Psoriasis: The Number One Suspect - EDHF
cruiser
characteristic or symtomatic of mutiple diseases. (Heart disease,
Cancer, Diabetes, IBS, MS, psycholigical disorders, Psoriasis, CFS,
Renal disease, ME...)
People with one of these diseases are considerd to be at higher risk
of developing other of the diseases that exhibit endothelial
dysfunction and anemia.
I propose that endothelial dysfunction and anemia are the actual
disease, and that the mutiple diseases, where endothelial dysfunction
and anemia are considered symtoms, are themselves actually the symtoms
of the disease endothelial dysfunction, complicated by anemia.
Endothelial dysfunction is best characterized by a failure of EDHF to
provide vasodilation, when arginase prevents NO mediated
vasodialation.
Unmitigated constriction of microvasculature in tissues leads to a
shortage of oxygen which impairs immune function, detoxification,
lipid metabolism, brain signalling, and energy production. Shortage of
oxygen ironically leads to oxidative stress, since the body cannot
properly detox.
Anemia contributes to this problem.
Correction of endothelial dysfunction involves correcting the failure
of EDHF to provide vasodilation.
When considering endothelial dysfunction the disease, there is the
implication that if endothelial function is corrected in early stage,
then these diseases will be prevented.
There is further implication that even after prolong endothelial
dysfunction, correction of the condition will prevent the further
advancement of these symtomatic diseases, and in some cases even
reverse the course of the symtomatic diseases to provide remission.
It must be recongnized that prolonged endothelial dysfunction spanning
years or even decades, may cause some irreversible damage, that cannot
be corrected simply by curing endothelial dysfunction.
Symtomatic diseases that would be expected to be most difficult to
reverse by curing endothelial dysfunction are cancer, heart disease,
and diabetes. Effort should be focused on prevention of endothelial
dysfunction and early stage treatment to prevent cancer, heart
disease, and diabetes from developing.
http://www.ncbi.nlm.nih.gov/pubmed/9389744
Importance of endothelium-derived hyperpolarizing factor in human
arteries.Urakami-Harasawa L, Shimokawa H, Nakashima M, Egashira K,
Takeshita A.
Research Institute of Angiocardiology and Cardiovascular Clinic,
Kyushu University School of Medicine, Fukuoka, Japan.
The endothelium plays an important role in maintaining the vascular
homeostasis by releasing vasodilator substances, including
prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived
hyperpolarizing factor (EDHF). Although the former two substances have
been investigated extensively, the importance of EDHF still remains
unclear, especially in human arteries. Thus we tested our hypothesis
that EDHF plays an important role in human arteries, particularly with
reference to the effect of vessel size, its vasodilating mechanism,
and the influences of risk factors for atherosclerosis. Isometric
tension and membrane potentials were recorded in isolated human
gastroepiploic arteries and distal microvessels (100-150 microm in
diameter). The contribution of PGI2, NO, and EDHF to endothelium-
dependent relaxations was analyzed by inhibitory effects of
indomethacin, NG-nitro- L-arginine, and KCl, respectively. The nature
of and hyperpolarizing mechanism by EDHF were examined by the
inhibitory effects of inhibitors of cytochrome P450 pathway and of
various K channels. The effects of atherosclerosis risk factors on
EDHF-mediated relaxations were also analyzed.
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The results showed that (a) the contribution of EDHF to endothelium-
dependent relaxations is significantly larger in microvessels than in
large arteries;
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(b) the nature of EDHF may not be a product of cytochrome P450
pathway,
##################################################
while EDHF-induced hyperpolarization is partially mediated by calcium-
activated K channels; and (c) aging and hypercholesterolemia
significantly impair EDHF-mediated relaxations. These results
demonstrate that EDHF also plays an important role in human arteries.
PMID: 9389744 [PubMed - indexed for MEDLINE]
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This is the problem causing psoriasis, and psoriasis will go away when
this is fixed.
cruiser
cruiser
Gap junction-dependent increases in smooth muscle cAMP underpin the
EDHF phenomenon in rab
HJ Taylor, AT Chaytor, DH Edwards, TM Griffith
Department of Diagnostic Radiology, University of Wales College of
Medicine
We have investigated the role of cAMP in nitric oxide (NO)- and
prostanoid-independent vascular relaxations evoked by acetylcholine
(ACh) in isolated arteries and perfused ear preparations from the
rabbit. These EDHF-type responses are shown to be associated with
elevated cAMP levels specifically in smooth muscle and are attenuated
by blocking adenylyl cyclase or protein kinase A (PKA). Relaxations
are amplified by 3-isobutyl-1-methylxanthine, which prevents cAMP
hydrolysis, while remaining susceptible to inhibition by the
combination of two K(Ca) channel blockers, apamin and charybdotoxin.
