Gibbledygook's anti-viral log

Tell us what you are using to treat your MS-- and how you are doing.

alpha lipoic acid test

Postby gibbledygook » Thu Sep 18, 2008 3:14 am

Well, today I tried 1.2g of solgar alpha lipoic acid, unfortunately on an empty stomach. This made me feel rather unwell so this obviously must be taken on a full stomach. So far this has not improved my leg at all which feels rather stiff this morning. I shall try to take another 800mg at lunch and 1g this pm and see if there is any reaction.

16:00, since taking now 2g of alpha lipoic my walking has been quite difficult and I have felt very tired. However this also feels a bit like when I started a high dose of ashgawandha; a sponginess in the right foot. On the other hand the tingling is very subdued but then again it has been for the last few weeks. The feeling of tiredness/fatigue from which I haven't generally suffered is also odd and was immediately noticeable when I felt sick this morning. It may also have to do with the credit crisis induced lack of sleep. The alarm rings at 5am and we generally watch bloomberg till 1am to see who's next. However I am so far not overly enamoured of alpha lipoic but still it's only the first day and I shall persevere for a few more to see if this much acclaimed supplement can cut the mustard in relatively high dose. I have found Anecdote's recommended site for cheap alpha lipoic - it's called Vitacost.
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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Salvia does what alpha lipoic does (but more cheaply!)

Postby gibbledygook » Fri Sep 19, 2008 12:28 am

Well maybe I've been inhibiting ICAM and VCAM enough with the salvia as here's evidence it does what lipoic acid also does from research above:
1: Carcinogenesis. 2008 Jun 26. [Epub ahead of print] Links
Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion molecules.Nizamutdinova IT, Lee GW, Lee JS, Cho MK, Son KH, Jeon SJ, Kang SS, Kim YS, Lee JH, Seo HG, Chang KC, Kim HJ.
Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.

The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-alpha-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 siRNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of VEGF and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anti-cancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.

PMID: 18586687 [PubMed - as supplied by publisher]
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This may explain why I definitely noticed an effect on the 3g of alpha lipoic but that in the right motor dysfunction leg it was negative. Think I will reduce the alpha lipoic to 600mg 3 times daily and see what happens then. 8)


Looks like panax ginseng also inhibits ICAM and VCAM:
1: Int J Cardiol. 2008 Aug 29;128(3):350-8. Epub 2007 Aug 13. Links
Effects of four medicinal herbs on human vascular endothelial cells in culture.Ling S, Nheu L, Dai A, Guo Z, Komesaroff P.
Department of Medicine, Monash University Central and Eastern Clinical School, Prahran, Melbourne, Victoria, Australia. shanhong.ling@med.monash.edu.au

BACKGROUND: Danshen (DS, Salvia miltiorrhiza), Shanchi (SQ, Panax notoginseng), Shanzai (SZ, Hawthorn) and Heshouwu (HSW, Polygonum multiflorum Thunb) are four medicinal herbs commonly used in traditional Chinese medicine and previously shown to have activity that may contribute to cardiovascular protection. This study aims to investigate effects of these herbs on vascular endothelial cells with respect to cell viability and expression of cellular adhesion molecules under inflammatory conditions. METHODS: Herbal extracts were prepared by an established industrial manufacturing process. Human umbilical vein endothelial cells (HUVEC) were incubated with the herbal extract under normal or serum-free culture and tumor necrosis factor (TNF) alpha stimulation. Cell apoptosis, apoptosis-associated gene expression, expression of cellular adhesion molecules, DNA synthesis, and growth were assessed via morphological examination, Annexin-V staining, Western blotting analysis, Flow-Cytometry, [(3)H]-thymidine incorporation assay, and cell number study. RESULTS: SZ and HSW significantly inhibited apoptosis in HUVEC undergoing serum deprivation and TNFalpha stimulation, accompanied by down-regulation of caspase-3 gene expression. DS and SQ significantly attenuated TNFalpha-induced expression of adhesion molecule VCAM-1 and also ICAM-1 by DS in the cells. All four herbs at therapeutic concentrations (100 microg/mL) inhibited DNA synthesis (10-42% decrease in [(3)H]-thymidine incorporation rates) and growth (5-10% decrease in cell numbers) in HUVEC under normal cultures. CONCLUSION: DS, SQ, SZ and HSW are physiologically active on human vascular endothelial cells. The actions by HSW and SZ to reduce apoptosis and DS and SQ to inhibit adhesion molecule expression may help protect endothelial function and inhibit atherogenesis, while their actions to inhibit DNA synthesis and cell growth may weaken the ability of endothelial repair. Further studies are needed to identify the chemical compounds responsible to these physiological effects by these herbs.

PMID: 17692965 [PubMed - in process]
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But here it looks as though salvia increases ICAM in monocytes (above is endothelial cells):
1: Int J Cardiol. 2005 Oct 20;105(1):40-5. Links

Comment in:
Int J Cardiol. 2006 Nov 18;113(3):437-8.
Chinese herbs Danshen and Gegen modulate key early atherogenic events in vitro.Sieveking DP, Woo KS, Fung KP, Lundman P, Nakhla S, Celermajer DS.
Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, NSW 2050, Australia. d.sieveking@hri.org.au

Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, we investigated the effect of a preparation of these herbs on two key processes in the early stages of atherosclerosis; macrophage lipid loading and monocyte adhesion to endothelial cells. Human monocyte derived macrophages (HMDMs) were treated with 0.1-1.0 mg/ml of the herbal mixture in aqueous buffers and loaded with acetylated LDL (AcLDL) (50 microg/ml) for 72 h, and analyzed for cholesterol (C) and cholesteryl esters (CE), via HPLC. Human endothelial cell monolayers were also treated with 0.1-1.0 mg/ml of the herbal mixture and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were assessed via ELISA. Compared to control conditions, the herbal mixture induced a significant dose-related decrease in the total cholesterol (free and esterified) in the HMDMs (p<0.001 by ANOVA). By contrast, the herbs also induced an increase in ICAM-1 expression (p<0.001) and monocyte adhesion at higher concentrations (p<0.05). In conclusion, treatment of cells with this preparation of Danshen and Gegen, a commonly used Chinese health supplement, results in a dose-related suppression of AcLDL uptake by human macrophages, and an increase in the level of ICAM-1 expression and adhesion of monocytes to endothelial cells. These herbs therefore show the ability to modulate key early events in atherosclerosis.

PMID: 16207543 [PubMed - indexed for MEDLINE]
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Here again it is inhibiting ICAM and VCAM in endothelial cells but not elsewhere:
1: Clin Exp Pharmacol Physiol. 2005 Jul;32(7):571-8. Links
Effects of a Chinese herbal preparation on vascular cells in culture: mechanisms of cardiovascular protection.Ling S, Dai A, Guo Z, Yan X, Komesaroff PA.
Department of Medicine, Central and Eastern Clinical School, Monash University, Prahran, Victoria, Australia.

1. The use of traditional Chinese medicinal herbs or their pharmaceutical products for disease prevention and management is becoming increasingly popular in Western countries. Mixtures of various Chinese herbs have been used for the treatment of syndromes clinically overlapping Western cardiovascular syndromes. One modern preparation, known as the 'Cardiotonic Pill' (CP), is a pharmaceutical product derived mainly from a medicinal herb, Salvia miltiorrhiza bunge, and recently widely used in Chinese hospitals for the prevention and management of ischaemic cardiovascular diseases. Although the CP is believed to confer an extensive range of benefits, little is known about the physiological actions of this medicine, particularly at the cellular and molecular levels. Therefore, the aim of the present study was to explore possible cellular mechanisms of the CP on the cardiovascular system. 2. Cultured human vascular endothelial cells (EC) and vascular smooth muscle cells (VSMC) were exposed to the CP at various concentrations for periods ranging from hours to days. Cellular DNA synthesis was determined by a [(3)H]-thymidine incorporation assay, proliferation and death were assessed by investigations of cell numbers and apoptosis, whereas the expression of extracellular adhesion molecules was analysed by flow-cytometry and Western blotting. 3. The CP extract at concentrations of less than 200 microg/mL was not associated with cell damage. At doses beyond the therapeutic range (10-20 microg/mL), the CP appeared to exert a mild inhibitory effect on DNA synthesis and proliferation of EC in serum-enriched cultures. The CP significantly attenuated tumour necrosis factor-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in a dose-dependent manner, with 50 and 100 microg/mL CP producing decreases in the expression of ICAM-1 of 26-32% and 32-44%, respectively, and of VCAM-1 of approximately 23% and 27-42%, respectively. The CP did not affect apoptosis in EC under conditions of serum-deprivation. 4. In VSMC, the CP significantly inhibited platelet-derived growth factor BB-induced DNA synthesis and cell proliferation in a dose-dependent manner. The CP did not affect VSMC expression of adhesion molecules. 5. We conclude that the CP inhibits expression of ICAM-1 and VCAM-1 in EC and proliferation of VSMC in a manner that has potentially beneficial therapeutic effects.

PMID: 16026517 [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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soluble ICAM high in relapse

Postby gibbledygook » Mon Sep 22, 2008 9:31 am

the soluble form of ICAM is higher during relapse:
1: J Neurol. 2005 Feb;252(2):146-50. Links
Intrathecal sICAM-1 production in multiple sclerosis--correlation with triple dose Gd-DTPA MRI enhancement and IgG index.Acar G, Idiman F, Kirkali G, Ozakbaş S, Oktay G, Cakmakçi H, Idiman E.
Karşiyaka Neurology Outpatient Clinic, Dokuz Eylül University, Izmir, Turkey. goksemind@yahoo.com

In this study the aim was to evaluate the intrathecal sICAM-1 production in multiple sclerosis (MS) patients during relapse and remission. In addition to this, we assessed whether there is a correlation between intrathecal sICAM-1 production and other disease activity markers such as IgG index and gadolinium enhancement in magnetic resonance imaging (MRI). Twenty four relapsing-remitting MS patients were included in the study. Serum and cerebrospinal fluid (CSF) samples were obtained both during relapse and remission. The soluble form of ICAM (sICAM) was measured by the ELISA method in serum and CSF. Cranial MRI with triple dose gadolinium injection was performed for each patient both during relapse and remission. Serum levels of sICAM-1 (245.23 +/- 92.88 ng/ml) were higher during relapse than those in remission (219.90 +/- 110.94 ng/ml), but the difference was not statistically significant. In relapse periods CSF levels of sICAM-1 (1.304 +/- 0.92 ng/ml) were higher than those in remission (1.06 +/- 0.86 ng/ml), but this was not significant. However, during relapse periods patients had significantly higher sICAM-1 index values (1.76 +/- 0.60) than those found during remission periods (1.01 +/- 0.44) (p < 0.05). The IgG index values were higher in relapse periods than in remission (0.88 +/- 0.37 vs. 0.67 +/- 0.28) (p < 0.005). On T1 weighted images following triple dose Gd injection, at least two or more enhancing lesions were present in 22/24 of the patients (91%) in relapse and 4/24 of the patients (19%) in remission. There was strong correlation both between the sICAM-1 index and Gd enhancement (r =0 .72 p < 0.05) and sICAM-1 index and IgG index in relapse (r = 0.69 p < 0.05). In conclusion, there is association between high sICAM-1 and IgG indices, as well as between high sICAM-1 index and Gd enhancing MRI lesions in relapsing MS patients.

