Connective Tissue Disorders, Collagen and CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Re: Collagen shifts in vein walls found in CCSVI

Postby frodo » Fri Nov 04, 2011 9:00 am

Is this shift reported in jugular veins or also happens in small vessels?

Here there is an article reporting abnormal BBB permeability for "brain microvessel endothelial cells". There are others reporting BBB permeability for collagen-abnormal veins.

http://www.mendeley.com/research/brain- ... -capacity/

"The adhesion properties of brain microvascular endothelial cells (MVEC) and leukocytes derived from patients with multiple sclerosis (MS) were investigated. Leukocytes and brain MVEC from MS patients exhibited significantly higher adhesion capacity than the same cells isolated from normal donors. Flow cytometry showed that MS-derived brain MVEC constitutively expressed higher levels of ICAM-1 and contained an increased proportion of MHC class II positive cells than normal brain MVEC. In contrast, no difference was seen for vascular cell adhesion molecule-1 and endothelial cell leukocyte adhesion molecule-1. Circulating leukocytes from MS patients expressed higher levels of LFA-1, a ligand of intercellular adhesion molecule-1 (ICAM-1), than did normal leukocytes. The data presented here suggest that the ICAM-1/LFA-1 interaction may determine cytoadherence of leukocytes to brain MVEC in MS".
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Re: Endothelin1 and its affect on Collagen Types I and III

Postby Cece » Wed Nov 23, 2011 3:41 pm

bumped for jimmylegs
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Re: Collagen shifts in vein walls found in CCSVI

Postby Cece » Wed Nov 23, 2011 3:44 pm

bumped for jimmylegs :)

Really interesting stuff. There is also the question Dr. Beggs raised at the NY symposium in July, which is if the nonresponders to CCSVI treatment might have capillaries that have been thickened due to the effects of disordered flow, and therefore there is resistance at the intracranial capillary level, and therefore flow is still hindered despite effective treatment of the extracranial jugular stenoses.
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby Cece » Wed Nov 23, 2011 3:45 pm

maybe all these collagen threads could be merged into one? There's different information in each one.

again bumped for jimmylegs :)
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Re: Zamboni ISET .pdf online

Postby Cece » Wed Nov 23, 2011 3:53 pm

bumped for jimmylegs :)

Here was where I saw the material on the autopsy/vein graft tissue slide but it's no longer available. There was a sideways valve shown on venogram and then shown as a fixed tissue sample, after it was removed for a vein graft. Fascinating.
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Re: Endothelin1 and its affect on Collagen Types I and III

Postby jimmylegs » Wed Nov 23, 2011 4:05 pm

thx cece. the following came out of discussion on one of the stickies but belongs out in the general ccsvi area i suspect...
and so, looking at collagen/endothelin-1/magnesium/stents...

Structural alterations of the vascular wall in magnesium‐deficient mice. A possible role of gelatinases A (MMP‐2) and B (MMP) (mice)
http://www.jle.com/fr/revues/medecine/i ... icle.phtml
Magnesium ions are known to protect the cardiovascular system by preventing both calcium accumulation and connective damages, whereas magnesium deficiency induces cardiovascular damages [1, 2]. The vascular lesions of magnesium deficiency are characterized in various animal species by a severe degradation of the extra cellular matrix (ECM) of the connective tissue i.e. by edema, hypertrophy and hyperplasia of the intima, by a thinning and a fragmentation of the internal elastica, by edema, necrosis and hyperplasia of the media. These lesions are accompanied by calcification [3-5].
The integrity of the ECM involves a balance between the synthesis and organization of its structural constituents and their degradation by metalloendopeptidases belonging to the matrixin family [7, 8]. The most important of these endopeptidases belong to the matrix metalloproteinase (MMP) family which, to date, comprises at least 26 members. Among them, the gelatinases MMP-2 and MMP-9, are potent in their ability to cleave gelatins, denatured collagens (IV, V, VII, X), elastin, fibronectin, and TNF-α [6]. A recent report has revealed that MMP-2 can also cleave native collagen I [9] and collagen III [10]. However, it seems that the MMP are capable of degrading all the components of the ECM [11]. The activities of these extracellular metalloproteinases are controlled by specific naturally occurring inhibitors (TIMPs) [7, 11].
The magnesium-deficient diet used for 42 days in Swiss OF1 mice in the present assay, led as usual to a severe magnesium deficiency, since magnesium plasma levels were 4-fold decreased as compared to controls [16]. These conditions induced severe alterations of the 2 main connective fibers, elastin and collagens, as described previously by others [4, 5, 17].

