[olsen]

(this article is written in Spanish, and thru luck I was able to find the computer function that translated it (the resultant english translation is not entirely succesful, though one is able to "get the message". the following is an excerpt from the article. the second part is the abstract from the study itself)

http://www.que.es/sevilla/2009121211...ue-nuevas.html
"award given to...Ciberned investigator,...Sevillian young Mary Hidalgo.

...the investigation... also (included) Alberto Pascual as first signatory, on the progressive loss of certain neurons in the brain that appear in diseases neurodegenerative and published in magazines in 2008 'Nature' and 'Neuroscience'.

This neuronal death consequence is an alteration of the connections between neurons, which leads to the emergence of some of the symptoms of these diseases. The GDNF is a protein that manages to keep the survival of certain types (of neurons), although to date not much is known about the mechanism of action in neurons.

For study the role of This brain-derived neurotrophic factor, this study group generated eliminated in mice the GDNF protein during adult life. "With the mouse we demonstrated" GDNF really is essential for the survival of certain Neuronal populations in the brain of adult mice, since without this protein leaks neurons in certain regions of the "brain", he added.

"These regions" affected by the lack of GDNF match the areas damaged in disease Parkinson, what makes this interesting animal model for the study of "Biology of these neurons", concluded.



Nature Neuroscience 11, 755 - 761 (2008)
Published online: 8 June 2008 | doi:10.1038/nn.2136

http://www.nature.com/neuro/journal/...s/nn.2136.html

Absolute requirement of GDNF for adult catecholaminergic neuron survival
Alberto Pascual1,2,3, María Hidalgo-Figueroa1,3, José I Piruat1,2, C Oscar Pintado1, Raquel Gómez-Díaz1,2 & José López-Barneo1,2





GDNF is a potent neurotrophic factor that protects catecholaminergic neurons from toxic damage and induces fiber outgrowth. However, the actual role of endogenous GDNF in the normal adult brain is unknown... We have generated a conditional GDNF-null mouse to suppress GDNF expression in adulthood, hence avoiding the developmental compensatory modifications masking its true physiologic action. After Gdnf ablation, mice showed a progressive hypokinesia and a selective decrease of brain tyrosine hydroxylase (Th) mRNA, accompanied by pronounced catecholaminergic cell death, affecting most notably the locus coeruleus, which practically disappears; the substantia nigra; and the ventral tegmental area. These data unequivocally demonstrate that GDNF is indispensable for adult catecholaminergic neuron survival and also show that, under physiologic conditions, downregulation of a single trophic factor can produce massive neuronal death.

[pegleg]

olsen

How did you do that (the translation)? I need to use that function sometimes.

Yes, one can replace missing or deficient dopamine cells synthetically with medication, or by transplanting cells, or "stimulating" what cells one has left (DBS), but if you do not have the GDNF (growth hormone), the degeneration continues

Thhis is a good article - thanks.

Peggy (I hated that other photoo (my avatar) so I changed it - I made it myself in the bathroom one day lol. )

[paula_w]

Madelyn - what a find! Thank you! Now who is keeping us from getting it?

paula

[pegleg]

Did you know that the *catechol - whatever it is, is why they made Comtan (which means also in Stalevo)? Lately, about 15 minutes after I take Stalevo, I go off bad, then come back up to "normal." If I take just Sinemet or Parcopa, I don't have that down time. So why take Entacapone at all? (Entacapone is the generic name for Comtan and the Comtan in Stalevo) - Because it extends the life and efficacy of Sinemet (aka carbidopa/Levodopa). Tasmar is another brand name of a very similar drug, but a little stronger (Tolcapone is its generic name.) It was taken off the market due to deaths (yes, death from a toxic liver)

Hmmmm? I should get off that stuff. My neurologist said to take no more than 3 pills a day. And you should always take it with your dopaminergic medication.

And if I take too much Stalevo, man do I have dyskinesia. The 100/200 is too big for me, and the 25/200 is not enough. I am on a new dosage - 33.7/200

The most common side effects of STALEVO are unwanted or uncontrollable movements (known as dyskinesia), nausea, diarrhea, excessive muscle movements (known as hyperkinesia), harmless discoloration of urine, sweat and/or saliva; diminished or slow movements (known as hypokinesia), abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Some of the more serious side effects may include severe diarrhea, severe dyskinesia, hallucinations, other mental disturbances, orthostatic hypotension (low blood pressure), rhabdomyolysis (a muscle disease), and symptoms resembling neuroleptic malignant syndrome (a condition characterized by fever and muscle stiffness).


Peg

* I went back and looked up that 75 cent word that I was tr ying to remember iin my first sentence. Here it is from the Comtan website:
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT), used in the treatment of Parkinson's Disease as an adjunct to levodopa/carbidopa therapy.
And remember, all that Stalevo is composed of is Comtan and carbidopa/Levodopa. (but the less pills I have to swallow, the better. )

[paula_w]

madelyn,

if i understand what you have there correctly, i understand why some people called gdnf a cure. so logically, would'nt it be helpful to check the number of years with pd for all in the gdnf trials and check it against those who did well with it? They [study authored by mandel] are going to give it to people early on in the disease because they "contend" this will only work with them...when those who need it most are further along.

Where is the proof for this 'contending' that it works only in early stage?

paula

[paula_w]

peg,

comtan causes dyskinesia for me, so I've never taken stalevo. I believe the combination drugs were created with good intentions but also from a colossal lack of understanding of the nature of pd. they take away what little control we have with our condition from hour to hour.

but i know there are others who like it .
paula

Originally Posted by pegleg

Did you know that the *catechol - whatever it is, is why they made Comtan (which means also in Stalevo)? Lately, about 15 minutes after I take Stalevo, I go off bad, then come back up to "normal." If I take just Sinemet or Parcopa, I don't have that down time. So why take Entacapone at all? (Entacapone is the generic name for Comtan and the Comtan in Stalevo) - Because it extends the life and efficacy of Sinemet (aka carbidopa/Levodopa). Tasmar is another brand name of a very similar drug, but a little stronger (Tolcapone is its generic name.) It was taken off the market due to deaths (yes, death from a toxic liver)

Hmmmm? I should get off that stuff. My neurologist said to take no more than 3 pills a day. And you should always take it with your dopaminergic medication.

And if I take too much Stalevo, man do I have dyskinesia. The 100/200 is too big for me, and the 25/200 is not enough. I am on a new dosage - 33.7/200

The most common side effects of STALEVO are unwanted or uncontrollable movements (known as dyskinesia), nausea, diarrhea, excessive muscle movements (known as hyperkinesia), harmless discoloration of urine, sweat and/or saliva; diminished or slow movements (known as hypokinesia), abdominal pain, dizziness, constipation, fatigue, pain, and hallucinations. Some of the more serious side effects may include severe diarrhea, severe dyskinesia, hallucinations, other mental disturbances, orthostatic hypotension (low blood pressure), rhabdomyolysis (a muscle disease), and symptoms resembling neuroleptic malignant syndrome (a condition characterized by fever and muscle stiffness).


Peg

* I went back and looked up that 75 cent word that I was tr ying to remember iin my first sentence. Here it is from the Comtan website:
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT), used in the treatment of Parkinson's Disease as an adjunct to levodopa/carbidopa therapy.
And remember, all that Stalevo is composed of is Comtan and carbidopa/Levodopa. (but the less pills I have to swallow, the better. )

[olsen]

Hi Peg, you asked how I translated the article: I do not know what system worked for this page, though I have since discovered the "google translate" feature. madelyn