blood vessel pathology suggested in sepsis

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

blood vessel pathology suggested in sepsis

Postby Frank » Sat Jun 25, 2011 12:45 am

Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Postby Cece » Sat Jun 25, 2011 9:08 am

So leaky blood vessels can do a lot of damage....

This was interesting too in the same context:
www.sciencedaily.com/releases/2009/03/090310120347.htm
Through gene and protein analyses in both septic mice and humans, scientists found that cases of severe sepsis featured a unique attribute: the genes within platelets were triggered to produce a protein known as granzyme B, which has been shown in previous studies to contribute to cell death as part of the body's immune response to cancer and viruses. During sepsis, platelets collect within major organs including the spleen, an important infection-fighting organ. As they collect and come into contact with the organ's cells, the granzyme B, if present, will cause the organ's cells to die. Previous research has shown that that this factor may be a major contributor to organ failure. Granzyme B was only detected in humans and mice with the most severe sepsis.

"Detection of granzyme B in platelets could be a huge step forward in battling sepsis," said Dr. Freishtat. "First, as a prognostic indicator, the protein's presence could show more aggressive treatments are needed right off the bat. Eventually, perhaps this knowledge will help us find a way to prevent organ failure by targeting interventions directly at the platelets and granzyme B production."

Presumably if our BBB is leaky and an immune response is taking place, platelets are getting across into our brains too; do they have granzyme B in them?
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Postby cheerleader » Sat Jun 25, 2011 9:47 am

Thanks for this article, Frank. Endothelial dysfunction is a problem in a host of diseases. There is no "cure" for this permeability of vessel lining, but there are ways to boost nitric oxide bioavailability and strengthen the endothelial cells---but these take time and might not be fast enough to prevent systemic sepsis. Our friend just lost his healthy, 40 year old sister to a staph infection. She was in the hospital for a minor procedure, got staph, and her organs shut down....just terrible. We've got to figure this one out.


Here's another abstract from earlier in the year-
http://www.ncbi.nlm.nih.gov/pubmed/21196278
Endothelial activation and dysfunction play a key role in the pathogenesis of sepsis. During septic shock, endothelial dysfunction is involved in microcirculation impairment and organ dysfunction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have several potentially important effects on endothelial function and are implicated in physiological regulation and disease pathophysiology. The imbalance between the production of ROS and their effective removal by non-enzymatic and enzymatic antioxidants systems could induce endothelial dysfunction with alterations of vascular tone, increases in cell adhesion properties (leukocytes and platelet adhesion), increase in vascular wall permeability and a pro-coagulant state. Increasing evidence supports the idea that the principal cause of EC dysfunction during sepsis is cell injury. ROS and RNS contribute to mitochondrial dysfunction by a range of mechanisms and induce both necrotic and apoptotic cell death. Understanding the mechanisms underlying the generation of ROS and RNS in endothelial cells and the causes of endothelial dysfunction in sepsis may help provide therapeutic strategies to tackle endothelial dysfunction and microcirculatory failure in sepsis.
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trial

Postby 1eye » Sat Jun 25, 2011 11:00 am

Opening statements:

The Case for the Prosecution -

Ladies and gentlemen of the jury, it was acknowledged at long last, at the end of the last century, that the bacterium known as Helicobacter pylori, which from now on we will call H. pylori, is the reason behind the common disease of stomach ulcer. The men who discovered it, and its role in gastritis and peptic ulcer disease, Barry Marshall and Robin Warren, were jointly awarded the 1995 Nobel Prize in Physiology or Medicine, by the Nobel Assembly at Karolinska Institutet. Thanks to their pioneering discovery, it is no longer a chronic, frequently disabling condition, but a disease that can be permanently cured.

Here in this courtroom, I intend to prove to all of you, ladies and gentlemen of the jury, that the same bacterium is responsible for the disease previously known as M.S. I intend to give you evidence that will show you that this despicable gram-negative, spiral-shaped bacterium, that we already know colonizes the human gastric epithelium, and is the cause of chronic gastritis, peptic ulceration, and gastric carcinoma, is also guilty of the extra-gastric initiation and progression of other diseases, and in particular the one we are all the most interested in, Chronic Cerebro-Spinal Venous Insufficiency, also known as CCSVI.

