wanted to add that Pycnogenol (Pine Bark Extract) lowers MMP-9 quite well. I take it to help with my swollen right foot. I have some nasty Venous Insufficiency because of numerous unecessary surgeries to my leg.

It is well known that Pine Bark extract (Pycnogenol) can "FIX" this problem. The fact it prevents the condition from killing folks like me is GOOD ENOUGH FOR ME!!!!!!!!!!!@

I no longer have severe PAIN nor INFECTIONS(Cellulites), INFECTED BLACK TOES ETC ETC.

jackD


1: Free Radic Biol Med. 2004 Mar 15;36(6):811-22.

Antioxidant activity and inhibition of matrix metalloproteinases by metabolites
of maritime pine bark extract (pycnogenol).

Grimm T, Schafer A, Hogger P.

Institut fur Pharmazie und Lebensmittelchemie, Bayerische
Julius-Maximilians-Universitat, Wurzburg, Germany.

The procyanidin-rich maritime pine bark extract Pycnogenol has well-documented
antioxidant and anti-inflammatory activity. After oral administration of
Pycnogenol two major metabolites are formed in vivo,
delta-(3,4-dihydroxyphenyl)-gamma-valerolactone (M1) and
delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone (M2). We elucidated the
effects of these metabolites on matrix metalloproteinases (MMPs) and determined
their antioxidant activity to understand their contribution to the effects of
maritime pine bark extract. We discovered strong inhibitory effects of M1 and M2
toward the activity of MMP-1, MMP-2, and MMP-9. On a microgram-per-milliliter
basis both metabolites appeared more active than Pycnogenol. The metabolites
were more effective than their metabolic precursor (+)-catechin in MMP
inhibition. On a cellular level, we detected highly potent prevention of MMP-9
release by both metabolites, with concentrations of 0.5 microM resulting in
about 50% inhibition of MMP-9 secretion. M1 was significantly more effective in
superoxide scavenging than (+)-catechin, ascorbic acid, and trolox, while M2
displayed no scavenging activity. Both metabolites exhibited antioxidant
activities in a redox-linked colorimetric assay, with M1 being significantly
more potent than all other compounds tested.

Thus, our data contribute to thecomprehension of Pycnogenol effects and provide
a rational basis for its use in prophylaxis and therapy of disorders
related to imbalanced or excessive MMP activity.

PMID: 14990359 [PubMed - indexed for MEDLINE]

1: J Inflamm (Lond). 2006 Jan 27;3:1.

Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human
volunteers after ingestion of maritime pine bark extract (Pycnogenol).

Grimm T, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Hogger P.

Institut fur Pharmazie und Lebensmittelchemie, Bayerische
Julius-Maximilians-Universitat, Wurzburg, Germany. hogger@pzlc.uni-wuerzburg.de

French maritime pine bark extract (Pycnogenol) displays a variety of
anti-inflammatory effects in vivo. Aim of this study was to determine whether
human plasma after oral intake of Pycnogenol contains sufficient concentrations
of active principles to inhibit key mediators of inflammation. Blood samples
from seven healthy volunteers were obtained before and after five days
administration of 200 mg Pycnogenol per day. Plasma samples statistically
significantly inhibited matrix metalloproteinase 9 (MMP-9) release from human
monocytes and NF-kappaB activation. Thus, we provide evidence that bioavailable
active principles of Pycnogenol exert anti-inflammatory effects by inhibition of
proinflammatory gene expression which is consistent with documented clinical
observations. We suggest that our ex vivo method is suitable to substantiate
molecular pharmacological mechanisms of complex plant extracts in a more
focussed and rational way compared to in vitro studies by taking into account
the processes of absorption and metabolism.

PMID: 16441890 [PubMed]

1: Clin Appl Thromb Hemost. 2004 Oct;10(4):373-7.

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with
pycnogenol.

Belcaro G, Cesarone MR, Rohdewald P, Ricci A, Ippolito E, Dugall M, Griffin M,
Ruffini I, Acerbi G, Vinciguerra MG, Bavera P, Di Renzo A, Errichi BM,
Cerritelli F.

Department of Biomedical Sciences, Irvine2 Vascular Lab, G D'Annunzio University
and San Valentino Vascular Screening Project (Pe), Faculty of Motory Sciences,
L'Aquila University, Italy. cardres@pe.abol.it

The aim of this study was to evaluate the occurrence of deep venous thrombosis
(DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral
anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management
SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to
high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211
were included (33 were excluded for several reasons due to logistic problems)
and 198 completed the study; 13 subjects were lost for follow-up at the end of
the flight, all for non-medical problems (i.e., for difficult connections). All
subjects were scanned within 90 minutes before the flight and within 2 hours
after disembarking. Subjects were supplemented with 100 mg Pycnogenol per
capsule. Treatment subjects received two capsules between 2 and 3 hours before
flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL
of water and one capsule the next day. The control group received comparable
placebo at the same intervals. The flight duration was on average 8 hours and 15
minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five
thrombotic events (one DVT and four superficial thromboses) while only
nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15%
vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13
failures in the control group (eight lost to follow up + five thrombotic events)
of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events)
in the treatment group (p<0.025). No unwanted effects were observed.