PMID: 15729518 [PubMed - indexed for MEDLINE]
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I have been experimenting with different levels and now brands of alpha lipoic acid. The solgar 200mg seem much stronger than the Lambers 250mg! I'm now taking about 3g a day of the Lamberts which is at least cheaper. I'm still suffering from increased fatigue and seem to spend much of my day yawning. This has been since trialling the alpha lipoic. Mmm.

1: J Neuroimmunol. 2005 Jan;158(1-2):222-30. Links
Expression of adhesion molecules on peripheral lymphocytes predicts future lesion development in MS.Eikelenboom MJ, Killestein J, Izeboud T, Kalkers NF, Baars PA, van Lier RA, Barkhof F, Uitdehaag BM, Polman CH.
Department of Neurology, VU University Medical Center, P.O. Box 7057, Amsterdam 1007, The Netherlands. j.eikelenboom@vumc.nl

The expression of adhesion molecules (alpha4beta1-integrin, LFA-1, ICAM-1) on T cells, measured by flow cytometry, was compared in different subtypes of multiple sclerosis (MS) and related to future lesion development as seen as delta T1 and T2 lesion load per year on magnetic resonance imaging (MRI). LFA-1 and alpha4beta1-integrin showed higher expression on CD4 and CD8 T lymphocytes in the secondary progressive compared to the relapsing-remitting (CD4: p<0.01, p=ns, p<0.05; CD8: p<0.001, p<0.001, p<0.001, respectively) and primary progressive MS phase (CD4: p<0.001, p<0.01, p<0.05; CD8: p<0.01, p<0.01, p<0.001, respectively). The adhesion molecule expression of alpha4- (r=0.31; p<0.05) and beta1-integrin (r=0.38; p<0.01) on CD4+ cells and of LFA-1beta on both CD4+ and CD8+ (r=0.28, p<0.05) and r=0.29; p<0.05, respectively) cells was significantly related to increase in T2 lesion load. Our study provides further evidence for the involvement of integrins in lesion development, shown as T2 lesions on MRI in MS.

PMID: 15589057 [PubMed - indexed for MEDLINE]
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maybe we should try this herb:
1: Planta Med. 1998 Dec;64(8):683-5.Links
Cistifolin, an integrin-dependent cell adhesion blocker from the anti-rheumatic herbal drug, gravel root (rhizome of Eupatorium purpureum).Habtemariam S.
Department of Physiology and Pharmacology, University of Strathclyde, U.K.

During routine screening of medicinal plants for small molecular weight inhibitors of cell adhesion, the crude ethanolic extract of the anti-rheumatic herbal drug gravel root (rhizome of Eupatorium purpureum), was identified as a potent inhibitor of some beta 1 and beta 2 integrin-mediated cell adhesions. The active principle of gravel root has now been isolated and identified as 5-acetyl-6-hydroxy-2,3-dihydro-cis-2-isopropenyl-3- tiglinoyloxybenzofuran (1). Compound 1 inhibited integrin-dependent cell-cell and cell-protein interactions in vitro with EC50 values between 7-20 micrograms/ml. As with indomethacin, 1 administered orally two hours before induction of inflammation (in rat paw) by carrageenan inhibited oedema formation in a dose (10 and 50 mg/kg)-dependent manner. It appears that 1 has therapeutic potential for diseases where integrin adhesion molecules play a significant role.

PMID: 10075543 [PubMed - indexed for MEDLINE]

Related ArticlesAntiinflammatory activity of the antirheumatic herbal drug, gravel root (Eupatorium purpureum): further biological activities and constituents. [Phytother Res. 2001] Angiotensin II enhances integrin and alpha-actinin expression in adult rat cardiac fibroblasts. [Hypertension. 2000] Cell adhesion and migration properties of beta 2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation. [J Biol Chem. 2001] Activation of protein kinase C by phorbol esters modulates alpha2beta1 integrin on MCF-7 breast cancer cells. [Exp Cell Res. 1999] Evaluation of anti-inflammatory potential of Bergenia ciliata Sternb. rhizome extract in rats. [J Pharm Pharmacol. 2001] » See all Related Articles...
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or cetirizine:
1: Int Immunopharmacol. 2004 Mar;4(3):349-53. Links
Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders.Namazi MR.
Dermatology Department, Shiraz University of Medical Sciences, P.O. Box 71955-687 Shiraz, Iran. namazi_mr@yahoo.com

Type 1, or cellular, immune response is characterized by overproduction of TNF-alpha, IFN-gamma, IL-1, IL-2 and IL-8 and is the underlying immune mechanism of psoriasis, alopecia areata, rheumatoid arthritis, Crohn's disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis (EAU). Type 2 immune response is seen in antibody-mediated autoimmune diseases. Based on the pharmacokinetic effects of cetirizine and allopurinol, this paper introduces these two safe and inexpensive drugs as novel potential agents against cell-mediated autoimmune disorders. Cetirizine, supposed to inhibit DNA binding activity of NF-kappa B, inhibits the expression of adhesion molecules on immunocytes and endothelial cells and the production of IL-8 and LTB4, two potent chemoattractants, by immune cells. It induces the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages and reduces the number of tryptase positive mast cells in inflammation sites. Tryptase is a chemoattractant, generates kinins from kininogen, activates mast cells, triggers maturation of dendritic cells and stimulates the release of IL-8 from endothelial cells and the production of Th1 lymphokines by mononuclear immunocytes. Allopurinol is a free radical scavenger, suppresses the production of TNF-alpha and downregulates the expression of ICAM-1 and P2X(7) receptors on monocyte/macrophages. ICAM-1 serves as a ligand for LFA-1 (on T lymphocytes), allowing proper antigen presentation. P2X(7) receptors are thought to be involved in IL-1beta release, mitogenic stimulation of T lymphocytes and the probable cytoplasmic communication between macrophages and lymphocytes at inflammation sites. Allopurinol was markedly more effective than prednisolone in treating experimental autoimmune uveitis and in combination with cyclosporine suppressed the inflammatory reaction of this condition more effectively than either agent alone. As allopurinol is a competitive inhibitor of xanthine oxidase and decreases serum levels of uric acid, which is protective against multiple sclerosis, it should preferably be coadministered with uric acid precursors in the treatment of this condition. Cetirizine and allopurinol may prove of benefit in the treatment of various cellular autoimmune disorders.

PMID: 15037212 [PubMed - indexed for MEDLINE]
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However I have necked loads of cetirizine for my hayfever and it hasn't assisted either my hayfever or my MS so I won't be bothering to experiment with that one.

Genetic marker for ICAM 1 increases ms susceptibility:
1: Hum Immunol. 2003 Mar;64(3):345-9. Links
Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis.Nejentsev S, Laaksonen M, Tienari PJ, Fernandez O, Cordell H, Ruutiainen J, Wikström J, Pastinen T, Kuokkanen S, Hillert J, Ilonen J.
Department of Virology, University of Turku, Finland. serneje@gene.cimr.cam.ac.uk

Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenesis of multiple sclerosis (MS), whereas sequence variations in the ICAM-1 gene could potentially be responsible for the genetic susceptibility to MS. We studied an association of MS with the 13,848A>G (K469E) polymorphism of the ICAM-1 gene in Finnish and Spanish cases and controls and affected families. An increased risk for the AA (Lys(469)/Lys(469)) genotype was found in both populations. The effect observed was found to be strongest among the HLA-DQB1*0602-positive subjects, which implies genetic heterogeneity of MS. Meta-analysis of all published datasets supports increased risk of MS for the ICAM-1 Lys(469) homozygotes (relative risk = 1.3, p = 0.002).

PMID: 12590979 [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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VEGF

Postby gibbledygook » Tue Sep 23, 2008 11:25 am

VEGF is upregulated in MS and may increase vascular permeability:
1: Life Sci. 2008 Sep 12;83(11-12):404-12. Epub 2008 Jul 30. Links
Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats.Zhu CS, Hu XQ, Xiong ZJ, Lu ZQ, Zhou GY, Wang DJ.
Department of Neurology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, People's Republic of China.

Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease. However, it remains unknown whether anti-VEGF modalities could serve as a potential treatment for such central nervous system (CNS) autoimmune diseases. We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3) (the first three extracellular domains of Flt-1, the hVEGF receptor-1). Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF-induced inflammatory cell infiltration in matrigel plugs. When given intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector significantly reduced disease severity compared to untreated rats. sFlt-1(1-3) gene transfer blocked VEGF and greatly reduced the number of cells that express VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.

PMID: 18721816 [PubMed - in process]
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flavonoids inhibit vascular permeability/angiogenesis:
1: Pharmacol Res. 2008 Apr;57(4):259-65. Epub 2008 Feb 23. Links
Antiangiogenic effects of flavonoids and chalcones.Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L.
Department of Pharmacology, Faculty of Medicine, P.J. Safarik University, Trieda SNP 1, 04011 Kosice, Slovak Republic. jan.mojzis@upjs.sk

Angiogenesis, the development of new blood vessels from the existing vasculature, is essential in normal developmental processes. Uncontrolled angiogenesis is a major contributor to a number of disease states such as inflammatory disorders, obesity, asthma, diabetes, cirrhosis, multiple sclerosis, endometriosis, AIDS, bacterial infections and autoimmune disease. It is also considered a key step in tumour growth, invasion, and metastasis. Angiogenesis is required for proper nourishment and removal of metabolic wastes from tumour sites. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds are recently tested for their antiangiogenic potential. Among the most frequently studied are polyphenols present in fruits and vegetables. Plant polyphenols inhibit angiogenesis and metastasis through regulation of multiple signalling pathways. Specifically, flavonoids and chalcones regulate expression of VEGF, matrix metalloproteinases (MMPs), EGFR and inhibit NFkappaB, PI3-K/Akt, ERK1/2 signalling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of flavonoids and chalcones and examines underlying mechanisms.

PMID: 18387817 [PubMed - indexed for MEDLINE]
link

1: J Clin Immunol. 2007 May;27(3):246-56. Epub 2007 Mar 6. Links
Vascular endothelial growth factor (VEGF) in autoimmune diseases.Carvalho JF, Blank M, Shoenfeld Y.
Rheumatology Division, São Paulo University, School of Medicine, São Paulo, Brazil.

Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field.

