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Chlorure de lithium

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fti:
très intéressant a traduire désolé

http://www.scibx.com/scibx_main/20081009.html

fti:
salut a tous j'ai écris au docteur Shuxin li qui a fait l'étude sur le lithium au texas voila ça réponse

Dear guerdener

I am sorry to know you got spinal cord injury a few years ago. We recently found that Lithium partially promoted recovery in rodents with spinal cord injury, but we have not moved this drug to humans.  I knew that Lithium is on clinical trial for SCI patients in Hong Kong and China, but have not seen any results from their studies.  I will let you know if have further information on this.
Have a nice holiday.

Shuxin li

fti:
voila une explication de wise young sur le mécanisme du lithium très intéressons A TRADUIRE DESOLE



Lithium was first reported to have beneficial effects on spinal cord injury by Yick, et al. (2004) from Hong Kong University. They treated spinal cord hemisections with lithium and chondroitinase, alone and in combination with each other. The combination had the best results and the cut spinal tract showed regeneration.

Subsequently, we applied lithium to umbilical cord blood mononuclear cells (human and rat) and found that it stimulated the cells to proliferate (grow) so that after a week there would be 3-4x more cells in culture. When we injected the rats with lithium (subcutaneous because rats don't like the taste of lithium), we found that they markedly increased the number of transplanted neonatal rat blood or human umbilical cord blood mononuclear cells in the spinal cord at 2 weeks. The lithium did not stop immune rejection. All the cells were gone by 4 weeks after injury. We also found out that lithium strongly stimulated the cells to produce growth factors, including neurotrophins. However, we also found out that if we give the rats cyclosporin (CsA), to prevent immune rejection, it blocked the effects of lithium on cellular proliferation as well as neurotrophin production.

We recently completed a series of studies elucidating the mechanism of action of the lithium effects on stem cells. Lithium activates a number of phosphokinases and several phosphatases, all of which converge to inhibit a key enzyme called glycogen synthetase kinase 3-beta (GSK3-beta). This serine-threonine phosphokinase enzyme is responsible for phosphorylating and inactivating a number of nuclear factors that turn on genetic programs for growth, protection, and differentiation, particularly NFAT and Wnt/beta catenin. It turns out that these nuclear factors are activated by a serine-threonine phosphatase called calcineurin. So, lithium stops GSK3-beta inhibition of these nuclear factors but they need to be activated by calcineurin. It turns out that cyclosporin blocks calcineurin, explaining why it completely antagonized the lithium effects.

We therefore proposed to do a clinical trial where we will transplanted HLA-matched umbilical cord blood mononuclear cells into the spinal cords of people with chronic spinal cord injury and randomized them to lithium or no lithium. The therapeutic serum level of lithium is believed to be between 0.6 and 1.0 mM. The toxic levels start at 1.5 mM and higher. For that reason, it is critical that lithium be given with careful monitoring of serum lithium levels. For an adult, usually about a gram a day of lithium is necessary to get 0.6 mM levels. In any case, this must be titrated and managed by an doctor who is experienced with lithium use.

I am worried that you and your doctor don't know much about these drugs and that you are just using them because you have heard this or that about the drugs. The design of combination therapies is one of the most difficult tasks in the field and it is not something that you can just experiment with in this way and expect to get any significant results. Regarding the cell transplantation approach, I am quite skeptical that intravenous administration of cells or even intrathecal administration of cells are getting them into the right place in the spinal cord. I cannot even begin to evaluate the risks of combining these various therapies.

Wise.

fti:






A EFASE DESOLE

TDelrieu:
Patrick,

Le glycogen synthase kinase-3 (GSK-3) est une enzyme du corps impliquée dans le métabolisme du glycogène, et régule diverses fonctions cellulaires. L'étude ci-dessus montre que le Lithium inhibe l'action du "glycogen synthase kinase-3", ce qui a pour effet d'induire "une repousse descendante significative des axones corticospinaux et sérotonergiques dans la moelle épinière caudale et favorisent le rétablissement fonctionnel locomoteur".

Donc on parle là du Lithium seul.

Par contre, dans l'essai clinique prévue en 2009 par le Pr. Wise Young dans le cadre du ChinaSCInetwork, le Lithium sera combiné avec des cellules mononucléaires de sang ombilical ! 

:smiley:

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