N Acetyl Cysteine (NAC) Helps Break Down Mucus

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Postby notasperfectasyou » Fri Jan 29, 2010 8:56 am

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NAC lowers MMP-9s

Postby jackD » Sat Jan 30, 2010 9:46 pm

I like NAC because it lowers mmp-9s.
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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]
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Postby jimmylegs » Sun Jan 31, 2010 4:49 am

so does zinc. reduce mmp-9s that is. part of what NAC does is combat the oxidative stress of zinc deficiency. optimize zinc status, you need less NAC, and your mmp-9s come down.

Free Radical Research
2006, Vol. 40, No. 1, Pages 75-84 , DOI 10.1080/10715760500312305

α-Lipoic acid and N-acetyl cysteine prevent zinc deficiency-induced activation of NF-κB and AP-1 transcription factors in human neuroblastoma IMR-32 cells [jl note: in vitro]

This work investigated the capacity of α-lipoic acid (LA) and N-acetyl-l-cysteine (NAC) to reduce zinc deficiency-induced oxidative stress, and prevent the activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), and the cross-talk between both activated cascades through β-Transducin Repeat-containing Protein (β-TrCP)... Thus, LA and NAC can reduce the oxidative stress associated with zinc deficiency and the subsequent triggering of NF-κB- and AP-1-activation in neuronal cells.
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There are two METALS that are a problem for MS folks.

Postby jackD » Sun Jan 31, 2010 10:06 am

There are two METALS that are a problem for MS folks.

ZINC and IRON

Some ZINC is good and necessary for good health however HIGH levels of ZINC is highly suspected of causing MS. Several "hot clusters" of MS have been found around locations where high levels of zinc were being released.

I do not think it would be wise for a person with MS to take ZINC supplements beyond 25 mg (167 %DV) that is in most multivitamins.

I think this may have something to to with MMP formation. All 27 types of MMPs have a zinc at the "business end" and use it to cut our Myelin into little pieces by breaking the hydrogen bonds. I think that the body may adapt to the high levels of ZINC by making LOTS of "very agressive" MMPs.

MMPs levels are elevated JUST BEFORE and DURING an MS attack.

jackD
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: J Neuroimmunol. 1997 Feb;72(2):155-61.

Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an
overview.

Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE,
Gearing AJ.

British Biotech Pharmaceuticals Limited, Cowley, Oxford, UK.

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process.

MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.

Publication Types:
Review
Review, Tutorial

PMID: 9042108 [PubMed - indexed for MEDLINE]
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1: Arch Environ Health. 2001 Sep-Oct;56(5):389-95.

Comment in:
Arch Environ Health. 2002 Jul-Aug;57(4):383; author reply 383.

A multiple sclerosis cluster associated with a small, north-central Illinois
community.

Schiffer RB, McDermott MP, Copley C.

Department of Neuropsychiatry, Texas Tech University Health Sciences Center,
Lubbock 79430, USA. psyrbs@ttuhsc.edu

The authors investigated a reported incidence cluster of multiple sclerosis (MS)cases in a small, north-central Illinois community to determine validity and statistical significance. DePue, Illinois--a small, north-central Illinois community--has previously been the site of significant environmental heavy-metal exposure from a zinc smelter. Significant contamination of soil and water with zinc and other metals has been documented in this community during the time period of interest. In the mid-1990s, several cases of MS were reported to the
Illinois Department of Public Health within the geographic limits of this
community. Available medical records from purported MS cases reported to the Illinois Department of Public Health were reviewed, and living individuals were seen and examined. Statistical analyses were conducted with clinically definite MS cases; onset dates were determined by first symptom, and expected incidence rates were determined from published epidemiologic studies. Nine new cases of clinically definite MS occurred among residents of DePue, Illinois, during the period between 1971 and 1990. Seven of the 8 living subjects included in the final analyses were examined by one author (RS).

The computed incidence rate deriving from these cases within DePue Township, Illinois, represented a statistically significant excess of new MS cases over expected. During the period from 1971 through 1990, a significant excess of MS cases occurred within the population of DePue, Illinois.

Significant exposure of this population to mitogenic trace metals, including zinc, was also documented during this time period.

PMID: 11777019 [PubMed - indexed for MEDLINE]
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Neurology. 1994 Feb;44(2):329-33.

A genetic marker and family history study of the upstate New York multiple sclerosis cluster.
Schiffer RB, Weitkamp LR, Ford C, Hall WJ.

Department of Neurology, University of Rochester School of Medicine and Dentistry, NY 14642.