The evidence I will show you is complex and compelling.

Exhibit A.

Release of NO by the endothelium induces vasodilation, and therefore reduction of it results in impairment of this function. Depending on where this takes place, several adverse effects occur as a result.

In a study which compared the in vitro effect of H. pylori with unconditioned controls and with controls conditioned with E. coli bacteria, researchers observed the significant effects of H. pylori-secreted factors on some vascular endothelial dysfunction markers. They saw the the significant, greater than 50% reduction in endothelial nitric oxide (NO) on bovine aortic endothelial cells.

Exhibit B.

In the same study just mentioned, researchers noted that the reduction of nitric oxide production by the endothelium caused by H. pylori was remediable by two mechanisms. One of these used S-nitroso-N-acetylpenicillamine, an NO donor. The other remedial mechanism the researchers tried was the atheroprotective impact of laminar shear stress. Laminar shear stress is the dragging frictional force created by blood flow. This model of atheroprotection has been studied extensively elsewhere, also, and is widely recognized. In this study shear was seen to have the expected protection against H. pylori.

Exhibit C.

Lower doses of the H. pylori in the study were seen to be sub-toxic. Reduced oxygenation due to increased contraction and reduced dilation promote angiogenesis. Larger dose response reduces angiogenesis. The result is the pattern of remission followed by chronic progression with no remission.





The Case for the Defense -

In 2003, a group of 90 Polish subjects with "multiple sclerosis" was tested for the antibodies against H pylori. They were found in 17 patients (18.9%), which is markedly lower than that infection rate in Poland. So H pylori infection is not the cause of "MS".

It may be said that this bacterium is very good at avoiding detection, and that the non-detection of antibodies is not conclusive enough of anything. Unjustified aspersions may even be cast on the quality of this study.

It is not necessary to prove that this bacterium is not the cause of CCSVI as long as there is a reasonable doubt that is has been responsible for it. The case for the prosecution leaves such a reasonable doubt. The fact that the cause of CCSVI is unknown, combined that the cause of "MS" is also unknown, is no justification for a finding of guilt against H. pylori. The golden thread that runs through all our justice, is the principle of presumption of innocence. We cannot presume because of the colour of one's skin, or the spiral of one's shape, that one is guilty. Bacteria, like anyone else, must have their guilt proven in a court of law. That is something I think you will find it impossible to do.
"Try - Just A Little Bit Harder" - Janis Joplin
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'MS' is over - if you want it
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trial again

Postby 1eye » Sat Jun 25, 2011 4:15 pm

Helicobacter pylori-induced inhibition of vascular endothelial cell functions: a role for VacA-dependent nitric oxide reduction
Nicholas P. Tobin,Gary T. Henehan,Ronan P. Murphy,John C. Atherton,Anthony F. Guinan,Steven W. Kerrigan,Dermot Cox,Paul A. Cahill,Philip M. Cummins
School of Biotechnology, Dublin City University;School of Food Science and Environmental Health, Dublin Institute of Technology;Wolfson Digestive Diseases Centre, University Hospital Nottingham; Molecular and Cellular Therapeutics, Royal College of Surgeons of Ireland, Dublin, Ireland
Submitted 7 March 2008; accepted in final form 23 July 2008
Am J Physiol Heart Circ Physiol 295: H1403–H1413, 2008.
First published July 25, 2008; doi:10.1152/ajpheart.00240.2008.

Arterioscler Thromb Vasc Biol. 1998 May;18(5):677-85.
Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force.
Traub O, Berk BC.

Science 21 May 1993:
Vol. 260 no. 5111 pp. 1124-1127
DOI: 10.1126/science.7684161
Mechanotransduction across the cell surface and through the cytoskeleton
N Wang, JP Butler, DE Ingber

Neurol Neurochir Pol. 2003 Jan-Feb;37(1):45-8.
[Prevalence of Helicobacter pylori infection among patients with multiple sclerosis].


comments?
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Postby 1eye » Sat Jun 25, 2011 8:16 pm

"Epidemiological and clinical studies provide compelling support for
a causal relationship between Helicobacter pylori infection and en-
dothelial dysfunction, leading to vascular diseases."

