NeuroTalk Support Groups - More symptoms even on Avonex

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- Multiple Sclerosis (https://www.neurotalk.org/multiple-sclerosis/)

- - More symptoms even on Avonex (https://www.neurotalk.org/multiple-sclerosis/48128-symptoms-avonex.html)

Quote:

Originally Posted by Curious (Post 304394)

i'm sorry you do not like our policies and guidlines jack. ones you agreed to when you joined.

we provide a forum, unlike many others where you don't see porn and other spam.

having to actually particapate with only 10 posts isn't much. it does keep people from joining just to post links.

Thanks to ALL for saying hello and welcome. I know I will make the 10 post qualification however it did take me 2,756 posts on Braintalk before I was banned as jackD. I hope to make it to at least 3,000 here. I was reborn again as Braindead on Braintalk. I now have 338 posts as Braindead.

jackD AKA Braindead

Jack N Dalton

amn is over 5000, you should be safe. :D she does bribe the mods. :rolleyes:

heck..i'm over 9000 and doc still puts up with me. :p

Welcome to Neurotalk, Jack and, so far, I really do mean that. Don't expect us to be rude, as, they have always been, at that other place.

I remember your good posts, but, unfortunately, I remember some of your umm...not so good, posts, as well. Please treat us with the same respect you would expect for yourself, and all will be great.:)

I have always been interested in the MMP-9 theory, and finding something to counteract the damage it does. Have you found anything safe, we can add to our supplement regimine, that has helped to accomplish this noble feat?

Again, Welcome Friend and let us know if there is anything we can do to support you, in your fight against MS. We are even allowed to have some good clean fun, here......visit the Stumble Inn (cute huh?) and find out.:D

Quote:

Originally Posted by SallyC (Post 304713)

Sally

I am glad to be here and hope to contribute a lot of practical helpful info.

I have some VERY GOOD info on how to reduce/lower those nasty MMP-9s populations but must wait until I have 10 posts before posting it because I am trying to fool them into thinking I am a nice guy and I must show some pics and .pdf stuff on my web storage area and some links.

But you just wait until I get my 10 postings and the REAL JACK will appear!!!

jackD

jack, be sure you read the guidlines about posting articles. especially about copyright. we can't post full articles. just a few sentences and the link MUST be included.

we had some backlash from from some authors.

i fyou have any questions, please pm me. oh...and pm the links to the ones you posted. i don't want to have to pull them. the edit time may have expired for you to include them.

Thanks for all of the information. It is going to take me a while to read through it!

I have Optic Neuritis and 5 children to take care of. Not much time to read! But I do appreciate the help.

Quote:

Originally Posted by slskckjebw (Post 304882)

Thanks for all of the information. It is going to take me a while to read through it!

I have Optic Neuritis and 5 children to take care of. Not much time to read! But I do appreciate the help.

Yep! I started with a BIG ON attack and loss all color vision in my right eye. For me it was at age 52. This was a big suprise to both me and the Drs at Johns Hopkins. Men do not usually get MS at that age. The ON did get rid of all those darn RED traffic lights. I got to work much faster in those days. I had repeated ON attacks every winter Jan-Feb but started Avonex and lots of supplements like VIT D3, green tea extract, alpha lipoic acid etc etc and that cycle came to a halt.

Keep up the fight and you can overcome the other big MS problems like cognitive loss and excessive fatigue.

jackD

If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness.

http://www.cnsforum.com/commentedite...9/default.aspx

Also getting the most activity from the least amount of near natural (human) interferon like Avonex will usually result in MUCH LESS neutralizing antibody formation (2-5% vrs 20-26%).

Unfortunately for MS folks (MMP-9s) also like to cut a hole in our BBB Blood Brain Barrier and then enter the brain and cut our myelin into three components that the other hungry characters like to dine on. This mechanism of destruction caused by excessive agressive MMP-9s is a good target for reduction and should reduce MS damage if lowered a tad. Actual abstracts and one major study on my web page are provided below.

http://home.ix.netcom.com/~jdalton/Yongrev.pdf

SEE FIGURE 2 and MS info on page 505

Things that reduce MMP-9s (AKA gelatinase B)
This list of GOOD "things" for MS should seem familiar - This is WHY???