Effect of magnesium sulfate on plasma endothelin-1 levels in normal and preeclamptic pregnancies.
http://www.ncbi.nlm.nih.gov/pubmed/1471664
We attempted to determine the effects of magnesium sulfate on: (1) endothelin-1 concentration in preeclampsia, preterm labor, and term pregnancy and (2) endothelin-1 release from human umbilical cord endothelial cells.
METHODS:
Plasma samples were prospectively collected from eight women with preeclampsia, six preterm labor patients, and eight term patients undergoing external cephalic version before and 2 hours after magnesium sulfate infusion.
RESULTS:
Magnesium sulfate infusion in preeclampsia lowered endothelin-1 levels compared with preinfusion values (6.6 +/- 3.81 before and 4.75 +/- 2.28 after infusion, p < 0.02).
CONCLUSION:
A significant reduction of endothelin-1 plasma levels after magnesium sulfate therapy is limited to preeclampsia. In contrast, this lowering effect was not exhibited in women without preeclampsia or in normal endothelial cells.
hmm needs some further digging then..

Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin (rats)
http://www.springerlink.com/content/481162444r825777/
We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines, IL-1, IL-6, and TNF-α together with signigicantly elevated levels of the endothelial cell-derived cytokine, endothelin, were detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency.

now if i can only find some good work involving more humans.

also, i ran across this again - i was sure i had already posted this somewhere but it's not coming up quickly, so here it is again and sorry if this is a repeat!:

Drug-Eluting Bioabsorbable Magnesium Stent
http://onlinelibrary.wiley.com/doi/10.1 ... 081.x/full
Current stent technology is based on the use of permanent implants that remain life long in the vessel wall, far beyond the time required for the prosthesis to accomplish its main goals of sealing dissection and preventing wall recoil. With the possibility to implant long vessel segments using antiproliferative drugs to prevent restenosis, the practice of transforming the coronary vessels into stiff tubes with a full metal jacket covering all side branches and being unable to adjust to the long-term wall changes, including wall remodeling with lumen ectasia becomes a serious concern. In this article, we describe the first biodegradable stent based on a magnesium alloy that allows controlled corrosion with release to the vessel wall and the blood stream of a natural body component such as magnesium with beneficial antithrombotic, antiarrhythmic, and antiproliferative properties. We also discuss the animal experiments and the initial clinical applications in 20 patients with implants below the knee, with final results soon to be released, and the plans for the first coronary study. The results of these last two studies will indicate whether the absence of a permanent implant and the antiproliferative properties shown in animals are sufficient to prevent the restenotic process in humans or whether the prosthesis must be modified by adding the biodegradable coating with conventional antiproliferative drugs.
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby jimmylegs » Wed Nov 23, 2011 4:13 pm

hey thanks - we should definitely be able to merge these. i will try it out :)
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Re: Zamboni ISET .pdf online

Postby jimmylegs » Wed Nov 23, 2011 4:20 pm

huh can't even find another copy out in the googlescape. i'll merge it regardless, thx.
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Re:

Postby frodo » Wed Nov 23, 2011 4:23 pm

OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients.

MATERIALS AND METHODS: A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects.

RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.



224% higher? and nobody has ever wondered why? and they still tell us the autoimmune theory as a proven fact? each time I read news like this one I feel depressed
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby jimmylegs » Wed Nov 23, 2011 4:54 pm

well at least we know that magnesium is likely to lower it, from the available evidence. more research would be nice.
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby jimmylegs » Wed Nov 23, 2011 5:49 pm

found one more tidbit (still just rats, booo)..

Magnesium sulphate reverses the carotid vasoconstriction caused by endothelin-I...
http://ukpmc.ac.uk/abstract/MED/8403787 ... 8751A372A2
"Magnesium sulphate (MgSO4) has been used for many years in the prevention of eclamptic seizures, but its mechanism of action has never been elucidated. Recent studies suggest that cerebral vasospasm is an important feature of eclampsia and we have developed and tested the hypothesis that MgSO4 can reverse cerebral vasoconstriction.
Studies were performed in conscious, male Long Evans rats with pulsed Doppler probes sutured around both common carotid arteries after the external carotid artery had been ligated on the left, thus allowing simultaneous measurement of changes in common and internal carotid blood flow. Intravascular catheters were placed in the abdominal aorta for measurement of systemic blood pressure and in the right jugular vein for administration of drugs. Mean arterial blood pressure and mean Doppler shift signals were used to calculate percentage changes in common and internal carotid vascular conductance.
After a period of recovery the animals were infused with endothelin-1, angiotensin II, neuropeptide-Y or NG-nitro-L-arginine methyl ester alone or in combination, and MgSO4 in low or high dose was infused when the effects of the vasoconstrictors had become established.
MgSO4 itself, at the low dose, had no effect on carotid vascular conductance. Endothelin-1, angiotensin II and neuropeptide-Y all reduced common and internal carotid vascular conductance and this effect was significantly attenuated by low dose MgSO4. The carotid vasoconstrictor action of endothelin-1 was completely abolished by high dose MgSO4."
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Re:

Postby cheerleader » Wed Nov 23, 2011 5:58 pm

Agree, Frodo....more research into this is essential. ET-1 levels are higher in pwMS. Why? As Jimmy suggests, a magnesium deficiency may be part of the reason/solution. But endothelial dysfunction (as indicated by raised ET-1 levels) can be increased by many factors, including low vitamin D, low vitamin B12, eating saturated fats, stress and cortisol, smoking, viruses, bacteria, ischemia and venous hypertension.