PMID: 17340192 [PubMed - indexed for MEDLINE]
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1: Front Biosci. 2007 Jan 1;12:1615-28.Links
Corticotropin-releasing hormone and the blood-brain-barrier.Theoharides TC, Konstantinidou AD.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA. theoharis.theoharides@tufts.edu

Increased blood-brain-barrier (BBB) permeability precedes any clinical or pathologic signs and is critical in the pathogenesis of multiple sclerosis (MS) and brain metastases. CD4+ TH1 cells mediate demyelination in MS, but how they get sensitized and enter the brain to induce brain inflammation remains obscure. TH2 cytokines associated with allergic disorders have recently been implicated in MS, while genes upregulated in MS plaques include the mast cell-specific tryptase, the IgE receptor (Fc-epsilon-RI) and the histamine-1 receptor. Mast cell specific tryptase is elevated in the CSF of MS patients, induces microvascular leakage and stimulates protease-activated receptors (PAR), leading to widespread inflammation. BBB permeability, MS and brain metastases appear to worsen in response to acute stress that leads to the local release of corticotropin-releasing hormone (CRH), which activates brain mast cells to selectively release IL-6, IL-8 and vascular endothelial growth factor (VEGF). Acute stress increases BBB permeability that is dependent on CRH and mast cells. Acute stress shortens the time of onset of experimental alleric encephalomyelitis (EAE) that does not develop in W/W mast cell deficient or CRH -/- mice. Brain mast cell inhibition and CRHR antagonists offer novel therapeutic possibilities.

PMID: 17127408 [PubMed - indexed for MEDLINE]
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1: J Immunol. 2006 Oct 15;177(8):5574-84. Links
IL-1beta regulates blood-brain barrier permeability via reactivation of the hypoxia-angiogenesis program.Argaw AT, Zhang Y, Snyder BJ, Zhao ML, Kopp N, Lee SC, Raine CS, Brosnan CF, John GR.
Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai School of Medicine, New York, NY 10029, USA.

Loss of blood-brain barrier (BBB) integrity is believed to be an early and significant event in lesion pathogenesis in the inflammatory demyelinating disease multiple sclerosis (MS), and understanding mechanisms involved may lead to novel therapeutic avenues for this disorder. Well-differentiated endothelium forms the basis of the BBB, while astrocytes control the balance between barrier stability and permeability via production of factors that restrict or promote vessel plasticity. In this study, we report that the proinflammatory cytokine IL-1beta, which is prominently expressed in active MS lesions, causes a shift in the expression of these factors to favor plasticity and permeability. The transcription factor, hypoxia inducible factor-1 (HIF-1), plays a significant role in this switch. Using a microarray-based approach, we found that in human astrocytes, IL-1beta induced the expression of genes favoring vessel plasticity, including HIF-1alpha and its target, vascular endothelial growth factor-A (VEGF-A). Demonstrating relevance to MS, we showed that HIF-1alpha and VEGF-A were expressed by reactive astrocytes in active MS lesions, while the VEGF receptor VEGFR2/flk-1 localized to endothelium and IL-1 to microglia/macrophages. Suggesting functional significance, we found that expression of IL-1beta in the brain induced astrocytic expression of HIF-1alpha, VEGF-A, and BBB permeability. In addition, we confirmed VEGF-A to be a potent inducer of BBB permeability and angiogenesis, and demonstrated the importance of IL-1beta-induced HIF-1alpha in its regulation. These results suggest that IL-1beta contributes to BBB permeability in MS via reactivation of the HIF-VEGF axis. This pathway may represent a potential therapeutic target to restrict lesion formation.

PMID: 17015745 [PubMed - indexed for MEDLINE]
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This herb looks interesting:
1: Clin Cancer Res. 2004 Dec 15;10(24):8266-74. Links
Pseudolaric acid B inhibits angiogenesis and reduces hypoxia-inducible factor 1alpha by promoting proteasome-mediated degradation.Li MH, Miao ZH, Tan WF, Yue JM, Zhang C, Lin LP, Zhang XW, Ding J.
Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.

PURPOSE: Pseudolaric acid B (PAB), the naturally occurring diterpenoid isolated from the root bark of Pseudolarix kaempferi Gordon tree (Pinaceae), possesses potent antifungal and pregnancy-terminating effects that may be tightly associated with angiogenesis. This study was to examine its angiogenic inhibition, impact on vascular endothelial growth factor (VEGF) secretion from tumor cells and the possible mechanism of action. EXPERIMENTAL DESIGN: Angiogenesis inhibition was assessed by the human umbilical vascular endothelial cell proliferation, migration, and tube-formation assays, as well as the chorioallantoic membrane assay. ELISA, reverse transcription-PCR, and Western blotting analyses were performed to examine VEGF protein secretion, mRNA expression, and the possible mechanism in hypoxic MDA-MB-468 cells. RESULTS: PAB displayed potent in vitro antiangiogenic activity shown by inhibiting VEGF-stimulated proliferation and migration and fetal bovine serum-stimulated tube formation of human umbilical vascular endothelial cells in a concentration-dependent manner. Moreover, PAB (10 nmol per egg) significantly suppressed in vivo angiogenesis in the chorioallantoic membrane assay. On the other hand, PAB abrogated hypoxia-induced VEGF secretion from MDA-MB-468 cells via reducing HIF-1alpha protein. Additional analyses using LY294002 and U0126 indicated that the increase in hypoxia-inducible factor 1 (HIF-1)alpha protein level was highly dependent on phosphatidylinositol 3'-kinase and p42/p44 mitogen-activated protein kinase activities in hypoxic MDA-MB-468 cells. However, PAB treatment did not affect the active (phosphorylated) forms of Akt and Erk. Interestingly, the selective proteasome inhibitor MG-132 completely reversed the reduction of HIF-1alpha protein in the PAB-treated MDA-MB-468 cells. CONCLUSIONS: PAB displays the dual antiangiogenic activities of directly inhibiting endothelial cells and abrogating paracrine stimulation of VEGF from tumor cells due to reducing HIF-1alpha protein by promoting its proteasome-mediated degradation in MDA-MB-468 cells, which has potential clinical relevance.

PMID: 15623602 [PubMed - indexed for MEDLINE]
link

as does hesperidin:
1: Mol Cell Biochem. 2007 Nov;305(1-2):153-61. Epub 2007 Jul 13. Links
Hesperidin inhibits expression of hypoxia inducible factor-1 alpha and inflammatory cytokine production from mast cells.Choi IY, Kim SJ, Jeong HJ, Park SH, Song YS, Lee JH, Kang TH, Park JH, Hwang GS, Lee EJ, Hong SH, Kim HM, Um JY.
College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.

The citrus unshiu peel has been used traditionally as a medicine to improve bronchial and asthmatic conditions or cardiac and blood circulation in Korea, China, and Japan. Here, we report the effects of citrus unshiu peel water extract (CPWE) on the phorbol myristate acetate (PMA)+calcium ionophore A23187-induced hypoxia-inducible factor-1alpha (HIF-1alpha) activation and inflammatory cytokine production from the human mast cell line, HMC-1 cells. We compared CPWE with hesperidin, a common constituent of citrus unshiu. CPWE and hesperidin inhibited the PMA+A23187-induced HIF-1alpha expression and the subsequent production of vascular endothelial growth factor (VEGF). In addition, CPWE suppressed PMA+A23187-induced phosphorylation of the extracellular signal-regulated kinase (ERK). We also show that the increased cytokines interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha level was significantly inhibited by treatment of CPWE or hesperidin. In the present study, we report that CPWE and hesperidin are inhibitors of HIF-1alpha and cytokines on the mast cell-mediated inflammatory responses.

PMID: 17629775 [PubMed - indexed for MEDLINE]
link

or dang gui:
1: Pathobiology. 2006;73(3):141-8. Links
Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma.Lee WH, Jin JS, Tsai WC, Chen YT, Chang WL, Yao CW, Sheu LF, Chen A.
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

OBJECTIVE: Previous studies have demonstrated the utility of the traditional Chinese herb danggui in the treatment of chronic myelogenous leukemia. Our aim was to examine whether it might similarly be used to treat glioblastoma multiforme. METHODS: The lipid-soluble active ingredients of danggui were extracted with acetone (AS-AC) or chlorophenol (AS-CH) and their antiproliferative and proapoptotic effects were studiedin vitro on cultured GBM 8401 cells and in vivoon tumors in nude mice. RESULTS: After a 24-hour treatment, either AS-AC or AS-CH at a lower (50 micro g/ml) and a higher concentration (100 micro g/ml) significantly inhibited the proliferative activity of GBM 8401 cultured cells by 30-50%, as well as the expression of cathepsin B and vascular endothelial growth factor (VEGF). In nude mice, the growth of the tumor was inhibited by 30% by AS-CH or AS-AC (20 mg/kg; p < 0.05) and by 60% by AS-CH or AS-AC (60 mg/kg; p < 0.05). AS-AC and AS-CH also significantly inhibited microvessel formation in the tumors of nude mice. CONCLUSIONS: Danggui may inhibit tumor growth by reducing the level of VEGF and the proapoptotic protein, cathepsin B. Thus, danggui may be useful in the treatment of high-grade astrocytomas.

PMID: 17085958 [PubMed - indexed for MEDLINE]
link

And finally gool old gingko biloba:
1: Acta Pharmacol Sin. 2004 Oct;25(10):1306-11.Links
Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro.Qiu Y, Rui YC, Li TJ, Zhang L, Yao PY.
Department of Pharmacology, School of Pharmacy, Second Medical Military University, Shanghai 200433, China.

AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases. Copyright 2004 Acta Pharmacologica Sinica

PMID: 15456532 [PubMed - indexed for MEDLINE
link

and finally finally good old salvia:
1: J Nat Prod. 2007 Jul;70(7):1093-7. Epub 2007 Jun 21. Links
Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1.Dat NT, Jin X, Lee JH, Lee D, Hong YS, Lee K, Kim YH, Lee JJ.
Molecular Cancer Research Center, Korean Research Institute of Biosciences and Biotechnology, Daejeon 305-333, Korea.

The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the adaptation and proliferation of tumor cells; therefore HIF-1 has become an important target in the development of anticancer drugs. A phytochemical study of the CHCl3-soluble fraction of Salvia miltiorrhiza, which strongly inhibited hypoxia-induced reporter gene expression, led to the isolation of 12 abietane-type diterpenes. Of these compounds, sibiriquinone A (1), sibiriquinone B (2), cryptotanshinone (3), and dihydrotanshinone I (4) potently inhibited hypoxia-induced luciferase expression with IC50 values of 0.34, 3.36, 1.58, and 2.05 microM on AGS cells, a human gastric cancer cell line, and 0.28, 3.18, 1.36, and 2.29 microM on Hep3B cells, a human hepatocarcinoma cell line, respectively. Consistently, 1 and 4 dose-dependently suppressed the HIF-1alpha accumulation and 1 inhibited mRNA expression of vascular endothelial growth factor (VEGF) under hypoxia. These results suggest that the anticancer activity of tanshinones is likely at least in part associated with their inhibition of HIF-1 accumulation.

