In vivo and in vitro neurotoxic action of plasma ultrafiltrate from uraemic patients.
BACKGROUND
In order to investigate the aetiology of uraemic neuropathy, we evaluated the neurotoxic activity of plasma from uraemic patients. To this end we prepared a concentrate (1:1000) of 2-60 kDa MW compounds from paired filtration dialysis ultrafiltrate and evaluated its activity on peripheral nerve conduction in vivo and in vitro.


METHODS
The in vivo neurotoxicity was tested on rat sciatic nerve by intraneural injection of the uraemic concentrate, followed, 1 to 6 days later, by electrophysiological assessment of motor response and maximum conduction velocity. In vitro experiments were performed on isolated frog sciatic nerve in the presence of uraemic concentrate, and the neurotoxicity was evaluated from the rate of the decrease in the amplitude of the evoked maximal action potential.


RESULTS
In the in vivo experiments, the sciatic nerves injected with the uraemic concentrate showed a decrease in maximum conduction velocity and a progressive impairment in evoked motor response. In the in vitro experiments uraemic concentrate induced a dose-dependent neurotoxic effect.


CONCLUSIONS
Our study demonstrates the presence in plasma of uraemic patients of a compound of 2-60 kDa MW with neurotoxic activity.
Institute of Internal Medicine, Division of Nephrology 1, University of Padova, Italy.
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S
Cantaro
G
G
Zara
C
C
Battaggia
P L
PL
di Loreto
L
L
Calò
A
A
D'Angelo
G
G
Theophilidis
D000200:Action Potentials / Q000502:physiology; D000368:Aged; D000818:Animals; D001001:Anura; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007267:Injections; D018482:Muscle, Skeletal / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D010949:Plasma / Q000502:physiology; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014511:Uremia / Q000097:blood*
D009498:Neurotoxins