter*} cells already bound.
Using this method, scientists have been able to treat severe malaria in
rats and primates effectively; it now remains to be seen whether these
results can be replicated in people.

"There's often a lack of ability to treat people suffering from severe
malaria," says Professor Wahlgren. "We've developed a substance that
might be able to help these patients."

Previously, an anti-coagulant called heparin was used in the treatment
of severe malaria. Heparin was able to release the {*filter*} cells, but it
was soon withdrawn when it was shown that the substance caused internal
bleeding. The new substance is a development of heparin, and has the
important difference of having no effect on normal {*filter*} coagulation.

The study, which is jointly financed by Swedish International
Development Cooperation Agency and Dilafor AB, is to be presented on 29
September in PLoS Pathogens.

"Release of sequestered malaria parasites upon injection of a
glycosaminoglycan," Anna M. Vogt, Fredrik Pettersson, Kirsten Moll,
Cathrine Jonsson, Johan Normark, Ulf Ribacke, Thomas G. Egwang,
Hans-Peter Ekre, Dorothe Spillmann, Qijun Chen and Mats Wahlgren, PLoS
Pathogens, September 2006, Vol. 2, Issue 9, e100.

For further information, please contact:

Professor Mats Wahlgren
Phone: +46-8-524 872 77, +46-70-556 12 46

Postdoc Anna Vogt
Phonel: +46-8-457 25 09, +46-70-320 48 73


these molecules may function as metal chelators

Glycoconj J. 2003 Feb;20(2):133-41.  Links

Glycosaminoglycans reduce oxidative damage induced by copper (Cu(+2)),
(Fe(+2)) and hydrogen peroxide (H(2)O(2)) in human fibroblast cultures.

Campo GM, D'Ascola A, Avenoso A, Campo S, Ferlazzo AM, Micali C, Zanghi
Calatroni A.

Department of Biochemical, Physiological and Nutritional Sciences,
School of
Medicine, University of Messina, Policlinico Universitario, 98125

Acid glycosaminoglycans (GAGs) antioxidant activity was assessed in a
fibroblast culture system by evaluating reduction of oxidative
damage.Three different methods to induce oxidative stress in human skin

fibroblast cultures were used. In the first protocol cells were treated
CuSO(4) plus ascorbate. In the second experiment fibroblasts were
exposed to
FeSO(4) plus ascorbate. In the third system H(2)O(2) was utilised.The
exposition of fibroblasts to each one of the three oxidant systems
inhibition of cell growth and cell death, increase of lipid
evaluated by the analysis of malondialdehyde (MDA), decrease of reduced

glutathione (GSH) and superoxide di{*filter*}ase (SOD) levels, and rise of
dehydrogenase activity (LDH).The treatment with commercial GAGs at
doses showed beneficial effects in all oxidative models. Hyaluronic
acid (HA)
and chondroitin-4-sulphate (C4S) exhibited the highest protection.
However, the
cells exposed to CuSO(4) plus ascorbate and FeSO(4) plus ascorbate were
protected by GAGs compared to those exposed to H(2)O(2).These outcomes
the antioxidant properties of GAGs and further support the hypothesis
these molecules may function as metal chelators. Published in 2004.

PMID: 15001845 [PubMed - in process]



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Fri, 20 Mar 2009 21:08:00 GMT
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