VIT D3 .................................REDUCES MMP-9s

RESVERATROL (Grape Skin Extract) ...REDUCES MMP-9s
(NOT GRAPE SEED EXTRACT)

GREEN TEA EXTRACT(EGCGs)... REDUCES MMP-9s

ALPHA LIPOIC ACID (R-lipoic/ R-Dihdro-LipoicAcid) ... REDUCES MMP-9s

NAC N-Acetyl-L-Cysteine .......REDUCES MMP-9s

STATIN DRUGS (i.e Zocor) .....REDUCES MMP-9s

Omega-3s (ie Fish oil) ...........REDUCES MMP-9s

Minocycline/Doxycycline.........REDUCES MMP-9s

Curcumin.............................REDUCES MMP-9s

Pycnogenol (Pine bark extract)..REDUCES MMP-9s

Chondroitin sulfate (CS) and CS plus glucosamine sulfate (GS) ..REDUCES MMP-9s

Interferon Betas 1a/1b...........REDUCES MMP-9

(of course Steroids ....REDUCES MMP-9s)

***NOTE*** ( gelatinase B = MMP-9) ***NOTE***

I have lots more information on this MMP - MS - INTERFERON-beta connection and will elaborate it if there is some interest in this subject here.

Jack n dalton - jackD

Quote:

Lancet Neurol. 2003 Dec;2(12):747-56.

Functional roles and therapeutic targeting of gelatinase B(MMP-9) and chemokines in
multiple sclerosis.

Opdenakker G, Nelissen I, Van Damme J.
GO, IN, and JVD are at the Rega Institute for Medical Research, University
of
Leuven, Belgium

Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown
cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of
autoreactive lymphocytes, and skewing of the extracellular proteinase
balance, are targets for new therapies.

Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was
recently shown to degrade interferon beta, one of the drugs used to treat
MS.

Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B(MMP-9)
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and
inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression
of gelatinase B(MMP-9), may become effective treatments of MS, alone or in
combination with interferon beta. This may allow interferon beta to be used
at lower doses and prevent side-effects.

PMID: 14636780 [PubMed - in process]

1: Brain. 2003 Jun;126(Pt 6):1371-81.

Gelatinase B/matrix metalloproteinase-9(MMP-9) cleaves interferon-beta and is a
target for immunotherapy.

Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology,
University of Leuven, Leuven, Belgium.

Parenteral administration of interferon (IFN)-beta is one of the currently
approved therapies for multiple sclerosis. One characteristic of this
disease is the increased production of gelatinase B(MMP-9), also called matrix
metalloproteinase (MMP-9) Gelatinase B is capable of destroying the
blood-brain barrier, and of cleaving myelin basic protein into
immunodominant and encephalitogenic fragments, thus playing a functional
role and being a therapeutic target in multiple sclerosis. Here we
demonstrate that gelatinase B(MMP-9) proteolytically cleaves IFN-beta, kills its
activity, and hence counteracts this cytokine as an antiviral and
immunotherapeutic agent. This proteolysis is more pronounced with
IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline
minocycline, which has a known blocking effect in experimental autoimmune
encephalomyelitis, an in vivo model of acute inflammation in multiple
sclerosis, and other MMP inhibitors prevent the in vitro degradation of
IFN-beta by gelatinase B(MMP-9). These data provide a novel mechanism and rationale
for the inhibition of gelatinase B(MMP-9) in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B(MMP-9) inhibitors with better
and lower pharmacological formulations of IFN-beta may reduce the
side-effects of treatment with IFN-beta, and is therefore proposed for
multiple sclerosis therapy and the immunotherapy of viral infections.

PMID: 12764058 [PubMed - indexed for MEDLINE]

1: J Neuroimmunol 2002 Oct;131(1-2):104-14

Alpha lipoic acid inhibits T cell migration into the spinal cord and
suppresses and treats experimental autoimmune encephalomyelitis.

Marracci GH, Jones RE, McKeon GP, Bourdette DN.
Department of Neurology, Oregon Health and Science University, Portland, OR
97201, USA.

Oxidative injury may be important to the pathogenesis of multiple sclerosis
(MS). We tested the antioxidant alpha lipoic acid (ALA) in an experimental
murine model of MS, experimental autoimmune encephalomyelitis (EAE). ALA was
administered to SJL mice 7 days after immunization with proteolipid protein
(PLP) 139-151 peptide. Mice that received 5-100 mg/kg/day of ALA had
dose-dependent reductions in their 10-Day Cumulative Disease Scores (10-Day
CDS) by 23-100%. Minimal inflammation, demyelination and axonal loss
occurred in the spinal cords (SC) of ALA-suppressed mice, and there was a
marked reduction in CD3+ T cells and CD11b+ monocyte/macrophage cells within
the SC. Mice treated with ALA (100 mg/kg/day) commencing on the first day of
clinical EAE had a significant reduction in 10-Day CDS. SC of ALA-treated
mice had reduced demyelination and axonal loss and a rapid reduction in CD3+
T cells. In vitro, ALA and its reduced form, dihydrolipoic acid, inhibited
the activity of matrix metalloproteinase-9 (MMP-9) in a dose-dependent
fashion. ALA is highly effective at suppressing and treating EAE and does so
by inhibiting T cell trafficking into the SC, perhaps by acting as a matrix
metalloproteinase inhibitor.