"Various mechanisms have been proposed to account for
the contribution of H. pylori to vascular diseases. Molecular
mimicry, oxidative modifications, bacterium-platelet interac-
tions, and even direct plaque modification, leading to endothe-
lial dysfunction or inflammation, have been proposed (12, 26,
43). With respect to plaque modification, perhaps the most
persuasive single piece of evidence supporting this role was the
identification of H. pylori DNA in atherosclerotic plaques. This
finding was key in pointing to the direct involvement of the
bacterium in this specific pathology (1, 2, 17, 36)."

----

"Vac+HPCM BAECs {bovine aortic endothelial cells induced by H.
pylori-conditioned medium (HPCM) prepared from H. pylori 60190
[vacuolating cytotoxin A (Vac+)]} were treated with either
unconditioned media, HPCM (0–25% vol/vol), or Escherichia coli..."

"Vac+HPCM significantly decreased BAEC proliferation, tube formation,
and migration (by up to 44%, 65%, and 28%, respectively)."

This demonstrates the higher dosage's reduction of angiogenesis.

----

"Posttreatment, we also observed sporadic zonnula occludens-1 immunolocal-
ization along the cell-cell border, and increased BAEC permeability to
FD40 Dextran, indicating barrier reduction. These effects were
blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid (VacA in-
hibitor) and were not observed with conditioned media prepared from
either VacA-deleted H. pylori or E. coli."

"As seen
earlier, ZO-1 immunoreactivity along the cell-cell border be-
came highly discontinuous and jagged in response to Vac+
HPCM, consistent with the disruption of intercellular tight
junction integrity... Again, neither Vac- HPCM nor E. coli-
conditioned media had any significant effects."

Thus this pathogen can attack the Blood-Brain-Barrier.

----

"Vac+ HPCM (but not Vac-) reduced nitric oxide (NO) by >50%."

This significantly reduces the ability of smooth muscle to relax.


-anybody interested?
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Postby cheerleader » Sat Jun 25, 2011 8:38 pm

Hi one eye...
Agreed, H pylori is a culprit, indeed! Thanks for the papers.
But H pylori is but one of many, many pathogens that creates endothelial dysfunction. Cpn, bartonella, EBV, and a slew of others can all do the same thing.

The problem is in trying to isolate and make a case for one particular environmental factor for endothelial dysfunction....because cortisol, saturated fats, low vitamin D, smoking, and heavy metals all do the same thing. Anything that disrupts nitric oxide can make this mess. And that's why it's been so hard for MS researchers to locate "the" cause. One week it's EBV, the next it's shingles, then it's stress or smoking. We need to step back and see the forest from the trees...
cheer
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Postby Johnson » Sat Jun 25, 2011 10:10 pm

cheerleader wrote:---redacted---

One week it's EBV, the next it's shingles, then it's stress or smoking. We need to step back and see the forest from the trees...
cheer


That is a very lucid point, which I was just elucidating to my wife. I said that if "anyone" ever figures out the cause of "MS", it will be this forum. Collectively.

There are so many trees in the forest.

There is a constellation of exacerbators.

There is a galaxy of manifestations.

And my thanks too, 1eye. (Can I call you 1i?)
My name is not really Johnson. MSed up since 1993
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Postby 1eye » Sat Jun 25, 2011 10:37 pm

Thank you. I just thought it was interesting that

a) it can disrupt the blood-brain-barrier
b) it can explain remissions which finally stop happening
c) it can cause hypoxia
d) it reduces the smooth muscle tone with a huge reduction
in available energy due to >50% reduced
endothelial production of nitric oxide
e) exercise reduces its negative effect by increasing shear
stress

That's all.
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Postby Shannon » Sun Jun 26, 2011 12:59 am

My comment would be these two points:

1) I suspect that my H. Pylori infection came from my husband, who already had a history of gastric ulcers before I married him, and subsequently I developed "MS" shortly after we were married.