In conclusion, this study indicates that Pycnogenol treatment was effective in
decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high
risk subjects, during long-haul flights.
PMID: 15497024 [PubMed - indexed for MEDLINE]

1: Angiology. 2006 Oct-Nov;57(5):569-76.

Rapid relief of signs/symptoms in chronic venous microangiopathy with
pycnogenol: a prospective, controlled study.

Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G, Ricci
A, Gizzi G, Ippolito E, Fano F, Dugall M, Acerbi G, Cacchio M, Di Renzo A, Hosoi
M, Stuard S, Corsi M.

Irvine2 Vascular Lab and Physiology, Department of Biomedical Sciences, G
'Annunzio, Chieti-Pescara University, San Valentino Vascular Screening Project,
Faculty of Motory Sciences, L'Aquila University, Italy.

The aim of this study was to investigate the clinical efficacy of oral
Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous
insufficiency. Patients with severe venous hypertension (chronic venous
insufficiency, ankle swelling) and history of venous ulcerations were treated
with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times
daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was
included in the treatment group and 18 equivalent patients were observed as
controls (no treatment during the observation period). All 21 patients (age 53
years; range, 42-60 years; M:F=11:10) in the treatment group completed the
8-week study. Also the 18 controls completed the follow-up period. There were no
drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68)
with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no
differences in ambulatory venous pressure or refilling time between the
treatment and control patients. The duration of the disease-from the first
signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all
Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated
a progressive decrease in skin flux, indicating an improvement in the level of
microangiopathy; a significant decrease in capillary filtration; a significant
improvement in the symptomatic score; and a reduction in edema. There were no
visible effects in controls.

In conclusion, this study confirms the fast
clinical efficacy of Pycnogenol in patients with chronic venous insufficiency
and venous microangiopathy. The study indicates the significant clinical role of
Pycnogenol in the management, treatment and control of this common clinical
problem. The treatment may be also useful to prevent ulcerations by controlling
the level of venous microangiopathy.

PMID: 17067979 [PubMed - indexed for MEDLINE]

NAC (N-Acetyl-L-Cysteine) also lowers MMP-9s as well as some other nasty things.

I take 600 mg a day (Vitamin Shoppe $17.17 for 100 capsules)

jackD

1: J Clin Endocrinol Metab. 2003 Apr;88(4):1723-9.

N-Acetyl-cysteine inhibits phospholipid metabolism, proinflammatory cytokine
release, protease activity, and nuclear factor-kappaB deoxyribonucleic
acid-binding activity in human fetal membranes in vitro.

Lappas M, Permezel M, Rice GE.

Department of Obstetrics and Gynecology, University of Melbourne, and Mercy
Perinatal Research Center, Mercy Hospital for Women, East Melbourne, 3002
Victoria, Australia. mlappas@unimelb.edu.au

The production of reactive oxygen species (ROS), prostaglandins (PGs),
proinflammatory cytokines, and proteases has been implicated in the pathogenesis
of term and preterm labor. The nuclear factor-kappaB (NF-kappaB) transcription
pathway is activated by ROS and is a key regulator of PGs, proinflammatory
cytokine release, and protease activity. N-Acetyl-cysteine (NAC) is an
antioxidant that through its ability to scavenger ROS suppresses NF-kappaB
DNA-binding activity and resultant gene expression. The aim of this study was to
elucidate the effect of NAC on NF-kappaB DNA-binding activity, phospholipid
metabolism, cytokine release, and protease activity from human fetal membranes.
Human amnion and choriodecidua (n = 9 separate placentas) were treated with 0
(control), 5, 10, or 15 mM NAC in the presence of 10 micro g/ml
lipopolysaccharide. After 6-h incubation, the tissues were collected, NF-kappaB
DNA binding activity was assessed by gel shift binding assays, and matrix
metalloproteinase-9 and urokinase-type plasminogen activator activity were
determined by zymography. The incubation medium was collected and assayed for
type II phospholipase A(2) tissue content, IL-6, IL-8, TNFalpha, and
8-isoprostane release by ELISA. The release of PGF(2alpha) was measured by RIA.
Treatment of fetal membranes with NAC significantly suppressed
lipopolysaccharide-stimulated type II phospholipase A(2) release and content;
PGF(2alpha), IL-6, IL-8, TNFalpha, and 8-isoprostane release; and matrix
metalloproteinase-9 and urokinase-type plasminogen activator enzyme activity and
suppressed NF-kappaB DNA-binding activity (by ANOVA, P < 0.05). The data
presented in this study demonstrate that NAC inhibits an NF-kappaB-activated
pathway and subsequent phospholipid metabolism, proinflammatory cytokine
release, and protease activity in human fetal membranes.

