X-Message-Number: 25067
Date: Wed, 17 Nov 2004 05:34:17 -0800 (PST)
From: Doug Skrecky <>
Subject: thiamin benefit for cryonics patients?

Diabetes Metab Res Rev. 2004 Jul-Aug;20(4):330-6
Thiamine and benfotiamine prevent increased apoptosis in endothelial
cells and pericytes cultured in high glucose.
  BACKGROUND: High glucose induces pathological alterations in small and
large vessels, possibly through increased formation of AGE, activation of
aldose reductase and protein kinase C, and increased flux through the
hexosamine pathway. We showed previously that thiamine and benfotiamine
correct delayed replication and increase lactate production in endothelial
cells subjected to high glucose. We now aim at verifying the effects of
thiamine and benfotiamine on cell cycle, apoptosis, and expression of
adhesion molecules in endothelial cells and pericytes, under high ambient
glucose. METHODS: Human umbilical vein endothelial cells and bovine
retinal pericytes were cultured in normal (5.6 mmol/L) or high (28
mmol/L) glucose, with or without thiamine or benfotiamine, 50 or 100
micro mol/L. Apoptosis was determined by two separate ELISA methods,
measuring DNA fragmentation and caspase-3 activity, respectively. Cell
cycle and integrin subunits alpha3, alpha5, and beta1 concentration were
measured by flow cytometry. RESULTS: Apoptosis was increased in high
glucose after 3 days of culture, both in endothelium and pericytes.
Thiamine and benfotiamine reversed such effects. Neither cell
cycle traversal nor integrin concentrations were modified in these
experimental conditions. CONCLUSIONS: Thiamine and benfotiamine correct
increased apoptosis due to high glucose in cultured vascular cells.
Further elucidations of the mechanisms through which they work could help
set the basis for clinical use of this vitamin in the prevention and/or
treatment of diabetic microangiopathy.

Ann Neurol. 2002 Aug;52(2):195-204
Cofactors of mitochondrial enzymes attenuate copper-induced death in
vitro and in vivo.
  Copper toxicity contributes to neuronal death in Wilson's disease and
has been speculatively linked to the pathogenesis of Alzheimer's and
prion diseases. We examined copper-induced neuronal death with the goal
of developing neuroprotective strategies. Copper catalyzed an increase in
hydroxyl radical generation in solution, and the addition of 20 microM
copper for 22 hours to murine neocortical cell cultures induced a
decrease in ATP levels and neuronal death without glial death. This
selective neuronal death was associated with activation of caspase-3 and
was reduced by free radical scavengers and Z-Val-Ala-Asp
fluoromethylketone, consistent with free radical-mediated injury leading
to apoptosis. Pyruvate dehydrogenase is especially vulnerable to
inhibition by oxygen free radicals, and the upstream metabolites,
pyruvate, phosphoenolpyruvate, and 2-phosphoglycerate were elevated
in cortical cells after toxic exposure to copper. One approach to
protecting pyruvate dehydrogenase from oxidative attack might be to
enhance binding to cofactors. Addition of thiamine, dihydrolipoic acid,
or pyruvate reduced copper-induced neuronal death. To test efficacy in
vivo, we added 1% thiamine to the drinking water of Long Evans Cinnamon
rats, an animal model of Wilson's disease. This thiamine therapy markedly
extended life span from 6.0 +/- 1.6 months to greater than 16 months.

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