PMID: 17583950 [PubMed - indexed for MEDLINE]
link

oops. forgot rhubarb root:
1: Int J Cancer. 2006 Jun 1;118(11):2711-20. Links
Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation.Kwak HJ, Park MJ, Park CM, Moon SI, Yoo DH, Lee HC, Lee SH, Kim MS, Lee HW, Shin WS, Park IC, Rhee CH, Hong SI.
Laboratory of Functional Genomics, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)-A-induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose-dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF-A. Emodin also inhibits basic fibroblast growth factor-induced proliferation and migration of HUVECs and VEGF-A-induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase-2 and VEGF-A-stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF-A receptor-2 (KDR/Flk-1) and downstream effector molecules, including focal adhesion kinase, extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF-A-induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF-A-induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk-1 and downstream effector molecules is a possible underlying mechanism of the anti-angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk-1 may be involved in the inhibitory function of emodin toward VEGF-A-induced angiogenesis in vitro and responsible for its potent anti-angiogenic in vivo.

PMID: 16388516 [PubMed - indexed for MEDLINE]
link

and ganoderma lucidum:

1: Life Sci. 2006 Feb 23;78(13):1457-63. Epub 2005 Nov 2. Links
Ganoderma lucidum polysaccharides peptide inhibits the growth of vascular endothelial cell and the induction of VEGF in human lung cancer cell.Cao QZ, Lin ZB.
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100083, China.

Ganoderma lucidum Polysaccharide Peptide (Gl-PP) has shown some effects as anti-tumors in mice and potential anti-angiogenesis. In this study, we elucidated the possible mechanism of Gl-PP action on anti-angiogenesis of tumor. Our research indicated that the proliferation of HUVECs was inhibited by Gl-PP in a dose-dependent fashion, but not because of cytotoxicity. Flow cytometric studies revealed that Gl-PP treatment of HUVECs could induce cell apoptosis directly. Moreover, addition of Gl-PP also led to a reduction of Bcl-2 anti-apoptotic protein expression and an increase of Bax pro-apoptotic protein expression of HUVECs. Therefore, inducing cell apoptosis by Gl-PP might be the mechanism of inhibiting HUVEC proliferation. Human lung carcinoma cells PG when exposed to high dose of Gl-PP in hypoxia for 18 h resulted in a decrease in the secreted VEGF. Taken together, these findings support the hypothesis that the key attribute of the anti-angiogenic potential of Gl-PP is that it may directly inhibit vascular endothelial cell proliferation or indirectly decrease growth factor expression of tumor cells.

PMID: 16269156 [PubMed - indexed for MEDLINE]
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However I tried ganoderma lucidum in quite high dose during the summer and found my leg stiffer. BUT now that salvia is working so well perhaps it would improve matters. And the alpha lipoic is making my leg stiffer too. Mmm. Have reduced the alpha lipoic to 1.5g today.

Alas all of the vascular endothelial growth factor inhibitors listed above would be bad in pregnancy. So I won't be experimenting for a while. Could dysregulation at the VEGF level be why women suffer disproportionately? We need plenty of VEGF for healthy placental growth and we are hit in our child-bearing years.

Must eat rhubarb:
1: Zhongguo Zhong Yao Za Zhi. 2008 Mar;33(6):672-5.Links
[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale][Article in Chinese]


Tian FS, Li ZB, Wang YS, Su XH, Li WD, Wang XY.
Endocrinology Department, CangZhou Affiliated hospital of integrated TCM-WM, Hebei Medical University, Cangzhou 061001, China. cztianfsh@sian.com

OBJECTIVE: To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. METHOD: After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, RESULT: Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). CONCLUSION: Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

PMID: 18590198 [PubMed - in process]
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Last edited by gibbledygook on Wed Sep 24, 2008 3:45 am, edited 1 time in total.
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Rhubarb root

Postby gibbledygook » Wed Sep 24, 2008 3:40 am

Rheum looks interesting. I wonder if MS inflammation starts in the stomach?
1: Int Immunopharmacol. 2008 Nov;8(11):1481-92. Epub 2008 May 28. Links
The beneficial effect of Rheum tanguticum polysaccharide on protecting against diarrhea, colonic inflammation and ulceration in rats with TNBS-induced colitis: The role of macrophage mannose receptor in inflammation and immune response.Liu L, Guo Z, Lv Z, Sun Y, Cao W, Zhang R, Liu Z, Li C, Cao S, Mei Q.
Department of Pharmacology, School of Pharmacy, Forth Military Medical University, Xian 710032, Shaanxi, PR China.

Rhubarb has been used as a folk remedy for gastrointestinal disease in China for over two thousand years. In the present study, we evaluated the effect of Rheum tanguticum polysaccharide (RTP), a water soluble fraction extracted from rhubarb, on protection from inflammation and colonic damage in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. RTP protected against diarrhea, colon weight increase, and ulceration induced by TNBS. It was at least as effective as dexamethasone (DEX). RTP significantly decreased myeloperoxidase (MPO) activity in the colonic mucosa. Oral administration of RTP was as effective as intraperitoneal (i.p.) injection on toxicity protection and MPO activity. To further investigate the possible underlying mechanism, we studied the role of mannose receptor (MR) in cytokine secretion, ligand binding and endocytosis of macrophages. The secretion of IFN-gamma was dramatically increased while IL-4 decreased in colitis compared to the control (normal rats), and RTP restored the condition similar to the control in vivo. The secretion of IFN-gamma by macrophages was induced by RTP and lipoarabinomannan (LAM) but not mannose in vitro. Mannose completely inhibited the effect of RTP, while RTP and LAM affected each other on IFN-gamma secretion. The MR-mediated ligand binding and endocytosis of macrophages were markedly decreased in colitis and RTP restored their function to near normal condition. The results indicated that RTP targeted MR and down-regulation of Th1-polarized immune response may be the possible mechanism for its attenuation of intestinal inflammation and damage. RTP may be useful for treatment of patients with inflammatory bowel disease.

PMID: 18790466 [PubMed - in process]
link

rhubarb affects the stomach hormones:
1: Zhonghua Shao Shang Za Zhi. 2008 Apr;24(2):111-3.Links
[Effect of rheum on gastrointestinal hormones in rats with severe scald injury][Article in Chinese]


Guo X, Tan MY, Xiong AB, Guo L.
Department of Burns and Plastic Surgery, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.

OBJECTIVE: To observe the changes in motilin (MTL), substance P (SP), vasoactive intestinal peptide (VIP) and somatostatin (SS) in plasma of rats with severe scald injury at early stage and the effect of rheum on their changes. METHODS: Eighty-eight Wistar rats were randomly divided into normal control group (NC, n = 8), scald group (S, gavage of distilled water after full-thickness scald, n = 40), therapeutic group (T, gavage of rheum solution after full-thickness scald, n = 40). The blood samples were harvested from inferior vena cava at 6, 12, 24, 48, 72 post scald hours (PSH) to determine the levels of MTL, SS, SP and VIP with radioimmunoassay. RESULTS: (1) The levels of MTL and SP were (198 +/- 28), (61 +/- 10) ng/L, respectively, in NC group. The levels of MTL and SP in S group reached their minimum values [(110 +/- 15), (30 +/- 5) ng/L, respectively] at 6 PSH, then ascended slowly, peaked at 72 PSH but still lower than those in NC group (P < 0.05). The levels of MTL and SP slowly descended in T group, reached normal levels at 48 PSH, and obviously higher than those in NC group at 72 PSH [(232 +/- 32), (73 +/- 11) ng/ L, respectively, P < 0.05], which were higher than those in S group at 6 -72 PSH. (2) The levels of VIP and SS were (35 +/- 6), (30 +/- 5) ng/L, respectively, in NC group. The levels of VIP and SS in S group were (70 +/- 12), (49 +/- 9) ng/L at 6 PSH, which were obviously higher than those in NC group (P < 0.01), then descended slowly, but still higher than normal level at 72 PSH (P < 0.05). The levels of VIP and SS in T group ascended slowly, reached the normal level at 48 PSH, which were lower than those in S group at each time points, and VIP reached peak value at 12 PSH. CONCLUSION: Rheum may regulate secretion and release of gastrointestinal hormones to plasma in rats with severe scald injury at early stage.

PMID: 18785410 [PubMed - in process]
link

reduces endothelin 1 and icam and vcam (like salvia):
1: Zhongguo Zhong Yao Za Zhi. 2008 Mar;33(6):672-5.Links
[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale][Article in Chinese]


Tian FS, Li ZB, Wang YS, Su XH, Li WD, Wang XY.
Endocrinology Department, CangZhou Affiliated hospital of integrated TCM-WM, Hebei Medical University, Cangzhou 061001, China. cztianfsh@sian.com

OBJECTIVE: To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. METHOD: After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, RESULT: Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). CONCLUSION: Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

PMID: 18590198 [PubMed - in process]
link


best bet diet people often refer to intestinal permeability. This study suggests rhubarb inhibits this.
1: Am J Chin Med. 2007;35(6):929-36. Links
Effects of crude rhubarb on intestinal permeability in septic patients.Fang XL, Fang Q, Luo JJ, Zheng X.
Department of Intensive Care Unit, The First Affiliated Hospital, College of Medical Sciences, Zhejiang University, Hangzhou 31003, China.

The therapeutic effect of crude rhubarb on intestinal permeability was investigated in septic patients. Forty septic patients were enrolled in this study and randomly divided into two groups: the crude rhubarb treatment group (n = 18) and the control group (n = 22). The same treatments were given to both groups except that the crude rhubarb treatment group was administrated with crude rhubarb powders (3 g, tid, p.o). The levels of procalcitonin, D-lactate in plasma and lactulose/mannitol (L/M) ratio in the urine were determined on the first day and the sixth day after treatment with or without crude rhubarb. There were no significant differences in procalcitonin, L/M ratio and D-lactate on the first day between the crude rhubarb treatment group and the control group (p > 0.05). However, the ratio of L/M on the sixth day for the control group was 0.167 +/- 0.036, while that of the crude rhubarb treatment group was 0.062 +/- 0.013 (p < 0.05). Moreover, the levels of procalcitonin and D-lactate in the crude rhubarb treatment group were obviously lower than those in the control group on the sixth day (procalcitonin: 4.11 +/- 1.40 microg/L vs. 2.21 +/- 0.61 mug/L; D-lactate: 0.24 +/- 0.06 ng/L vs. 0.09 +/- 0.03 ng/L, p < 0.05, both). These data confirmed that crude rhubarb's effects on septic patients of ameliorating intestinal permeability.

