Vascular health

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Postby gibbledygook » Fri Oct 24, 2008 5:28 am

horsechestnut seems to have arrested my left leg tingles:
1: Biol Pharm Bull. 1997 Oct;20(10):1092-5.Links
Effects of escins Ia, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals.Matsuda H, Li Y, Murakami T, Ninomiya K, Yamahara J, Yoshikawa M.
Kyoto Pharmaceutical University, Japan.

We investigated the effects of escins Ia, Ib, and IIb isolated from horse chestnut, the seeds of Aesculus hippocastanum L., and desacylescins I and II obtained by alkaline hydrolysis of escins on acute inflammation in animals (p.o.). Escins Ia, Ib, IIa, and IIb (50-200 mg/kg) inhibited the increase of vascular permeability induced by both acetic acid in mice and histamine in rats. Escins Ib, IIa, and IIb (50-200 mg/kg) also inhibited that induced by serotonin in rats, but escin Ia didn't. Escins Ia, Ib, IIa, and IIb (200 mg/kg) inhibited the hind paw edema induced by carrageenin at the first phase in rats. Escin Ia (200 mg/kg) and escins Ib, IIa, and IIb (50-200 mg/kg) inhibited the scratching behavior induced by compound 48/80 in mice, but escin Ia was weakest. Desacylescins I and II (200 mg/kg) showed no effect. With regard to the relationship between their chemical structures and activities, the acyl groups in escins were essential. Escins Ib, IIa, and IIb with either the 21-angeloyl group or the 2'-O-xylopyranosyl moiety showed more potent activities than escin Ia which had both the 21-tigloyl group and the 2'-O-glucopyranosyl moiety.

PMID: 9353571 [PubMed - indexed for MEDLINE]
link

1: Eur J Pharmacol. 1996 Nov 14;315(2):227-33. Links
Effect of aescine on hypoxia-induced activation of human endothelial cells.Arnould T, Janssens D, Michiels C, Remacle J.
Laboratoire de Biochimie Cellulaire, Facultés Universitaires Notre dame de la Paix, Namur, Belgium.

Phlebotonic drugs are very often old drugs which improve symptoms in chronic venous insufficiency but their precise mechanism remains unclear. One reason for this lack of information is our poor understanding of the aetiology of the varicose vein. One hypothesis which is being more and more substantiated is that the origin of the disease lies in the activation of the endothelium during blood stasis, leading to a cascade of reactions which, in the long term, alter the structure of the vein wall. In this work, we tested aescine (Reparil i.v. form), a phlebotonic drug, in an in vitro model which mimics this situation, i.e. human endothelial cells exposed to hypoxic conditions. Aescine was shown to inhibit 2 important steps of the activation of endothelial cells incubated 120 min under hypoxia the decrease in ATP content, which is the starting point of the activation cascade, and the increase in the activity of phospholipase A2, an enzyme responsible for the release of precursors of inflammatory mediators. Hypoxia-activated endothelial cells also increase their adhesiveness for neutrophils. This process could also be prevented in a dose-dependent manner if endothelial cells were incubated in the presence of aescine. This inhibition was confirmed by morphological observations in scanning electron microscopy. All 3 effects were already evidenced at 100 ng/ml and were maximal at 750 ng/ml. These effects obtained at very low concentrations probably represent one of the main molecular and cellular mechanisms that underlie, among others, protection of the vessel wall. Objective criteria for our understanding of the preventive action of this phlebotonic drug are, thus, provided.

PMID: 8960888 [PubMed - indexed for MEDLINE]
link

1: Arzneimittelforschung. 1994 Jan;44(1):25-35.Links
Veinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extract.Guillaume M, Padioleau F.
Lipha Group, Department of Pharmacology, Suresnes, France.