PMID: 12679464 [PubMed - indexed for MEDLINE]
1: Biofactors. 1999;10(2-3):187-93.

N-Acetyl-cysteine inhibition of encephalomyelitis Theiler's virus-induced nitric
oxide and tumour necrosis factor-alpha production by murine astrocyte cultures.

Molina-Holgado F, Hernanz A, De la Fuente M, Guaza C.

Neural Plasticity Unit, Instituto Cajal, CSIC, Madrid, Spain.

The pathological mechanisms that cause central nervous system (CNS) dysfunction
in most neurological diseases are not well established. Theiler's murine
encephalomyelitis virus (TMEV) is known to interact with cells of the CNS and
its intracerebral inoculation to susceptible mice strains causes neurological
disorders resembling multiple sclerosis (MS). In this study, we reported that
primary astrocyte cultures from SJL/J susceptible mice when infected with TMEV
released important amounts of nitrites (NO2-) to the culture medium, as measured
in the supernatants 24 hours after infection. In addition, we observed an
increment in the production of tumour necrosis factor alpha (TNF-alpha) by
susceptible SJL/J strain derived astrocytes infected with TMEV. The treatment
with the thiolic antioxidant N-acetyl-cysteine partially suppressed the
virus-stimulated production of nitric oxide and TNF-alpha, in a dose response
fashion. These results indicate that during viral infection astrocytes are an
important cellular source of nitric oxide and TNF-alpha, substances which play
important roles during CNS inflammatory events. The effects of the antioxidant
N-acetyl-cysteine, modulating the production of the above compounds by
TMEV-infected astrocytes may be a significant factor in preventing CNS
demyelination.
PMID: 10609881 [PubMed - indexed for MEDLINE]

Very recent study on Quercetin & MS &MMP-9s and how it helps Interferon Beta treatment.

Lowering MMP-9s is GOOD for ALL folks with MS (PERIOD) regardless of DMD.

Remember folks HIGH levels of MMP-9s destroy Interferon Betas drugs.

Hope you all realize that having a nice RED apple each day is a GOOD source of Quercetin as well as the entire Onion family.

I start the day with a MOTT'S - RED DELICIOUS APPLE -Extra Fancy and real pretty from the state of Washington.

I also take a Quercetin supplement later in the day.

jackD



1: J Neuroimmunol. 2008 Oct 14.

Quercetin and interferon-beta modulate immune response(s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients.

Sternberg Z, Chadha K, Lieberman A, Hojnacki D, Drake A, Zamboni P, Rocco P, Grazioli E, Weinstock-Guttman B, Munschauer F.
Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, United States.

The study is aimed to determine the role of quercetin (3,3'4',5,7-pentahydroxy flavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMC) isolated from multiple sclerosis (MS) patients and from normal healthy subjects.

PBMC proliferation in the presence or absence of these drugs was determined and the production of proinflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 were assessed in the culture supernatants.

Quercetin reduced, in a dose-dependent manner, the proliferation of PBMC and modulated the level of IL-1beta and TNF-alpha released by PBMC in the culture supernatants.

Quercetin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. Quercetin, when combined with IFN-beta, had additive effects in modulating TNF-alpha and MMP-9. These immunomodulatory responses to quercetin were similar between MS patients and healthy control (HC) subjects.

PMID: 18926575

Simplified SUMMARY one-two-three.


1-ONE. MMP-9s eat holes in the Blood Brain Barrier(BBB), they destroy myelin and cleave/inactivate Interferon drugs.

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

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

2 -TWO. REDUCE MMP-9s ANY way you can - using diet, supplements & secondary effects of other drugs.

It is a matter of risk, lifestyle, costs, personal preference and your ability to make decisions based upon incomplete and admittedly weak info.


Things that reduce MMP-9s (AKA gelatinase B)

QUERCETIN..........................REDUCES MMP-9s

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***


3-THREE. Cap other inflammatory components like IL-12, Gamma Interferon, TNF-a, IL-1 beta and glutamate excitotoxicity.Some of the above "things" also lower some of these. I will try to elaborate on this but I want to stay on the MMP-9s focus for now.

http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf


jackD

p.s. Sorry but understanding how MS progresses, a technical medical thing, is somewhat necessary to understand and appreciate this complementary approach. How MS progresses will be another NEW future thread. I am not concerned with the ULTIMATE CAUSE OF MS but only with how it progresses and the few processes that can be slowed to alter the disease progression.

There is a promising new version of NAC being developed.

The below is the company's recent press release

jackD

This could take forever to read through, but you seem to have done your research. It would be nice to have a place to discuss different ideas on vitamin/supplement/herb theories as it relates to symptom relief in MS. I'm not totally sold on meds.