PMID: 12458042 [PubMed - indexed for MEDLINE]

1: Neurology 2002 Oct 8;59(7):990-7
Comment in:
Neurology. 2002 Oct 8;59(7):970-1.

Statins as immunomodulators: comparison with interferon-beta 1b in MS.

Neuhaus O, Strasser-Fuchs S, Fazekas F, Kieseier BC, Niederwieser G, Hartung
HP, Archelos JJ.
Department of Neurology, Multiple Sclerosis Research Group,
Karl-Franzens-Universitat, Graz, Austria.
BACKGROUND: Recent data suggest that statins may be potent immunomodulatory
agents. In order to evaluate the potential role of statins as
immunomodulators in MS, the authors studied their immunologic effects in
vitro and compared them to interferon (IFN)beta-1b. METHODS: Peripheral
blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated
patients with relapsing-remitting MS or from healthy donors (HD) and T cells
were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3
in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or
statins plus IFN beta-1b. The authors analyzed proliferative activity of T
cells and B cells, cytokine production and release, activity of matrix
metalloproteinases (MMP), and surface expression of activation markers,
adhesion molecules, and chemokine receptors on both T and B cells. RESULTS:
All three statins inhibited proliferation of stimulated PBMC in a
dose-dependent manner, with simvastatin being the most potent, followed by
lovastatin and mevastatin. IFN beta-1b showed a similar effect; statins and
IFN beta-1b together added their inhibitory potentials. Furthermore, statins
reduced the expression of activation-induced adhesion molecules on T cells,
modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and
downregulated chemokine receptors on both B and T cells. Besides strong
anti-inflammatory properties, statins also exhibited some proinflammatory
effects. CONCLUSIONS:
Statins are effective immunomodulators in vitro that merit evaluation as
treatment for MS.

PMID: 12370451 [PubMed - indexed for MEDLINE]

1: QJM 2002 Dec;95(12):787-796

Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR
genotype: mechanisms for inflammatory damage in chronic disorders?
Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D,
Aganna E, Price CP, Boucher(2) BJ.
Departments of. Clinical Biochemistry, Diabetes and Metabolic Medicine and.
Haematology, Barts and The London, Queen Mary's School of Medicine and
Dentistry, University of London and. Department of Cardiology, 'Barts and
The London' NHS Trust, London, UK.

BACKGROUND:Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are
risk factors for several disorders with inflammatory components, including
coronary heart disease (CHD) and diabetes, though the mechanisms involved
are unclear. Aim: To examine the hypothesis that vitamin D status modulates
the matrix metalloproteinase (MMP) system in a population with a high
prevalence of vitamin D deficiency, a situation affecting susceptibility to
CHD and diabetes.

DESIGN:
Prospective cross-sectional, interventional and embedded studies. METHODS:
Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were
measured during studies of vitamin-D deficiency as a risk factor for type 2
diabetes and CHD in 171 healthy British Bangladeshi adults, free of known
diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood
pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1,
folate and homocysteine were measured. Vitamin-D-deficient subjects were
re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were
measured in 41 subjects halfway through 5-year follow-up. Independent
determinants of circulating concentrations of MMP9, TIMP-1 and CRP were
assessed by multiple regression analysis.

RESULTS: Vitamin D status was the sole determinant of circulating MMP9
(inversely) and an independent determinant of CRP (inversely). Determinants
of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype
(TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%)
concentrations followed vitamin-D supplementation. DISCUSSION: Vitamin-D
insufficiency is associated with increased circulating MMP2,9 and CRP,
correctable by supplementation. This finding provides a possible mechanism
for tissue damage in chronic inflammatory conditions, including CHD and
diabetes.

PMID: 12454321 [PubMed - as supplied by publisher]

1: Acta Pharmacol Sin. 2003 Nov;24(11):1167-71.

Resveratrol inhibits matrix metalloproteinase-9 transcription in U937 cells.

Li YT, Shen F, Liu BH, Cheng GF.

Department of Pharmacology, Institute of Materia Medica, Chinese Academy of
Medical Sciences and Peking Union Medical College, Beijing 100050, China.

AIM: To examine the inhibitory effect of resveratrol on matrix
metalloroteinase-9 (MMP-9) and explore its mechanism. METHODS: MMP-9
activity was analyzed by gelatin zymography; MMP-9 protein was detected by Western
blot; MMP-9 mRNA expression was investigated by RT-PCR. Activation of activator
protein -1 (AP-1) was measured by electrophoretic mobility shift assay
(EMSA).