PMID: 18186579 [PubMed - indexed for MEDLINE]

Related Articles[Effects of raw rhubarb on plasma D-lactate and procalcitonin expressions in patients with sepsis] [Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006] The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]. [Crit Care. 2002] Glutamine and recombinant human growth hormone protect intestinal barrier function following portal hypertension surgery. [World J Gastroenterol. 2007] Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability. [J Pediatr Gastroenterol Nutr. 1997] Intestinal permeability in patients with chemotherapy-induced stomatitis. [J Cancer Res Clin Oncol. 2001] » See all Related Articles...
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great if you have cardio/cholesterol issues:@
1: Am J Chin Med. 2007;35(4):583-95. Links
Treatment with rhubarb improves brachial artery endothelial function in patients with atherosclerosis: a randomized, double-blind, placebo-controlled clinical trial.Liu YF, Yu HM, Zhang C, Yan FF, Liu Y, Zhang Y, Zhang M, Zhao YX.
Medical School, Shandong University, Jinan, China. liuyf@sdu.edu.cn

Rhubarb has been used to decrease plasma cholesterol levels and reduce vascular endothelial cellular damage in recent years. However, it is not known whether reported lipid-lowering effects are associated with the improvement of endothelial function. This work aimed to elucidate the therapeutic effects of rhubarb on serum lipids and brachial artery endothelial function, as well as to investigate the relationship between them. One hundred and three patients with atherosclerosis were randomly divided into two groups: patients in the control and the trial group received a placebo and rhubarb, respectively, in addition to the 6 month baseline therapy. Serum lipids and brachial artery endothelial functions were measured in all patients before and after treatment. A total of 83 patients completed the 6-month follow-up protocol. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the trial group decreased significantly and LDL-C was significantly lower than that in the control group. Flow-mediated dilation (FMD) in the trial group was significantly higher after treatment in comparison to the baseline and to the control group. Improvement in FMD correlated with the decreased magnitude of TC and LDL-C levels. The results obtained appeared to confirm that rhubarb significantly improves endothelial function mainly due to lipid-lowering effects in patients with atherosclerosis.

PMID: 17708625 [PubMed - indexed for MEDLINE]
link

good for peri-menopausal anxiety:
1: Menopause. 2007 Mar-Apr;14(2):270-83. Links

Comment in:
Menopause. 2007 Jul-Aug;14(4):809-10.
The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety and improves health state and general well-being in perimenopausal women.Kaszkin-Bettag M, Ventskovskiy BM, Kravchenko A, Rettenberger R, Richardson A, Heger PW, Heger M.
Health Research Services Ltd., St. Leon-Rot, Germany. marietta.kaszkin@h-r-s.biz

OBJECTIVE: To investigate the efficacy of the special extract ERr 731 from the roots of Rheum rhaponticum compared with placebo on anxiety, health state, and general well-being in perimenopausal women. DESIGN: This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial, in which 109 perimenopausal women with climacteric complaints and anxiety received either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12 weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's Health Questionnaire, and the Psychological General Well-Being Index were used to measure anxiety, health state, and subjective psychological well-being. RESULTS: The results demonstrate that ERr 731 is highly effective in reducing anxiety in perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/-4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731 also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate" or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the double-blind phase, which correlated well with the reduction in number and severity of hot flushes. This was reflected by a high rate of ERr 731 women reporting a marked improvement in health state and general well-being. CONCLUSIONS: ERr 731 is an effective medication for women with menopause-related anxiety and improves their health state and general well-being.

PMID: 17213754 [PubMed - indexed for MEDLINE]
link
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alpha lipoic better in small quantities.

Postby gibbledygook » Wed Sep 24, 2008 4:24 am

Well, today I halved the amount of alpha lipoic to 500mg and now my leg feels much better. Having not noticed anything at the beginning with 600mg I think maybe I have just returned to where I was at the start of the experiment. Doesn't seem like the alpha lipoic adds anything to the salvia.
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Re: alpha lipoic better in small quantities

Postby NHE » Wed Sep 24, 2008 5:04 am

Just a short note, lipoic acid in doses higher than 100 mg can deplete biotin.

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Postby gibbledygook » Wed Sep 24, 2008 5:41 am

Ah. And people with MS have lower levels of biotin:
1: Acta Neurol Scand. 1999 Jun;99(6):387-92.Links
Cerebrospinal fluid levels of biotin in various neurological disorders.Anagnostouli M, Livaniou E, Nyalala JO, Evangelatos G, Zournas C, Ithakissios DS, Papageorgiou C.
Department of Neurology of Medical School, Athens National University, Greece.

OBJECTIVES: To analyse biotin concentrations in human cerebrospinal fluid (CSF) and serum from controls without evidence of nutritional or neurological disorders and patients with common neurological disorders. PATIENTS AND METHODS: Cerebrospinal fluid was obtained from patients by lumbar puncture, serum was prepared from freshly drawn whole blood and biotinidase in samples was inhibited before being analysed for biotin by radioligand assay. RESULTS: Assay characteristics were within an acceptable range (intra-and interassay coefficient of variations were 8.8 and 12.0 respectively, recovery: 91-114% and sensitive, lowest standard concentration 15 ng/l). Significantly lower values for biotin were found in patients with multiple sclerosis (both CSF and serum) in comparison to the controls. Significantly reduced values for cerebrospinal fluid biotin were found in epileptics compared to controls, whereas, in serum the difference was approaching significance. No significant differences were observed in other groups of patients. CONCLUSION: There is a significant reduction in cerebrospinal fluid biotin in epileptics and patients with multiple sclerosis compared to controls. In epileptics this may be related to competition between biotin and anticonvulsants bearing carbamide ring for absorption. Reduction of biotin levels in patients with multiple sclerosis could be attributed to intestinal malabsorption caused by the underlying disease or a biotin-binding immunoglobulin which may be involved in multiple sclerosis pathogenesis.

PMID: 10577274 [PubMed - indexed for MEDLINE]
link

I wonder if that is what's been happening.
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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back on the blood

Postby gibbledygook » Wed Sep 24, 2008 6:42 am

Fibrin is deposited on the damaged axon after bbb leak. Plasminogen activator inhibitor isupregulated and prevents fibrinolysis.
1: Neuropathol Appl Neurobiol. 2008 Apr;34(2):216-30. Epub 2007 Nov 5. Links
Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor-1 knockout mice: the effect of fibrinolysis during neuroinflammation.East E, Gverić D, Baker D, Pryce G, Lijnen HR, Cuzner ML.
Department of Neuroinflammation, Institute of Neurology, University College London, London, UK. E.East@ion.ucl.ac.uk

During neuroinflammation in multiple sclerosis (MS) fibrinogen, not normally present in the brain or spinal cord, enters the central nervous system through a compromised blood-brain barrier. Fibrin deposited on axons is ineffectively removed by tissue plasminogen activator (tPA), a key contributory factor being the upregulation of plasminogen activator inhibitor-1 (PAI-1). Aims: This study investigated the role of PAI-1 during experimental neuroinflammatory disease. Methods: Chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of MS, was induced with spinal cord homogenate in PAI-1 knockout (PAI-1(-/-)) and wild type (WT) mice, backcrossed onto the Biozzi background. Results: Disease incidence and clinical severity were reduced in PAI-1(-/-) mice, with animals developing clinical signs significantly later than WTs. Clinical relapses were absent in PAI-1(-/-) mice and the subsequent reduction in neuroinflammation was coupled with a higher capacity for fibrinolysis in spinal cord samples from PAI-1(-/-) mice, in association with increased tPA activity. Axonal damage was less apparent in PAI-1(-/-) mice than in WTs, implicating fibrin in both inflammatory and degenerative events during CREAE. Conclusions: PAI-1 is a potential target for therapy in neuroinflammatory degenerative diseases, allowing effective fibrin removal and potentially reducing relapse rate and axonal damage.

PMID: 17983428 [PubMed - indexed for MEDLINE]
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Salvia inhibits this:
1: J Cell Biochem. 2005 Sep 1;96(1):109-16. Links
Salvianolic acid B attenuates plasminogen activator inhibitor type 1 production in TNF-alpha treated human umbilical vein endothelial cells.Zhou Z, Liu Y, Miao AD, Wang SQ.
Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.

Plasminogen activator inhibitor type 1 (PAI-1), which plays a role in the development of atherosclerosis, is produced by endothelial cells following stimulation with various inflammatory cytokines such as tumor necrosis factor (TNF-alpha). In the present study, we investigated the effects of a potent water-soluble antioxidant, salvianolic acid B (SalB; derived from the Chinese herb, Salvia miltiorrhiza), on the expression of PAI-1 in TNF-alpha-treated human umbilical vein endothelial cells (HUVECs). We found that SalB inhibited TNF-alpha-induced PAI-1 mRNA production and protein secretion in HUVECs. Treatment with SalB (0.05 and 0.15 microM) notably attenuated TNF-alpha induced expression of PAI-1 to 90.5% and 74.6%, respectively, after 12 h, and to 75.1% and 64.2%, respectively, after 18 h. We also observed a dose-dependent decrease in PAI-1 protein production in the presence of SalB. We then used pathway inhibitors to investigate which step of the TNF-alpha induced signaling pathway was targeted by SalB. We found that the c-Jun N-terminal kinase (JNK) inhibitor, SP600125, increased the inhibitory effects of SalB on TNF-alpha-induced PAI-1 secretion, whereas the nuclear factor-kappaB (NF-kappaB) inhibitor, emodin, and the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, did not. A gel shift assay further showed that SalB inhibited the TNF-alpha-activated NF-kappaB and AP-1 DNA binding activities in a dose-dependent manner. Collectively, these results indicate that the NF-kappaB and ERK-AP-1 pathways are possible targets of SalB in the regulation of TNF-alpha-stimulated PAI-1 production in HUVECs. Copyright 2005 Wiley-Liss, Inc

PMID: 16052513 [PubMed - indexed for MEDLINE]
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astragalus also looks good but I've tried this herb in large dose and I suffered worse spasms:
1: J Vasc Res. 1997 Jul-Aug;34(4):273-80.Links
Regulation of the fibrinolytic potential of cultured human umbilical vein endothelial cells: astragaloside IV downregulates plasminogen activator inhibitor-1 and upregulates tissue-type plasminogen activator expression.Zhang WJ, Wojta J, Binder BR.
Department of Vascular Biology and Thrombosis Research, University of Vienna, Austria.

We have investigated whether the saponin astragaloside IV (AS-IV), a 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol, purified from the Chinese herb drug Astragalus membranaceus, which is used in traditional Chinese medicine to treat cardiovascular diseases, might affect the fibrinolytic potential of cultured human umbilical vein endothelial cells (HUVECs). When HUVECs were conditioned with AS-IV, a dose (0.01-100 microg AS-IV/ml)- and time-dependent decrease in plasminogen activator inhibitor type 1 (PAI-1) and an increase in tissue-type plasminogen activator (t-PA) synthesis were observed, which were significant from 1 microg AS-IV/ml and from 12 h of incubation with 100 microg AS-IV/ml. PAI-1 antigen decreased from 641 +/- 86 to 318 +/- 18 ng/10(5) cells/24 h, whereas t-PA antigen increased from 4.1 +/- 0.3 to 9.7 +/- 0.4 ng/10(5) cells/24 h after addition of 100 microg AS-IV/ml. PAI-1 activity decreased to 30% of control level, whereas t-PA activity and t-PA-PAI-1 complexes reached a maximum stimulation of 3- and 5-fold over control levels, respectively, in the conditioned media of HUVECs treated with 100 microg AS-IV/ml for 24 h. PAI-1-specific mRNA expression decreased to 55% (2.2 kb) and 72% (3.2 kb), 66% (2.2 kb) and 88% (3.2 kb), and 19% (2.2 kb) and 41% (3.2 kb) of control values after incubation for 6, 12 and 18 h, respectively, whereas t-PA-specific mRNA increased 2-, 2.5- and 1.4-fold in HUVECs treated with 100 microg/ml AS-IV for 6, 12, and 18 h, respectively. In conclusion our data give evidence that in fact AS-IV can increase the fibrinolytic potential of cultured HUVECs not only by upregulating the expression of t-PA as NG-R1 does, but also by downregulating the expression of PAI-1.