2) Once I was suspected to have bleeding ulcers, from overuse use of NSAIDS to counteract side effects of Avonex, I had an endoscopy to confirm. They also did a biopsy of the stomach lining to test specifically for H. Pylori and the result was negative. When I went back several months later with the same issues, they took blood. This time, to their surprise, I tested positive for H. Pylori antibodies.

So, the timing would seem to have been right for this to have been a cause, but then again, I have been on a roller coaster of "cause du jour" many times before, as Cheerleader has pointed out. Also, I would corroborate with the comment made by (1eye?) that this bacterium is a master at hiding from detection. After all, it is the only non-beneficial kind of bacteria that has ever been able to escape certain death from the highly acidic environment of the human stomach for decades before a prize had to be handed out for it's captor! So elusive in fact, that it took the guy infecting himself on purpose just to prove that it was even there at all.

I implore anyone who has monstrous gas and bad smelling breath, despite doing everyhting possible to avoid it, to be tested and treated. It takes only a simply prescription for something called a "Prev-Pack," which is basically Prevacid and some strong antibiotics to be taken routinely until the pack is gone. Then, it is thought to be gone from your life forever. A simple breath test by your doctor can then confirm this further, though I never needed any proof.

It is thought to be passed from person-to-person mainly from kissing, as it has been found in dental tooth enamel as well. Obviously, it can be spread from drinking after someone with it as well, but not thought to be as common as from kissing. This is why if one spouse tests positive, the other spouse gets the Prev-Pack automatically, no testing needed. Just FYI!
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ccsvi

Postby blossom » Sun Jun 26, 2011 1:12 pm

for whatever it's worth. my x-husbands wife had ms. 20 yrs. later that's what they say i have. i was very very healthy-had a terrible fall-about a week later symptoms started. i know that my spine is playing a big part in my symptoms. but i have even asked the dr.'s if it was possible that since the theory of ms was virus at that time if my x could be a carrier of something that laid dormanent in my body and the stress of the fall activated it.

there is no ms generations back on either side of my family. his family he had first cousin with ms.

maybe they should be checking out connections like this and isolating "if there" is a way- the viruses and bacteria in him. this could be a coincidence but i wonder.

i would gladly have donated his "body parts" to science while we were going through the divorce.
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Postby 1eye » Sun Jun 26, 2011 1:49 pm

I am curious about this pathogen, and about your story. Would you say your progression stopped when it was treated? Or was that already the case? If it reduces the endothelium's ability to produce NO, getting rid of it should reduce loss of muscle tone, fatigue, and heat sensitivity. If it caused permanent damage to the endothelium, I guess this would not come back, but since this is fast-growing tissue, that might take a long time to happen, if it ever does.

Same with smooth muscle tissue. I understood the stomach lining is the fastest growing tissue in the body.

Heat sensitivity still intrigues me. I accept that it is connected to vessels expanding (caused by NO, BTW), but also wonder if heat speeds up some of the reactions that the pathogen produces. It would certainly be interesting to see what effect temperature has on NO in live subjects somehow.
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Postby 1eye » Sun Jun 26, 2011 1:56 pm

i would gladly have donated his "body parts" to science while we were going through the divorce.

Sounds pretty diabolical. I presume you were going to arrange for him to be dead first? :D
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ccsvi

Postby blossom » Sun Jun 26, 2011 4:18 pm

well 1eye, after him dragging me through court for over 8 yrs. and his other actions and me having a total hysterectomy "crazy" plus ms---actually dead or alive would have been ok with me.
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Postby Shannon » Sun Jun 26, 2011 4:43 pm

I would not characterize being treated as having gone into MS remission, or anything like that 1eye. I had relief from gastric troubles, but that was about all. Then again, my memory is so bad! One thing that perplexes me is how my head gets so incredibly hot sometimes, that even my kids touch me and ask if I have a fever. It just seems to be excessive head heat. :( I am so frightened of having strokes as I grow old, as a result of CCSVI/MS.

I think I will have psoriasis though, as my maternal grandmother did in her later years. I have the genetic alteration that puts me at higher risk for that, and even now I have trouble controlling dandruff and itching. I periodically pour rubbing alcohol over my entire scalp for relief from it. My grandmother just ised the creams and treatments from the doctor, but never took anything more than an aspirin, orally.
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