RESULTS: MMP-9 activity in U937 cells increased significantly after exposed
to PMA at 10 nmol/L for 24 h without FCS (P<0.01). Resveratrol at 1 and 10
micromol/L showed significant inhibition on MMP-9 activity (P<0.05 and
P<0.01, respectively). Western blot and RT-PCR experiments displayed that MMP-9
protein (P<0.01) and mRNA expression (P<0.01) increased significantly in PMA-treated
U937 cells. Resveratrol at 1 and 10 micromol/L showed inhibitory effects on
MMP-9 protein production and MMP-9 mRNA expression (P<0.05). The activation
of AP-1 induced by PMA was also extensively inhibited by resveratrol at 0.1, 1,and
10 micromol/L. CONCLUSION: The inhibitory effect of resveratrol on MMP-9
activity may be partly through suppression of activation of nuclear
transcription factor AP-1, and inhibition of MMP-9 mRNA expression and MMP-9
protein production.

PMID: 14627504 [PubMed - in process]

Since lots of MS folks think that taking "Grape Seed Extract" is good and I have posted the opposite I will provide my reason for having my opinion.

IF and ONLY if we accept that increasing GAMMA INTERFERON is BAD for MS folks will my argument prove sound.

I would hope that everyone can accept this as a fact.

Some Gamma Interferon at low levels is necessary for good health and myelin repair.

The medical literature shows that ADDING/INCREASING Gamma Interferon has worsened MS folks in clinical studies.

jackD

Quote:

Clin Diagn Lab Immunol 2002 Mar;9(2):470-6

Grape seed extract activates Th1 cells in vitro.

Nair N, Mahajan S, Chawda R, Kandaswami C, Shanahan TC, Schwartz SA.

Division of Allergy, Immunology, and Rheumatology, Department of Medicine, State University of New York at Buffalo and Kaleida Health, 14203, USA.

Although flavonoids manifest a diverse range of biological activities, including antitumor and antiviral effects, the molecular mechanisms underlying these activities await elucidation. We hypothesize that the flavonoid constituents of a proprietary grape seed extract (GSE) that contains procyandins exert significant antiviral and antitumor effects, by inducing production of the Th1-derived cytokine gamma interferon (IFN-gamma) by peripheral blood mononuclear cells) from healthy donors. Our results show that GSE significantly induced the transcription of IFN-gamma mRNA as demonstrated by reverse transcription-PCR but had no effect on the Th2-derived cytokine interleukin-6. The enhancing effect of GSE on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracytoplasmic IFN-gamma as well as the synthesis and secretion of IFN-gamma.

Our results demonstrate that the potentially beneficial immunostimulatory effects of GSE may be mediated through the induction of IFN-gamma.

PMID: 11874895 [PubMed - indexed for MEDLINE

MMP Arthritis connection

This thread is a bit of a mess.. so I will get off the main track without fear of destroying the beauty of this messy thread.

This study from Lebanon shows that MMPs do the actual damage in BOTH rheumatoid arthritis (RA) and osteoarthritis (OA).

I have found that my MMP reduction program of supplements has done wonders at reducing mr OA arthritis. I have had both kneees operated on and things were still so bad I walked around my house on crutches.

My finger joints were red and swollen and VERY VERY SORE.

MY thumb was almost useless because of the pain generated at the base of the thumb when I used my right hand.

Since I started my MMP-9 reduction program I have had NO pain for the last 6 yes!!! Yes - no more crutches, no red finger joints, no more annual shots in the knees!!

You must also reduce interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and maybe IL-12 also. That is no BIG deal because some of the MMP-9 reduction "thingies" does this also quite well.

jackD

P.S. For more info go to PubMed and search on "MMP arthritis".

P.P.S. - It is real shame that this Medical folks cannot find ways to reduce these nasty MMPs. I had no problem and have discovered two more "thingies" that reduce MMP-9s in the las two weeks. I will post them later after more research.

http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Quote:

Front Biosci. 2006 Jan 1;11:529-43.

Matrix metalloproteinases: role in arthritis.

Burrage PS, Mix KS, Brinckerhoff CE.

Department of Biochemistry, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.

The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury.

In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix.

The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage.

In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction.

:eek:Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints.

Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints.

:rolleyes:To date, however, no effective clinical inhibitors exist. Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.

PMID: 16146751 [PubMed - indexed for MEDLINE]

http://groups.google.com/group/alt.s...3d3011b530e3b6