Horse chestnut extract (HCE), containing 70% escin, is the main active component of Veinotonyl 75. The aim of this work was to investigate pharmacological properties attempting to elucidate the efficacy of HCE in chronic venous insufficiency. Veinotonic and lymphagogue properties: HCE dose dependently contracts the canine saphenous isolated vein (cumulative doses 5 x 10(-8) to 5 x 10(-4) g/ml). Its action lasts more than 5 h. In the perfused canine saphenous vein, HCE (25-50 mg in bolus) increases the venous pressure of the normal vein and the pathological vein stenosed 8 days before, and the contractile response to noradrenaline is significantly potentiated. Moreover, during the perfusion in inverse direction of the blood stream, a clear contracting effect on the valves is also obtained with HCE. In the anaesthetized dog, HCE in situ improves the femoral vein compliance and opposes the venous distension obtained during clamping in a carotido-femoral perfusion with constant flow. In other respects, HCE significantly increases femoral venous pressure and flow, together with thoracic lymphatic flow, while respecting the arterial parameters (2.5 and 5 mg/kg i.v.). Vasculotropic action: HCE dose dependently diminishes the cutaneous capillary hyperpermeability induced either by injections of phlogistic agents as histamine and serotonin in the rat (100 to 400 mg/kg p.o.), or by an irritative agent (chloroform) application in the rabbit (50 to 300 mg/kg p.o. and 2.5 to 5 mg/kg i.v.). It significantly increases the vascular resistance in the guinea pig fed a scorbutigenic diet as measured by the petechia method (50 to 400 mg/kg p.o.). Antiedema and antiinflammatory properties: HCE decreases the formation of edemas induced in the rat's hind paw, one of lymphatic origin, the other of inflammatory origin (200 to 400 mg/kg p.o.). In an experimental model of pleurisy in the rat HCE suppresses plasmatic extravasation and leucocytes emigration into the pleural cavity (200 to 400 mg/kg p.o.; 1 to 10 mg/kg i.v.). It decreases the connective tissue formation in the subchronic model of inflammatory granuloma in the rat (400 mg/kg p.o. and 5-10 mg/kg s.c.). Antiradical mechanism of action both in vitro and in vivo: HCE dose dependently inhibits both enzymatic and non-enzymatic in vitro lipid peroxidation (5 x 10(-6) to 5 x 10(-4) g/ml).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID: 8135874 [PubMed - indexed for MEDLINE]
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3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Postby rainer » Sat Oct 25, 2008 4:24 pm

More blood in the brain evidence.

http://www.nationalmssociety.org/news/n ... px?nid=410

Progressive MS and KLK enzymes (Dr. Scarisbrick’s team): Understanding the processes that lead to tissue damage in MS is crucial to feed parallel efforts to protect and repair the brain and spinal cord. Dr. Scarisbrick previously found elevated levels of “KLK6” (a newly identified member of the kallikrein enzyme family) in areas of damage found in tissue samples from people with MS. Now, in a follow-up study, the group has studied the levels of KLK6 and other kallikreins in blood samples taken from 35 people with different clinical courses of MS and 62 controls without MS.

The results show that KLK1 and KLK6 were elevated in people with MS, with the highest levels appearing in people with secondary-progressive MS (a course of MS that initially is relapsing-remitting and then becomes progressive, with or without occasional relapses and minor remissions).

The team also exposed nerve cells isolated from mice to KLK1 or KLK6 in the laboratory, and found that the enzymes promoted nerve cell loss. Dr. Scarisbrick is continuing to study the role of these enzymes in nerve fiber injury and hopes to find a way to target them with therapeutic strategies for people with progressive MS.





Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage

http://www.springerlink.com/content/nlc29hm7k3q474bv/

Abstract

Aims/hypothesis. Kallikrein-binding protein (KBP) is a serine proteinase inhibitor (serpin). It specifically binds to tissue kallikrein and inhibits kallikrein activity. Our study was designed to test its effects on retinal neovascularization and vascular permeability.

Methods. Endothelial cell proliferation was determined by [3H] thymidine incorporation assay and apoptosis quantified by Annexin V staining and flow cytometry. Effect on retinal neovascularization was determined by fluorescein angiography and count of pre-retinal vascular cells in an oxygen-induced retinopathy (OIR) model. Vascular permeability was assayed by the Evans blue method. Vascular endothelial growth factor (VEGF) was measured by Western blot analysis and ELISA.