PMID: 9256087 [PubMed - indexed for MEDLINE]
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MAybe this herb would be better:
1: Planta Med. 2003 Dec;69(12):1109-12.Links
Modulation of PAI-1 and tPA activity and thrombolytic effects of corilagin.Shen ZQ, Dong ZJ, Peng H, Liu JK.
Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, P R China.

In this study, Charlton's and Tomihisa's methods were modified to investigate the thrombolytic effect of corilagin from the Chinese herbal plant Phyllanthus urinaria L., as well as its effect on carotid artery patency status. The activity of type 1 plasminogen activator inhibitor (PAI-1) in rat plasma or platelet-released substances and tissue-type plasminogen activator (tPA) in rat plasma was assayed by use of a chromogenic substrate. The results showed that corilagin had a dose-dependent thrombolytic effect in rats. 5 mg/kg of corilagin produced a nearly similar reperfusion rate to that of 20000 U/kg of urokinase, whereas it produced a lower reocclusion rate than urokinase. Corilagin significantly inhibited PAI-1 activity in rat plasma or platelet-released substances while it elevated plasma tPA activity, in a concentration-dependent manner. Corilagin, however, had no influence on rabbit platelet aggregation. It is indicated that corilagin inhibited PAI-1 activity and increased tPA activity, and this property of corilagin is assumed to be responsible for the thrombolytic effect. Abbreviations. PO:persistent occlusion CR:cyclic reflow PP:persistent patency PAI-1:type 1 plasminogen activator inhibitor tPA:tissue-type plasminogen activator PBS:phosphate buffer solution IC (50):50 % of inhibitory concentration PRP:platelet-rich plasma ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet-activating factor

PMID: 14750026 [PubMed - indexed for MEDLINE]
link
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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IS MS hypertension with cerebrovascular disease?

Postby gibbledygook » Wed Sep 24, 2008 7:16 am

1: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Apr;21(4):257-9.Links
[Clinical observation on effect of intervention therapy with anticoagulant in treating patients of hypertension complicated with acute ischemic cerebrovascular disease][Article in Chinese]


Ma QC, Ma JS, Sun NL.
Department of Hypertension, People's Hospital of Beijing University, Beijing 100044.

OBJECTIVE: To study the changes of blood coagulation-fibrinolysis-C protein system in patients of hypertension with acute ischemic cerebrovascular disease (AICVD) after anticoagulation therapy. METHODS: Fifty-seven cases of AICVD were grouped and treated with heparin and Xueshuantong (XST) respectively, and the levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and activated protein C (APC) were determined before and after treatment. RESULTS: The clinical markedly effective rate in the heparin group and the XST group was 69.2% and 67.7% respectively with no significant difference (P > 0.05). In the heparin group, level of PT and APTT prolonged, FIB decreased, t-PA activity elevated and PAI activity lowered, and APC unchanged. In the XST group, same changes in FIB, t-PA and PAI were shown but with APC increased, and PT and APTT unchanged. CONCLUSION: Both heparin and XST have good anticoagulatory function and show good clinical effect in treating patients with hypertension complicated with acute ischemic cerebrovascular diseases.

PMID: 12577350 [PubMed - indexed for MEDLINE]

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Compound XueShuanTong Capsule is a compound Chinese herbal medicine that is composed of panax pseudo-ginseng, salvia miltiorrhizae and milkvetch root.
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 gibbledygook » Fri Sep 26, 2008 4:23 am

I've posted a lot of research on factors affecting vascular issues in MS partly because of my continued good response to salvia. In fact I've recently increased the dose of salvia to 14g daily. I have also now reduced the other herbs to 3 pills 3 times daily which works out to be roughly 5.4g daily for scutellaria, rehmannia and curcumin. This is working out well. I have also stopped the alpha lipoic acid which seemed to increase stiffness. I think the salvia alone is effective.

Although I can't really decide about the alpha lipoic. I think in combination with the salvia very little alpha lipoic may be needed and I may be still taking too much at 1.5g daily. mmm. maybe just 250mg alpha lipoic 3 times daily.

On a different point entirely, the market action is making me feel distinctly queasy. I think we may be about to go very significantly lower. Unless congress steps up to the mark we are all going down. There is no money in the system to generate any economic growth. I think we are talking civil unrest, mass rioting etc etc. Disabled people should get door locks. And a gun.
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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Butterbur

Postby gibbledygook » Tue Sep 30, 2008 8:52 am

I tried butterbur yesterday. This herb is said to increase cerebral vascular vasodilation and is useful in migraine and allergy. I took 1.8g 3 times with the other herbs. It seemed to have both good and bad effects, a bit like the capsaicin. I noticed a real reduction in the painful tingling that I get in bed but then I noticed a few sharp stabbing pains in the right arm which I haven't had in ages. I also had a few phosphenes which I also haven't had in ages. Finally I also noticed more itchiness on my face which I haven't had in ages.
Today I haven't taken any butterbur to see if these symptoms reappear.

The salvia seems to have thoroughly changed my blood. Like my mother who also suffered from terrible MS, I bruise easily. Or at least I used to bruise easily. At the weekend I fell over owing to overgrowth of plants on a narrow stone path. I have had NO bruising. This is weird.

Thursday 2nd October 2008
I took no butterbur yesterday and when I went to bed I noticed quite a bit of painful tingling so decided to try the alpha lipoic again and took 500mg. After a while the painful tingling became milder but then I started having quite strong spasms which I haven't had in a while so I took 3 more curcumin and in about an hour they died down. Ho hum. I shall just stick to salvia, curcumin, skutellaria, rehmannia , the chinese tea, vitamin d, NAC and bioperine today to see what happens.

18:02 I went for a session of hydrotherapy today which felt great in the water. Unfortunately the hospital was very overheated so when I sat down I felt very hot and walking wasn't very easy. It was when walking outside on a beautiful cold day that I realised that something has changed. My right foot especially feels very spongy and there is quite a lot of tingling in the left knee area but also variably in the feet. I cannot really tell yet whether this is good or bad. Later when I was a bit cooler I walked 400 meters to and fro the shop pretty well but still felt this curious sponginess, not dissimilar to when I took lots of ashgawanda. Mmm. I need a drink. I have been doing really well not drinking alcohol. The markets are on a knife edge. What will Congress do????? Will narrow self-interest and desperation to keep their seats mean they don't pass an admittedly shockingly badly structured bail-out? Why did Paulson not go for an equity warrant deal like Buffett with Goldman? Oh my god. AAAAAAAGH! 8O

Friday 3 October 2008
So I succumbed to half a bottle of wine last night and it was absolutely delicious. I woke up today with a rather stiffer right leg than I've had in a while. I immediately downed my morning herbs and then took my lunch time herbs rather earlier. The stiffness has now significantly improved. I am now beginning to wonder if my symptoms would get even better on even more salvia...but I'm already taking just over 14grams a day. That really should be the limit. I'm also wondering if my slight deteriorations this week were triggered by the butterbur experiment or perhaps inadequate salvia. Well I shall just have to repeat the experiment. But first a weekend of 14g of salvia, plus some 9 pills of curcumin, 9 of rehmania, 9 of scutellaria.
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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Gingko experiment

Postby gibbledygook » Tue Oct 07, 2008 10:09 am

I have decided to experiment with the gingko biloba rather than repeat the butterbur experiment which didn't seem to go well. I have just started 6.2g daily of gingko to go with the 14g of salvia, 6g of curcumin, 6g of rehmannia, 6g scutellaria, 30mg bioperine, NAC, vit d etc. I will go back to butterbur but first I must find another good herb.

7/10/08
Well, I had very spasms last night and today my leg is much stiffer than is usual. I think I will stop the gingko experiment and I will also now reduce the salvia as I think maybe too much salvia at 14g a day may be also making things harder. So I will reduce down to 10.8g daily with just 3 pills 6 times a day. This is a bit of a pain as I had been taking 6 pills just 4 times a day. Mmmm!

8/10/2008
I stopped the gingko 2/3 through yesterday and also reduced my salvia from 14.4g per day to 10.8g I still had quite bad spasms last night but they resolved after 6 pills of curcumin which has always been or seemed to be remarkably effective at reducing spasms.
I am already feeling better about this dosage. At the 14.4g dosage I could detect twinges in my kidney area. I know the herb is active in the kidneys so I think 14g is probably too much. In addition I think too much of vasodilation may be as bad as too much vasoconstriction which I believe is the problem in MS. So this might explain why over the last week or so (I upped the dose to 14.2g about 2 weeks ago) I have been suffering spasms and also more tingling in the left kneee area. (Or of course the herbs aren't working at all! However my reaction about a month ago to the salvia within 24hours suggests not.) Working out the right dose for salvia, curcumin and scutellaria is my aim over the next few weeks. Then I will resume my trials of butterbur, gingko etc. I had also reduced the dose of curcumin and scutellaria over the last few weeks as I had expected the salvia in higher dose would do the trick but this is not so. So I am now going to take 6 pills of the curcumin and 6 of the scutellaria 3 times a day with the salvia. This works out at 7.2g of the expensive life extension curcumin and 10.2g of the scutellaria.

13/10/2008
I have had great results from my experiment. High dose salvia should be avoided. I reduced the dosage from 14.4g daily to 7.2g and could within hours feel an improvement in the tingling and walking. Amazing. So I also decided to cut out everything except the curcumin and bioperine which we KNOW to be effective in reducing inflammation. The question now arised what is the ideal dose of salvia. After about 3 days of just 7.2g daily I find that my right leg is quite stiff and unlike the glorious experience on 10g when the spasticity, pain etc all reduced. I know have a bit more brain fog as well which I hadn't noticed before. What I might do is add 5.4g of gingko biloba to 5.4g of salvia and see what happens then. Gingko should further reduce BBB permeability:
1: Acta Pharmacol Sin. 2004 Oct;25(10):1306-11.Links
Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro.Qiu Y, Rui YC, Li TJ, Zhang L, Yao PY.
Department of Pharmacology, School of Pharmacy, Second Medical Military University, Shanghai 200433, China.

AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125I-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125I-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases. Copyright 2004 Acta Pharmacologica Sinica

PMID: 15456532 [PubMed - indexed for MEDLINE]

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And is also vasodilatory:
1: Phytomedicine. 2008 Mar;15(3):164-9. Epub 2008 Feb 6. Links
Ginkgo biloba extract improves coronary blood flow in healthy elderly adults: role of endothelium-dependent vasodilation.Wu Y, Li S, Cui W, Zu X, Du J, Wang F.
Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang 050000, PR China. wuyuzhou@medmail.com.cn

Advancing age decreases endothelial function; accordingly, it alters the physiological regulation of coronary blood flow. Ginkgo biloba extract (GBE) has well-documented anti-ageing effects. However, little is yet known about the pharmacological actions of GBE on endothelial dysfunction and coronary blood flow in healthy elderly adults. We designed the study to test the effects of GBE on distal left anterior descending coronary artery (LAD) blood flow and endothelium-dependent brachial artery flow-mediated dilation (FMD) in healthy elderly adults. Sixty healthy elderly adults were randomly assigned to either GBE or control groups. LAD blood flow and brachial artery FMD were measured non-invasively using high-resolution ultrasound before and after intravenous administration of GBE or saline. GBE significantly increased LAD blood flow in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with the placebo group (19.16+/-13.91% vs. 0.30+/-2.55%, 17.76+/-14.56% vs. 0.53+/-2.32%, and 21.73+/-16.13% vs. 0.81+/-2.33%, MDPV, MSPV, and DTVI improvement from baseline, respectively, p<0.01). Brachial artery FMD was also increased by 56.03% (from 7.21+/-2.52% to 11.28+/-3.95%, p<0.01). A linear correlation was found between the percentage change in MDPV, MSPV, or DTVI of LAD blood flow and the percentage change in brachial artery FMD following treatment with GBE (r=0.538, 0.366, or 0.573, respectively, p<0.01, p<0.05, or p<0.01). Our data demonstrate that GBE treatment in healthy elderly adults leads to the increase of LAD blood flow in MDPV, MSPV and DTVI, and the increased response might relate to the improved endothelium-dependent vasodilatory capacity. This study implies an important future therapeutic strategy of using GBE to counteract the detrimental effects of ageing.

PMID: 18258419 [
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Gingko is also nerve regenerative:
1: Microsurgery. 2007;27(8):673-7. Links
A dose-effect relationship of Ginkgo biloba extract to nerve regeneration in a rat model.Lin H, Wang H, Chen D, Gu Y.
Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

The effect of Ginkgo biloba extract (EGb(50)) on nerve regeneration and its dose-effect relationship was investigated in a rat model. Sciatic nerve transection and repair was done in 120 Sprague-Dawley rats. The animals were divided into four groups and given normal saline, low-dose EGb(50) (50 mg kg(-1) d(-1)), moderate-dose EGb(50) (100 mg kg(-1) d(-1)), and high-dose EGb(50) (200 mg kg(-1) d(-1)), respectively. Electrophysiological, histological examinations, and functional evaluation were conducted at various postoperative intervals. Sensory regeneration distance, sciatic functional index (SFI), motor nerve conduction velocity, compound muscle action potential, axon regeneration index, and muscle mass were significantly higher in EGb(50) groups than in saline groups. All but SFI of those parameters were better in high-dose group when compared with those in moderate- and low-dose groups. EGb(50) has the effect of promoting regeneration of injured peripheral nerve.The higher the dose, the better the result.

PMID: 17941104 [PubMed - indexed for MEDLINE]

Related ArticlesIn vitro and in vivo effects of Ginkgo biloba extract EGb 761 on seeded Schwann cells within poly(DL-lactic acid-co-glycolic acid) conduits for peripheral nerve regeneration. [J Biomater Appl. 2004] Long-term effects of muscle-derived protein with molecular mass of 77 kDa (MDP77) on nerve regeneration. [J Neurosci Res. 2005] Leukemia inhibitory factor enhances the regeneration of transected rat sciatic nerve and the function of reinnervated muscle. [J Neurosci Res. 1997] Effect of chronic cyclosporine administration on peripheral nerve regeneration: a dose-response study. [Ann Plast Surg. 2002] Ginkgo biloba extract (EGb 761) improves postischemic function in isolated preconditioned working rat hearts. [Coron Artery Dis. 1994] » See all Related Articles...
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Gingko also reduces soluble VCAM AND ICAM, one of which is upregulated during MS relapse (see above somewhere):

1: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 May;27(5):412-4.Links
[Effect of extract of Gingko biloba on soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 in patients with early diabetic nephropathy][Article in Chinese]


Li XS, Fu XJ, Lang XJ.
Medical college, Jinhua College of Profession and Technology, Zhejiang. jhwslxs@163.com

OBJECTIVE: To investigate the effect of extract of Gingko biloba (EGb) on soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with early diabetic nephropathy (DN). METHODS: Sixty-three patients with DN in early stage were randomly assigned to the control group (29 cases) and the treatment group (34 cases). Both groups were treated by routine treatment, and with EGb given to the treatment group additionally. The treatment course was 2 months. Serum sICAM-1 and sVCAM-1 were determined with ELISA before and after treatment, and urinary albumin excretion rate (UAER), fasting plasma glucose (FPG), serum creatinine (SCr) and blood lipids, etc. were examined as well. RESULTS: The levels of serum sICAM-1 and sVCAM-1 were significantly lower in both groups after treatment than those before treatment (P < 0.05 or P < 0.01), and the decrement in the treatment group was more significant than that in the control group (P < 0.01). And the levels of UAER, SCr and blood lipids decreased in the treatment group after treatment (P < 0.05 or P < 0.01). CONCLUSION: EGb could retard the development of early DN through decreasing the levels of serum sICAM-1 and sVCAM-1.
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This is off on a tangent but this herb affects the adrenal-pituitary system and may be helpful:

1: Biochem Pharmacol. 1986 Aug 1;35(15):2483-7.Links
Anti-inflammatory effect of saikogenin A.Cheng JT, Tsai CL.
Saikogenin A, an anti-inflammatory drug, is present in the crude extract of a Chinese herbal plant called Tsai-Fu. Saikogenin A was less effective in adrenalectomized rats than in normal rats in reducing the carrageenin-induced edema. Serum corticosterone and ACTH were increased in the saikogenin A-treated rats, supporting the view that stimulation of hypothalamopituitary-adrenal system is responsible for the anti-inflammatory effect of saikogenin A. This is further supported by the findings that saikogenin A did not affect the spontaneous release of corticosterone but it facilitated the ACTH-induced release. In addition, cyclic AMP in isolated pituitary and adrenal glands was increased by saikogenin A. A role for cyclic AMP as the second messenger is thus considered. Otherwise, the direct action of saikogenin A on the process of inflammation cannot be ruled out because saikogenin A also functioned in the adrenalectomized rats and it inhibited the release of histamine induced by compound 48/80. Reduction of the vascular permeability was also observed in the saikogenin A-treated rats. These results suggest that the anti-inflammatory action of saikogenin A are due to an increase in corticosterone caused by the release of ACTH and a direct effect on the process of inflammation.

PMID: 2427082 [PubMed - indexed for MEDLINE]
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saikosaponins are found in bupleurum.

This is interesting, gingko reduces t lymphocyte proliferation:
1: Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006 Jun;26 Suppl:47-50.Links
[Effects of ginkgo biloba extract on proliferation and apoptosis of T lymphocytes in vitro in rats with asthma][Article in Chinese]


Tang YJ, Xu YJ, Zhang ZX.
Department of Respiratory Diseases, Affiliated Tojgfi Hospital to Tongji Medical College, Huazhoug University of Science and Technology, Wuhan.

OBJECTIVE: To explore the partial therapeutic mechanism of Ginkgo Biloba extract (GBE) in treating asthma. METHODS: Fourteen SD rats were randomly divided into two groups, 7 rats were sensitized as the asthmatic model group and the others taken as the healthy control group. T lymphocytes were isolated from peripheral blood mononuclear cells (PBMCs) of the rats, and were cultured in vitro with Ginkgolide B (BN-52021 group) or Ginkgo Biloba extract 761 (EGb761 group) in different concentrations or without any of them (control group). T lymphocytes proliferation in groups were measured by using MTT assay and the effect of BN-52021 on T lymphocytes apoptosis was analyzed by flow cytometry at various times. RESULTS: Compared with the control group, BN-52021 could significantly inhibit the proliferation of T lymphocytes in both healthy and asthmatic rats in vitro (P <0. 05). The effects were enhanced as the concentration increasing and the time prolonging, the effects to the latter were higher than those to the former, showing significant difference between them ( P <0.05 ). However, the effect of EGb761 was varied with the concentrations. EGb761 could promote T lymphocytes proliferation at low concentration but inhibit it at high concentration, there was a significant difference as compared with that in the control group ( all P < 0. 05). The apoptotic rate of T lymphocytes rose as the concentration of BN-52021 increasing (P < 0. 01). CONCLUSION: GBE has different effects on T lymphocytes proliferation since the different ingredients and the concentrations in vitro, and it also has different effects between healthy and asthmatic rats. Ginkgolide B is the main active ingredient among them, it can not only inhibit T lymphocytes proliferation but also increase the apoptotic rate.

PMID: 17569345 [PubMed - in process]
link

More on gingko:
1: Cardiovasc Hematol Disord Drug Targets. 2006 Dec;6(4):279-304. Links
Anti-inflammatory effects of different drugs/agents with antioxidant property on endothelial expression of adhesion molecules.Chen YH, Lin SJ, Chen YL, Liu PL, Chen JW.
Institute of Clinical Medicine, National Yang-Ming University, Taiwan, Republic of China.

Atherosclerosis is a chronic inflammatory process. The adhesion of leukocytes to the vascular endothelium, mediated by endothelial cell adhesion molecules including vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, is the pivotal early event in atherogenesis. Inflammatory cytokines could activate redox-sensitive transcription factors and induce endothelial expression of adhesion molecules, which could be inhibited to various degrees by different antioxidants suggesting the potential role of endogenous reactive oxygen species (ROS) in atherogenesis. Many clinical drugs that against cardiovascular diseases have exhibited antioxidant effects; these drugs simultaneously inhibit endothelial adhesion molecule expression, such as aspirin, probucol, HMG-CoA reductase inhibitors, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha and gamma ligands, calcium channel blockers, beta-adrenergic blockers, etc. In addition, we have previously demonstrated that Ginkgo biloba extract, a Chinese herb with antioxidant activity, could significantly suppress inflammatory cytokine-stimulated endothelial adhesiveness to human monocytic cells by attenuating intracellular ROS formation, redox-senstive transcription factor activation, and VCAM-1 as well as ICAM-1 expression in human aortic endothelial cells. The similar anti-atherosclerosis effects have been also shown in other Chinese herbs or dietary supplements with antioxidant activity such as magnolol and salvianolic acid B either in vitro or in vivo. Thus, oxidative stress is critical to endothelial adhesiveness in atherogenesis. The inhibition of endothelial adhesion molecule expression by drugs/agents with antioxidant activity may serve as a potential therapeutic strategy for clinical atherosclerosis.