Raised ET-1 level in MS-
OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients.

MATERIALS AND METHODS: A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects.

RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.

http://www.ncbi.nlm.nih.gov/pubmed/11315981

ET-1 levels are also higher in Rheumatic Mitral Stenosis-these researchers posit that it is due to increased venous pressure.

Conclusion: Increased production of ET-1 in the pulmonary circulation in response to increased pulmonary artery pressure was not the mechanism of increased circulating ET-1 concentration in patients with MS. We proposed that one of the mechanisms of increased ET-1 concentration in the femoral vein was increased peripheral ET-1 release due to increased systemic venous pressure and mechanical damage of the endothelium.

http://chestjournal.chestpubs.org/conte ... 0.abstract

ET-1 levels are higher after ischemic stroke and myocardial infarction-

Enhanced levels of ET-1, either produced locally or derived from the systemic circulation, within and at the boundaries of the area of cerebral ischemia may there- fore be deleterious to the already-injured neuronal tissue. This situation is similar to that in myocardial infarction, in which elevated plasma ET-1 levels have been reported.7'15 Mainly, ET-1 may cause constriction of collateral vessels and contribute to a vicious circle, with further reduction in regional blood flow, enhance-ment of the severity and size of the infarcted tissue, and worsening of the neurological outcome. If such a sequence of events proves valid, the development of pharmacological strategies to modify the production and activity of this potent vasoconstrictor peptide may be beneficial in improving the outcome of brain ischemia.

http://stroke.ahajournals.org/content/2 ... 4.full.pdf
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby jimmylegs » Wed Nov 23, 2011 6:17 pm

it's true there are a whole constellation of nutrients that affect our health whether we are ms patients or otherwise. however, magnesium deserves a look, especially when it comes to a bioabsorbable stent! :)

magnesium has direct links to hypertension, stress and cortisol, and ischemia.

meanwhile, low vitamin D3 is a definite problem of its own, with potential connections to zinc, which would be low in smokers due to the cadmium issue, and you'd expect to see low zinc in those who are more susceptible to viruses and bacteria. haven't seen anything specific re b12 at first glance.

if i find more studies of nutrient depletion and associated elevation of endothelin-1 levels and/or links to vascular change and/or collagen, i'll add them here :)
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Re: Re:

Postby Cece » Thu Nov 24, 2011 8:42 pm

frodo wrote:
OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients.

MATERIALS AND METHODS: A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects.

RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.



224% higher? and nobody has ever wondered why? and they still tell us the autoimmune theory as a proven fact? each time I read news like this one I feel depressed

I wish there would have been some follow-up research on this. It's a fairly small study. Maybe in a larger one we would have seen some correlation between ET-1 and the different forms, stages of MS or duration of disease? Or maybe not. I did not know, until reading what jimmylegs posted, that magnesium might be effective at bringing down ET-1 levels.

Mainly, ET-1 may cause constriction of collateral vessels and contribute to a vicious circle, with further reduction in regional blood flow, enhance-ment of the severity and size of the infarcted tissue, and worsening of the neurological outcome.

A vicious cycle. Great....
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Re: Connective Tissue Disorders, Collagen and CCSVI

Postby jimmylegs » Sat Nov 26, 2011 7:01 am

anyone have full text access to this study? i'm interested in the magnesium and endothelin-1 levels of all groups before and after:

Effect of magnesium sulfate on plasma endothelin-1 levels in normal and preeclamptic pregnancies.
http://www.ncbi.nlm.nih.gov/pubmed/1471664

i have a sneaking suspicion that magnesium levels would be lower in eclampsia and pre-eclampsia, therefore the endothelin-1 higher. so, treatment with magnesium would then have a more significant effect than in a normal pregnancy, with magnesium levels (possibly) already sufficient, and potentially also lower endothelin-1 to start with.

also, an interesting study. would be nice if there had been a conclusion of some kind in the abstract:

Action of magnesium sulfate in the treatment of preeclampsia-eclampsia
Stroke. 1989;20:1273-1275
http://stroke.ahajournals.org/content/20/9/1273
Abstract
Recent evidence supports the concept that cerebral vasospasm is involved in the pathogenesis of eclampsia. Magnesium, which has a beneficial effect in eclampsia, may act by opposing calcium-dependent arterial constriction, thereby relieving vasospasm. Magnesium may also antagonize the increase in intracellular calcium concentration caused by ischemia and thus prevent cell damage and death. Magnesium might have a role in the treatment of cerebral vasospasm and ischemia, such as occurs in subarachnoid hemorrhage, ischemic stroke, and brain trauma.
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