Results. Kallikrein-binding protein specifically inhibited proliferation and induced apoptosis in retinal capillary endothelial cells. Intravitreal injection of KBP inhibited retinal neovascularization in an OIR model. Moreover, KBP decreased vascular leakage in the retina, iris and choroid in rats with OIR. Blockade of kinin receptors by specific antagonists showed significantly weaker inhibition of endothelial cells, when compared to that of KBP, suggesting that the anti-angiogenic activity of KBP is not through inhibiting kallikrein activity or kinin production. KBP competed with 125I-VEGF for binding to endothelial cells and down-regulated VEGF production in endothelial cells and in the retina of the OIR rat model.

Conclusion/interpretation. Kallikrein-binding protein is a multi-functional serpin, and its vascular activities are independent of its interactions with the kallikrein-kinin system. Inhibition of VEGF binding to its receptors and down-regulation of VEGF expression could represent a mechanism for the vascular activities of KBP.
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Postby cheerleader » Sat Oct 25, 2008 5:23 pm

Terry wrote:Cheer,

Good reading! Thanks so much.
I will use it as reference.
and btw, I have NEVER finished a sudoku puzzle.
Thanks for your help.

Terry


Glad you got it, Terry. Hope it helps. Dim's bounced back as spam, so I'll try to hook up that web server thing this week. Yeah, sudoko seems to suit my OCD tendancies :? I think the gang's onto something with vascular/endothelium health.
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby DIM » Sat Oct 25, 2008 11:56 pm

Sorry Cheer forgot to tell you our e-mail server blocks all .exe, .zip, .rar files!
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Postby Wonderfulworld » Sun Oct 26, 2008 1:56 pm

Do people feel that thinner or thicker blood is a good thing? Or is it neither, and just endothelial walls need strengthening?

My own feeling for a long time is in agreement with a lot of this thread. I have always bruised too easily. When MS symtoms really kicked off with me I had numbness and a sluggish feeling in my circulation. I took aspirin at that time and every time I did that, the deadness, the circulation problems seemed to ease.

I have been tested extensively for Hughes syndrome, for all the clotting disorders m- all negative apart from protein s deficiency but that was probably taken too close to a pregnancy and was a false positive. With 3 miscarriages under my belt I was given baby-aspirin and progesterone for my last pregnancy and now I am lucky to have a very healthy baby boy.

Recently noticed the bruising again, and the dead arms and legs and it happened during a relapse.
Currently taking multi-vits, milk thistle, naudicelle evening primrose oil, vitamin d drops, high dose vit c. I think I might add horse chestnut having seen this information.
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Postby cheerleader » Sun Oct 26, 2008 3:15 pm

Wonderfulworld wrote:Do people feel that thinner or thicker blood is a good thing? Or is it neither, and just endothelial walls need strengthening?


Hey WW...
The endothelium is just one layer of flat cells, but it's in charge of so many things. It's not only a lining to the blood vessels, it's a signaling organism. Read up on endothelium derived relaxing factor (EDRF) discovered to be nitric oxide by Nobel winning scientists in 1998. Nitric oxide is secreted by the endothelium, and if it is thrown out of balance, alot of things can go awry. In some people it's hardening of arteries, in others it's diabetes, in others clotting disorders or the BBB is compromised and lesions are formed. Not coincidently, MS lesions have a proliferation of NO in them. I think NO must be out of whack before a relapse, which would explain why circulation is affected and blood is thickened (both mediated by NO)

I believe oxidative stress is one of the culprits. So many things in our modern lifestyles create oxidative stress. Everything you're doing supplement-wise should help this. I'm so glad you were able to have a baby boy..I can't believe my baby boy is 5'9" and still growing. :)
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby gibbledygook » Mon Oct 27, 2008 1:52 am