We report nine additional cases of new-onset multiple sclerosis (MS) among employees of an upstate New York manufacturing plant that uses zinc as a primary metal. These cases, identified during the decade 1980 to 1989, had clinical onset of the disease between 1979 and 1987. The new cases confirm the increased incidence of MS previously reported in the plant population for the 1970 to 1979 decade. The MS subjects in this occupationally based cluster do not seem different from other MS patients with regard to rates of familial MS or the frequencies of alleles for human leukocyte (HLA-DR) antigens or transferrin. The frequency distribution of alleles for transferrin (an iron- and zinc-binding protein) may differ in these and other MS subjects compared with controls.

PMID: 8309585 [PubMed - indexed for MEDLINE]


Neurology. 1987 Oct;37(10):1672-7.

Multiple sclerosis and the workplace: report of an industry-based cluster.
Stein EC, Schiffer RB, Hall WJ, Young N.

Department of Preventive and Community Medicine, University of Rochester School of Medicine and Dentistry, NY 14642.

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.

PMID: 3658175 [PubMed - indexed for MEDLINE]
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To little Zinc BAD, just enough GREAT, too much ZincVERY BAD

Postby jackD » Sun Jan 31, 2010 10:14 am

It seems that zinc is low in the white matter of MS folks, so making sure
that you get a100% supply does make sense.

However I do not think that MS folks should exceed 30 mg daily as a supplement. A 100 % dose would be 15 mg.

A chelated form of zinc called zinc monomethionine (zinc bound with the
amino acid methionine) is sold under the trademark OptiZinc has been found
to have antioxidant activity comparable to that of Vitamin C, Vitamin E, and
beta-carotene. It is readily absorbed by the body in this form.

Too much zinc can cause MS by increasing numbers/intenstity of activity of MMPs.

The main component that does the myelin damage is the MMP-9s using the Zinc as a 'knife".

http://home.ix.netcom.com/~jdalton/Yongrev.pdf
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(see fig 2 and narrative on page 505)
METALLOPROTEINASES IN BIOLOGY AND PATHOLOGY OF
THE NERVOUS SYSTEM

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Postby jimmylegs » Sun Jan 31, 2010 5:51 pm

the 'optimal' serum zinc, based on averages in healthy controls (hundreds and hundreds of them) is 18.2 umol/L

armed with that info, anyone who is supplementing at doses like 30 mg per day can get a test and that way they'd know if the dosage was effective for them personally.

keeping in mind, patients may have to push to get the actual result with units from the doc.. in my experience docs are more likely to say "it's normal" as if that's somehow good, even when the result is in the 'ms part' of the normal range.
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NAC also lowers the levels of GLUTAMATE

Postby jackD » Mon Feb 01, 2010 10:11 pm

NAC also lowers the levels of GLUTAMATE which in excess in is deadly to neurons. This elevated levels of GLUTAMATE is a characteristic of the 2nd stage of MS.
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http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf
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Postby jimmylegs » Tue Feb 02, 2010 5:24 am

and apparently, when zinc is deficient, there can be an abnormal release of glutamate in the body. although i can't tell from this abstract alone whether a high potassium 'push' is required to initiate the glutamate release, or not.

Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan
Résumé / Abstract
The mechanism of the abnormal increase in extracellular glutamate concentration in the hippocampus induced with 100 mM KCl in zinc deficiency is unknown. In the present study, the changes in glutamate release (exocytosis) and GLT-1, a glial glutamate transporter, expression were studied in young rats fed a zinc-deficient diet for 4 weeks. Exocytosis at mossy fiber boutons was enhanced as reported previously and GLT-1 protein was increased in the hippocampus. The enhanced exocytosis is thought to increase extracellular glutamate concentration. However, the basal concentration of extracellular glutamate in the hippocampus was not increased by zinc deficiency, suggesting that GLT-1 protein increased serves to maintain the basal concentration of extracellular glutamate. The enhanced exocytosis was attenuated in the presence of 100 μM ZnCl2, which attenuated the abnormal increase in extracellular glutamate induced with high K+ in zinc deficiency. The present study indicates that zinc attenuates abnormal glutamate release in zinc deficiency. The enhanced exocytosis was also attenuated in slices from zinc-deficient rats administered Yokukansan, a herbal medicine, in which the abnormal increase in extracellular glutamate induced with high K+ was attenuated. It is likely that Yokukansan is useful for prevention or cure of abnormal glutamate release. The enhanced exocytosis in zinc deficiency is a possible mechanism on abnormal increase in extracellular glutamate in the hippocampus induced with high K+.
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