Right acting/right thinking TIMP-1 gene transfer?


Regarding the concept of MMP-9s being responsible for most myelin damage, I must confess that I have never really given all the TIMPs-1 a clean bill of health.

They are suppose to insure that the MMP-9s only eat the BAD STUFF.(dead/damaged/dying things)

What if they are at fault and are directing the MMP-9s to the Myelin for LUNCH?????

Traitors for sure - but is there reasonable evidence to even suspect them???

jackD

I can imagine that transplanting some "Right-thinking/Right-Acting" TIMP-1 producing genes that generate TIMP-1s which are proven MYELIN PROTECTORS would also be a good idea.

(I reserve the rights of Intellectual Discovery despite this public posting here.)


jackD


1: Circulation. 2004 Sep 14;110(11 Suppl 1):II180-6.

Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer
effectively treats ischemic cardiomyopathy.

Jayasankar V, Woo YJ, Bish LT, Pirolli TJ, Berry MF, Burdick J, Bhalla RC,
Sharma RV, Gardner TJ, Sweeney HL.

Department of Surgery, University of Pennsylvania School of Medicine,
Philadelphia, Pa 19104-4283, USA

BACKGROUND: Enhanced activity of matrix metalloproteinases (MMPs) has been
associated with extracellular matrix degradation and ischemic heart failure in
animal models and human patients. This study evaluated the effects of MMP
inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy.

METHODS AND RESULTS: Rats underwent ligation of the left anterior descending
coronary artery with direct intramyocardial injection of replication-deficient
adenovirus encoding TIMP-1 (n=8) or null virus as control vector (n=8), and
animals were analyzed after 6 weeks. Both systolic and diastolic cardiac
function was significantly preserved in the TIMP-1 group compared with control
animals (maximum left ventricular [LV] pressure: TIMP-1 70+/-10 versus control
56+/-12 mmHg, P<0.05; maximum dP/dt 2697+/-842 versus 1622+/-527 mmHg/sec,
P<0.01; minimum dP/dt -2900+/-917 versus -1195+/-593, P<0.001). Ventricular
geometry was significantly preserved in the TIMP-1 group (LV diameter 13.0+/-0.7
versus control 14.4+/-0.4 mm, P<0.001; border-zone wall thickness 1.59+/-0.11
versus control 1.28+/-0.19 mm, P<0.05), and this was associated with a reduction
in myocardial fibrosis (2.36+/-0.87 versus control 3.89+/-1.79 microg
hydroxyproline/mg tissue, P<0.05). MMP activity was reduced in the TIMP-1
animals (1.5+/-0.9 versus control 43.1+/-14.9 ng of MMP-1 activity, P<0.05).

CONCLUSIONS: TIMP-1 gene transfer inhibits MMP activity and preserves cardiac
function and geometry in ischemic cardiomyopathy. The reduction in myocardial
fibrosis may be primarily responsible for the improved diastolic function in
treated animals.

TIMP-1 overexpression is a promising therapeutic target for
continued investigation.

PMID: 15364860 [PubMed - indexed for MEDLINE]

Ok I got my ALA today. I took one as soon as I got home.

The label: Lipoic Acid (Alpha) 300mg GR.

Says I can take it once or twice a day. Hrm! I guess it depends on how I respond on 1 a day, and if I don't find that enough, increase to 2?

I have 60 capsules to play with in any case from the compounding lab.

Day 2 ALA. I pulled an 'all nighter' at the ER over the cyst ordeal, and when I got home took 1 capsule of ALA. Napped for 2 hours, got up, took a second capsule as I can take 2 per day, and was go go go since.

I think ALA IS truly helping the mouth now. Still too soon to tell, but its 7 pm and normally I'd be taking .25mg of Clonazepam by now, but I haven't felt the need to (no significant mouth pain).

Day 3. My geographic tongue is coming back, go figure.

Amitriptyline free now for 3 days as well! My hair is no longer falling out when I run my fingers through it, thank goodness. Also my mouth is no dry as a badly when I wake up.

Took 1 capsule of ALA this morning. I had not eaten yet, and I do find it causes a bit of stomach discomfort in my case. I may instead try taking it with a meal or after one.