Wonderworld, I think you should start with ginkgo biloba and salvia then try the horsechestnut. I think the endothelium in MS is highly constricted and that the ginkgo and salvia dilate and relax the vessels and that this is the most important. I am still experimenting with this all but I can clearly see and feel and notice improvements with small doses of ginkgo combined with salvia. By that I mean about 960mg of ginkgo and about 4.8g of salvia (this herb is very good for my bowel function), the ginkgo less so. I haven't yet established what the right dose for horsechestnut is.
gg 8)
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Postby Wonderfulworld » Mon Oct 27, 2008 5:04 am

Thanks AC. That explains a lot. Nitric Oxide is related to uric acid too see: http://content.onlinejacc.org/cgi/conte ... /38/7/1850 - uric acid being one of my "pets"!

Yes I am just thrilled with my son - he is 8 months now, sturdy bolshie little divil :lol: Today is a "waaaahhhhh" day every time I try to put him down, or get him to play, but I think he is finding his character - at the expense of my sanity :lol: Ahh no, I truly enjoy every day, even the display of character type of days - I'd imagine there will be lots of them to come too!

Gibbledygook - unfortunately I can't tolerate ginkgo - I come out in a raw rash every time I take it. Do you think it would be a problem just to take the horsechestnut?
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Postby gibbledygook » Mon Oct 27, 2008 5:45 am

I also developed a rash on high dose ginkgo. I just don't know at this stage what is what except that salvia and ginkgo are helping me walk and control my bladder and bowel. I tried horsechestnut in high dose (11grams!) a few days ago and initially thought it was great but after a night of alcohol (oops, getting married so got to have some liquor) my leg felt quite stiff again. But the dose was way too high I'm sure.

I would foremost recommend a vasodilator like gingko. How about quercetin? This is a component of ginkgo and reduces PECAM and is a vasodilator. However I would also try horsechestnut is you haven't had any luck with quercetin/ginkgo/salvia. This is all wonderfully exciting experimentation but I'm nearly 100% convinced that I'm on the right track with this.

Also gotu kola:
1: Angiology. 2001 Oct;52 Suppl 2:S49-54.Links
Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model.Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Bavera P, Bucci M, Ippolito E.
Irvine Vascular Laboratory, St Mary's Hospital and Imperial College, London, UK.

Fifty patients with diabetic microangiopathy were studied by laser Doppler flowmetry (measuring skin blood flow at rest) (RF) and the venoarteriolar response (VAR), by transcutaneous PO2 and PCO2 measurements, and by capillary permeability evaluation (rate of ankle swelling [RAS]). Thirty of these patients were treated for 6 months with total triterpenic fraction of Centella asiatica (TTFCA) (60 mg twice daily), a drug active on microcirculation and capillary permeability. A control group of ten patients was treated with placebo and another group of ten patients was left without treatment thus acting as a second control group. After six months there were no significant changes in the two control groups. There was a significant improvement of microcirculatory parameter in patients treated with TTFCA. RF (abnormally increased at the beginning of the treatment) decreased, and the VAR (impaired at the beginning of the study) improved. PO2 increased and PCO2 decreased the abnormally increased capillary permeability was also improved (decreased). According to these data, TTFCA is useful in diabetic microangiopathy by improving microcirculation and decreasing capillary permeability. Also TTFCA protects against the deterioration of microcirculation due to diabetic microangiopathy.

PMID: 11666124 [PubMed - indexed for MEDLINE]
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3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Postby DIM » Mon Oct 27, 2008 1:40 pm

[quote="Wonderfulworld"]Thanks AC. That explains a lot. Nitric Oxide is related to uric acid too see: http://content.onlinejacc.org/cgi/conte ... /38/7/1850 - uric acid being one of my "pets"![quote]
Interesting article, according to it uric acid may be bad for MSers although we all know from previous researches that it helps a lot, what to believe?
I give to my wife 1gr inosine/day in order to increase her low uric acid levels and the above article makes me wonder...
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Postby cheerleader » Mon Oct 27, 2008 2:08 pm