PMID: 17378773 [PubMed - indexed for MEDLINE]
link
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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Gingko biloba

Postby gibbledygook » Tue Oct 14, 2008 1:00 am

The replacement of half the 10.8g of salvia with 5.4g of gingko was interesting. It provoked quite a large amount of leg tingling during the day which worried me quite a bit so I took some scutellaria to calm things down a bit. By night time the tingling had died down somewhat and when I got into bed I had virtually no pain where normally there is quite a lot. I had a few spasms which died down after about 4 or 5 curcumin pills (400mg). Today my experiment is a further reduction of salvia to 3.6g daily with 3.6g of gingko biloba, 3.6 to 6g curcumin and 5.4g scutellaria. This morning my legs feel good with less stiffness. I think the gingko may be very good combined with the salvia because it reduces the vegf. Without an inhibitor of vegf like gingko the salvia may in fact cause vessel permeability after high doses as it may overly dilate the vessels. Just speculation. I feel that I'm really on the right path with these herbs as they have such a noticeable effect on my legs. :)

14/10/2008
Hoorah. Scarcely a spasm last night but a bit of pain in the legs. Walking felt good today around 11:40 but produced quite a lot of tingling in the left leg so took some more herbs and 40 minutes later the tingling has reduced even after a good 5 minutes walk. There is definitely something about the health of the vasculature that is involved in MS. We need plenty of VEGF inhibitors, I reckon.

The five minute walk and tingle test is useful. I have just completed another 5 minute walk at 3.30 and the tingling has been relatively subdued. I am now going to take another 1.2g of gingko and see how the 5 minute tingles work!

I have just completed another 5 minute walk/tingle test and I have very nearly NO tingling after the walk. Clearly the gingko is preventing the permeability of the blood vessels. I have always imagined the tingling as the sensation of blood beating past the nerve as it has that movement in it. I think all hands to the anti VEGF deck!

17/10/2008
I had no spasms yesterday after 4.8g gingko, 3.6g salvia, 3.6g curcumin, 5.4g scutellaria. I have noticed over these last few nights a lighter sleep pattern with much more vivid dreams.


I had an angry interchange with a Herbal Extracts Plus customer service employee when I told her that the herbs they had sent were clearly not the same in appearance or smell to the same herbs that they had sent before. She blamed alterations in the plants and claimed it was all natural. What bullshit. I buy herbs regularly and know that their appearance, smell and taste may vary only marginally not be so completely different. I have totally lost confidence in this company. This is very annoying as I had just put in a large order for the salvia. If I can get my vindictive juices going I shall spread this information about as many websites as I can but have so far limited my action to the Federal Drug Agency and something called the Consumer Lab which monitors supplements for consumers.

I have found an alternative website which looks very high quality and is: http://www.discountvitaminsandherbs.com

I only hope that they prove more reliable than herbal extracts plus.

Gingko is good for reducing coagulation:
1: Biomed Environ Sci. 2006 Aug;19(4):249-53.Links
Activity of Ginkgo biloba extract and quercetin on thrombomodulin expression and tissue-type plasminogen activator secretion by human umbilical vein endothelial cells.Lan WJ, Zheng XX.
Key Laboratory for Biomedical Engineering of Ministry of Education of China, Zhejiang University (Yuquan Campus), Hangzhou 310027, Zhejiang, China. lanwenjun0522@hotmail.com

OBJECTIVE: In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thrombomodulin (TM) expression and tissue-type plasminogen activator (t-PA) secretion was studied. METHODS: Using flow cytometer and gel image system respectively, we evaluated the TM expression and the t-PA secretion by human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS: The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly. CONCLUSION: The effect of GBE on improving blood circulation may be partly attributed to its promoting TM expression and t-PA secretion by endothelial cells, and quercetin participated in the effect of GBE on t-PA secretion. However, the action of GBE on increasing TM expression needs further study.

PMID: 17044640 [PubMed - indexed for MEDLINE]

link

from wikipedia today 17/10/08
Thrombomodulin, CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells.

The protein has a molecular mass of 74kDa, and consists of a single chain with 5 distinct domains.

It functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect. The TT-complex also stimulates fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI) into its active form.

The antigen described as BDCA-3[1] has turned out to be identical to thrombomodulin.[2] Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human dendritic cells called MDC2. Its function on these cells is unknown at present, but apparently, thrombomodulin has at least one other ligand apart from thrombin, because anticoaglulation is a commonplace function, in contrast to the rarity of MDC2 cells.


I must admit that the gingko has produced an amazing and immediate effect which I have never noticed whilst sampling quercetin, albeit in rather low dose of say 3g per day.

The fact that thrombomodulin is identical to BDCA-3 had me trying to find out stuff there and I came across this which shows that BDCA-2 and BDCA-4 are low in MS.

1: Mult Scler. 2008 Jul 24. [Epub ahead of print] Links
Multiple sclerosis: reduced proportion of circulating plasmacytoid dendritic cells expressing BDCA-2 and BDCA-4 and reduced production of IL-6 and IL-10 in response to herpes simplex virus type 1.Sanna A, Huang YM, Arru G, Fois ML, Link H, Rosati G, Sotgiu S.
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy.

Objective We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses. Methods We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN-gamma), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-alpha and beta, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1). Results The subset of lineage negative (lin(-)), BDCA-2(+) cells was lower in patients with MS compared with HC (0.08 +/- 0.02% vs 0.24 +/- 0.02%; P < 0.001). A similar pattern was observed for lin(-)BDCA-4(+) cells (0.08 +/- 0.02% vs 0.17% +/- 0.03; P < 0.01). Spontaneous productions of IL-6 (45 +/- 10 pg/mL vs 140 +/- 26 pg/mL; P < 0.01) and IL-10 (17 +/- 0.4 pg/mL vs 21 +/- 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 +/- 0.15 pg/mL vs 21 +/- 5 pg/mL; P < 0.01 and IL-10 (11 +/- 1 pg/mL vs 14 +/- 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN-alpha, IL-6, and IL-10 but decreased production of IL-4. In response to HSV-1 exposure, productions of IL-6 (165 +/- 28 pg/mL vs 325 +/- 35 pg/mL; P < 0.01) and IL-10 (27 +/- 3 vs 33 +/- 3 P < 0.05) by MNC as well as by pDC (IL-6: 28 +/- 7 vs 39 +/- 12 P < 0.05; IL-10: 14 +/- 1 vs 16 +/- 3 P < 0.05) were lower in patients with MS compared with HC. Conclusion The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.

PMID: 18653740 [PubMed - as supplied by publisher]
link

and this:
1: Eur Rev Med Pharmacol Sci. 2000 May-Jun;4(3):59-66.
Clinical importance of thrombomodulin serum levels.Califano F, Giovanniello T, Pantone P, Campana E, Parlapiano C, Alegiani F, Vincentelli GM, Turchetti P.
Department of Clinical Sciences, Policlinico Umberto I, Università La Sapienza, Rome, Italy.

Thrombomodulin is a glycoprotein that can bind to thrombin and activate protein C, thus mitigating the effects of cytokines produced by inflammatory and immunological processes. The molecule exerts a protective function on endothelial cells. Thrombomodulin is cleaved to its soluble form by neutrophil elastase and by other substances produced during acute and chronic inflammatory responses, immunologic reactions and complement activation. ELISA technique yields normal serum levels of 3.1 +/- 1.3 ng/ml; in males these levels are higher; TM levels also rise during menopause. Other circumstances associated with an increase of serum TM levels are smoking, disseminated intravascular coagulation (DIC), cardiac surgery, atherosclerosis, ARDS, liver cirrhosis, diabetes mellitus, cerebral and myocardial infarction, and multiple sclerosis. Serum levels of TM represent an useful prognostic index, because they are associated with an increase in mortality rate, or however a progression of the underlying pathological condition.

PMID: 11558626 [PubMed - indexed for MEDLINE]
link

1: J Neuroimmunol. 1995 Jan;56(1):113-6. Links
Thrombomodulin in the sera of patients with multiple sclerosis and human lymphotropic virus type-1-associated myelopathy.Tsukada N, Matsuda M, Miyagi K, Yanagisawa N.
Department of Health Medical Center and Neurology, Shinshu University, Matsumoto, Japan.

Damage to the blood-brain barrier, which mainly consists of cerebral endothelial cells, has been demonstrated in multiple sclerosis (MS) clinically and histochemically. To investigate the endothelial cell damage, we evaluated the presence of soluble thrombomodulin in the sera of patients with MS and human T lymphotropic virus type-1-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay. Serum thrombomodulin levels were significantly increased in patients with acute relapsing MS during an exacerbation and chronic progressive MS as compared with those of controls (P < 0.001, respectively). Patients with HAM also had higher serum levels of thrombomodulin than did controls (P < 0.001). There was significant difference between patients with HAM and seropositive non-HAM carriers (P < 0.01). These results suggest that the detection of serum thrombomodulin could be used as a marker of endothelial cell damage in inflammatory diseases such as MS and HAM.

PMID: 7822477 [PubMed - indexed for MEDLINE]
link
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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Gingko etc

Postby gibbledygook » Sat Oct 18, 2008 7:31 am

I had another great night of no spasms and awoke with only moderate stiffness. This is on 4.8g of gingko. I have just done a bit of walking and noticed moderate tingling afterwards. I took the gingko a few hours ago so it should be in the blood stream. I have just taken 1.2g of horsechestnut to see how this combines with the gingko to strengthen the veins/capillaries. I also have hesperidin to test.

I have also just taken an additional 1.2g of gingko to see how the tingling goes, if it goes! This will mean 6g of gingko daily. I notice the Chinese Materia Medica states that up to 9g is safe. I think the gingko probably gives one quite vivid dreams. I have certainly had several over the past few nights.

Over the course of the next few days gingko from life extension, from simply supplements and a brand from iherb will be arriving. These have much lower absolute mg than the herbalextractsplus gingko so I shall just have to experiment to see which brand to stick with and what amount is best to take. According to Simply supplements 120mg is the equivalent to 6g of the dried herb, which is what I think herbalextractsplus provide. So I will have to stop my horsechestnut experiment and concentrate on the "standardized forms" of gingko which I have just ordered. :?

20/10/2008
Well, looking at the different information from the various gingko suppliers, it seems that they all have exactly same percentage of glycolides and terpenes as herbalextractsplus but in much lower dosage. Great. I have lost confidence in herbalextracts but they are the only supplier with decent dosages of gingko. But what if they are not supplying gingko but some other herb?! That is my fear with herbalextractsplus.

It's been an hour since I took 5x 120mg of the Doctor's Best gingko and I have also just completed my 5 minute walk/tingle test. This has produced subdued tingling which stopped fairly quickly. My next dose will be 10 x 120mg of this gingko.

I have been naughtily avoiding my Chinese tea but the last time I had it on Thursday it made me barf it was so disgusting. Strangely I've managed to get through 2 pots of the stuff without this sudden aversion. mmm. Maybe the gingko is interfering?
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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