Author Topic: Dr. Theo publishes paper on inhibition of Mast Cells  (Read 1251 times)

Thegodofpleasure

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Dr. Theo publishes paper on inhibition of Mast Cells
« on: May 04, 2011, 05:27:39 AM »
Can anyone get hold of the full text of the following paper, which appears to be a further development based on what Dr. Theo reported in his presentation at the SoK workshop ?

Quote
Amitriptyline and Prochlorperazine Inhibit Proinflammatory Mediator Release From Human Mast Cells: Possible Relevance to Chronic Fatigue Syndrome

Clemons, Anthony BS1; Vasiadi, Magdalini BS2; Kempuraj, Duraisamy PhD3; Kourelis, Taxiarchis MD4; Vandoros, Gregory BS5; Theoharides, Theoharis C. MD, PhD6

Journal of Clinical Psychopharmacology:
June 2011 - Volume 31 - Issue 3 - pp 385-387
doi: 10.1097/JCP.0b013e3182196e50

garcia

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #1 on: May 04, 2011, 09:27:51 AM »
I wouldn't mind seeing this too if anyone can get hold of it please!

Many thanks!
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Tango

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #2 on: May 04, 2011, 10:48:51 AM »
It's a letter to the editor and from Tufts, ie. Coffin country.
"I suspect there have been a number of conspiracies that never were described or leaked out. But I suspect none of the magnitude and sweep of Watergate." Woodward

"I would favor any name that does not impose (or give the appearance of imposing) taxonomic preconceptions on the nomenclature." Coffin

Gerwyn

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #3 on: May 04, 2011, 11:57:58 AM »
Can anyone get hold of the full text of the following paper, which appears to be a further development based on what Dr. Theo reported in his presentation at the SoK workshop ?

Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: A link to neurogenic skin disorders.
 
 Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC.
 
 Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
 
 Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and are associated with increased numbers and activation of mast cells which release vasoactive, nociceptive, and proinflammatory mediators. Nontraumatic acute psychological stress by immobilization has been shown to induce mast cell degranulation in the rat dura and colon. Moreover, intradermal injection of corticotropin-releasing hormone (CRH) or its analogue urocortin (10(-5)-10(-7) M) induced skin mast cell degranulation and increased vascular permeability. Here, we investigated the effect of acute immobilization stress on skin mast cell degranulation by light microscopy and electron microscopy. Immobilization for 30 min resulted (P < 0.05) in degranulation of 40.7 +/- 9.1% of skin mast cells compared to 22.2 +/- 7.3% in controls killed by CO(2) or 17.8 +/- 2.4% in controls killed by pentobarbital. Pretreatment intraperitoneally (ip) with antiserum to CRH for 60 min prior to stress reduced (P < 0.05) skin mast cell degranulation to 21.0 +/- 3. 3%. Pretreatment with the neurotensin (NT) receptor antagonist SR48692 reduced (P < 0.05) mast cell degranulation to 12.5 +/- 3.4%, which was significantly (P < 0.05) below control levels. In animals treated neonatally with capsaicin to deplete their sensory neurons of their neuropeptides, such as substance P (SP), mast cell degranulation due to immobilization stress was reduced to about 15%. This is the first time that stress has been shown to trigger skin mast cell degranulation, an action not only dependent on CRH, but apparently also involving NT and SP. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory skin disorders such as atopic dermatitis, neurogenic pruritus, or psoriasis, which are induced or exacerbated by stress. Copyright 1999 Academic Press.
 
 PMID: 10469524 [PubMed - indexed for MEDLINE] 

garcia

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #4 on: May 05, 2011, 12:07:57 PM »
"Not everything that counts can be counted, and not everything that can be counted counts." Albert Einstein
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Thegodofpleasure

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #5 on: May 05, 2011, 02:52:37 PM »
It's a letter to the editor and from Tufts, ie. Coffin country.

Whilst he is at the same academic institution, I don't think that Dr Theo has anything  to do with the Undertaker.

His research work, which is helping to define the full extent of the involvement of mast cells in all sorts of inflammatory processes, is fascinating :  http://www.mastcellmaster.com/

garcia

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #6 on: May 07, 2011, 12:08:22 PM »
Having read the letter more closely they say:

Quote
"The concentration of AMI and PRO shown here to effectively inhibit
mast cell secretion is approximately 10 times higher than what might be expected
from the maximal daily dose
(eg, assuming 1 compartment model for an 80 kg
subject, the AMI maximum dose of 150 mg would yield a serum level of 6 KM).
However, brain mast cells may be more susceptible to the action of AMI than the
human cultured LAD2 leukemic mast cells."

So right now, the mechanism seems to be more theoretical than what is actually known to happen at the dosages that patients would normally take (to compound this, doses for AMI in ME/CFS are usually a lot lower than those prescribed for depression).

The do show however:

Quote
that AMI and PRO can decrease intracellular calcium ion levels.
« Last Edit: May 07, 2011, 12:10:31 PM by garcia »
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Thegodofpleasure

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #7 on: May 07, 2011, 03:48:32 PM »
Quote
"The concentration of AMI and PRO shown here to effectively inhibit
mast cell secretion is approximately 10 times higher than what might be expected
from the maximal daily dose
(eg, assuming 1 compartment model for an 80 kg
subject, the AMI maximum dose of 150 mg would yield a serum level of 6 KM).
However, brain mast cells may be more susceptible to the action of AMI than the
human cultured LAD2 leukemic mast cells."


Thanks for posting the paper Garcia  :)

Just to be clear, are they saying that we would need to take 10 times the normally recommended daily dosage of Amitriptyline and /or Prochlorperazine in order to effectively inhibit the mast cell derived proinflammatory cytokines / chemokines etc. ?

garcia

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Re: Dr. Theo publishes paper on inhibition of Mast Cells
« Reply #8 on: May 07, 2011, 03:58:44 PM »
Just to be clear, are they saying that we would need to take 10 times the normally recommended daily dosage of Amitriptyline and /or Prochlorperazine in order to effectively inhibit the mast cell derived proinflammatory cytokines / chemokines etc. ?

Yes, although obviously it would be crazy to exceed the maximum level of the drug, and they are not actually recommending that.

What they are saying is more like: "The maximum dosages used normally are insufficient to have much effect on the particular type of mast cells studied, but it's possible that the mast cells in the brain are more sensitive, in which case this is how those drugs may be helping ME/CFS."
"Not everything that counts can be counted, and not everything that can be counted counts." Albert Einstein
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