Dmitris-
Inosine/uric acid is contraindicated for cardiovascular disease, since uric acid levels tend to be high in CVD. Uric acid is a peroxynitrite (toxic free radical) scavenger and has been shown to be helpful for MSers, who typically have low uric acid levels-
http://www.ncbi.nlm.nih.gov/pubmed/16202511

Elevated uric acid relates to gout, metabolic syndrome, obesity and cardiovascular disease. If you're really concerned, you can test your wife's uric acid levels - Jeff's are normal on 1g daily.
It seems the balance of nitric oxide has alot to do with disease!
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby DIM » Tue Oct 28, 2008 12:29 am

Thanks Cheer, I do know about the connection of high uric acid levels and gout but wonder how it is good for MS and simultaneously works against vascular health.
How I understand it the key word here is "balance", am I wrong?
That's why pycnogenol a powerful blood thinner helps a lot as it promotes vascular health and contrary to what someone conclude it reduces BBB permeability!
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Postby gibbledygook » Tue Oct 28, 2008 4:21 am

I think that the vasodilatory herbs/supplements are the ones to focus on not least because people with MS have so much endothelin 1, a potent vasoconstrictor. Certainly my experience of a combination of ginkgo and salvia is that these are helpful.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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Postby Wonderfulworld » Tue Oct 28, 2008 2:39 pm

10 years ago I was friendly with a medical researcher and he was so interested in what I told him about the whole NO/UA/other weird blips (!!) in MS research he passed on the email of a vascular specialist. I emailed him but he probably thought I was a nut, I never heard back anything.
Think you are all onto something with this though.

Sorry edited to add - I have only seen Salvia in relation to "legal highs" in Ireland - presumably people are smoking it! I don't think you can legally get it as a supplement here. What dosage are you on GG?
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Postby rainer » Tue Oct 28, 2008 4:22 pm

More food for thought: the recent breakthrough regarding Macular Degeneration involves inhibiting vascular endothelial growth factor (VEGF), which promotes forming new blood vessels and encourages them to leak all over our heads. I suspect/hope some of the advancements in this area will benefit MS.

Some relevant links:

Lpath Initiates Dosing in Phase 1 Trial for AMD - mentions M.S. as a promising target :roll: shoot it into my head and I will let you know about that promise :roll:

Bevacizumab (Avastin, Genentech/Roche) is a monoclonal antibody against vascular endothelial growth factor (VEGF). It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels (angiogenesis). Bevacizumab was the first clinically available angiogenesis inhibitor in the United States.

Robo4 Gene – ‘Major Breakthrough” for Eye Diseases : “Many diseases are caused by injury or inflammation destabilizing blood vessels and causing them to leak fluid into adjacent tissues as well. We found a natural pathway – the Robo4 pathway – that counterattacks this by stabilizing blood vessels. Robo4 tells the vessels not to grow, to stabilize, not to explore. The blood vessels have an instruction system that tells them to do the opposite, to stabilize,” study senior author Dr. Dean Li of the University of Utah School of Medicine in Salt Lake City said, according to the Telegraph.co.uk.


Retinal venous sheathing in optic neuritis. Its significance for the pathogenesis of multiple sclerosis.

A systematic study of the frequency of retinal vascular abnormalities and cells in the media has been made in 50 patients presenting with acute optic neuritis. Abnormalities were found in 14 (fluorescein leakage in 10, perivenous sheathing in 6, cells in the vitreous in 6 and in the anterior chamber in 4; in 2 the cells in the media were seen without vascular changes). After a mean follow up of 3.5 years multiple sclerosis (MS) had developed in 8/14 patients with vascular abnormalities and/or evidence of inflammation and in 5/32 without; the difference is significant (P less than 0.02). The occurrence of perivenular abnormalities in a region free of myelin and oligodendrocytes provides evidence that the vascular changes in MS can occur independently of contiguous demyelination, and may be the primary event in the formation of a new lesion.

Inevitably when I go googling for answers, I always find some study like that was done in 1987 that makes me want to walk into the next AAN meeting with a bullhorn and read it aloud.
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