Analogous endothelium- and cAMP-dependent relaxations were evoked by
cyclopiazonic acid (CPA) which stimulates Ca(2+) influx via channels
linked to the depletion of Ca(2+) stores. Responses to ACh and CPA
were both inhibited by interrupting cell-to-cell coupling via gap
junctions with 18alpha-glycyrrhetinic acid and a connexin-specific Gap
27 peptide.
###########################################
The findings suggest that EDHF-type responses are initiated by
capacitative Ca(2+) influx into the endothelium and propagated by
direct intercellular communication to effect relaxation via cAMP/PKA-
dependent phosphorylation events in smooth muscle.
###########################################
Cruiser
cruiser
Got it!!
-----
http://www.lef.org/newsletter/2008/0108_heart-disease-linked-to-vitamin-d-deficiency.htm
"Vitamin D receptors have a broad tissue distribution that includes
vascular smooth muscle and endothelium, the inner lining of the body's
vessels.
---------------------------
So, going back to the previous thread....
---------------------------
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=51033
Calcitriol causes a rapid accumulation of cGMP, dependent on the
presence of normal vitamin D receptors (VDRs).
------------------
http://ntrs.nasa.gov/search.jsp?R=427193&id=9&qs=No%3D140%26Ne%3D35%2...
Our work centered on one particular target of 1,25(OH)2D3 action, the
voltage-sensitive calcium channels (VSCC's), which are activated
acutely by this steroid within milliseconds of exposure .
-------------------------------------------
So there are vitamin D receptors on endothelial cells and vascular
smooth muscle cells.
So, this strongly suggests that high dose vitamin D3 may trigger
systemic vasodilation, particularly in the microvasculature, improving
oxygen delivery to hypoxic tissues, and lowering blood pressure.
Vitamin D3 may act in two ways to accomplish this:
1) direct cGMP accumulation in the vascular smooth musle cells,
stimulated by vitamin d, directly.
2) calcium influx into the endothelial cells activating EDHF, which in
turn causes an accumulation of cGMP in vascular smooth muscle cells.
Now Uwe said that you had to take two things together for it to work.
So, it might be time to consider what other supplement, besides
vitamin D3 is needed to make it work.
Calcium?
It seems that correcting potential anemia may be a good idea.
Iron?
folic acid?
A nutrient mix?
Niacin?
Vitamin C?
Boron?
I will try just some Cod Liver Oil, with some vitamin D3 1000IU,
tonight to judge the reaction.
I am taking Cod liver Oil with the D3 since vitamin D3 is oil soluable
and needs oil to be absorbed. It may just be that simple.
After that I may try to pair different things with that original
combination, until I see some sort of obvious postitive result.
Cruiser
cruiser
> I will try just some Cod Liver Oil, with some vitamin D3 1000IU,
> tonight to judge the reaction.
> Cruiser
BTW, I meant with vitamin D3 pills, each 1000IU.
cruiser
cruiser
D2 is catabolized much sooner than D3 (at least in chicks) and is not
as readily converted to the 25OH form in overdose situations. Perhaps
that is why D3 is more than 10 times as toxic as D2.
<snip>
Dietary overdose of vitamin D results in relatively successful
shutdown of 1-hydroxylation, but 25OH D builds up to such high levels
that
#############################
it begins to overwhelm and turn on 1,25 OH D receptors around the body
without being further hydroxylated.
#############################
------------------------------------------------
I take this as an indication that it will cause system calcium influx
into cells, including endothelial cells, and should cause systemic
vasodilation.
It seems, that you need to take close to the toxic amount without
going over the edge.
cruiser
cruiser
Psoriasis and altered calcium metabolism: downregulated capacitative
calcium influx and defective calcium-mediated cell signaling in
cultured psoriatic keratinocytes.Karvonen SL, Korkiamäki T, Ylä-
Outinen H, Nissinen M, Teerikangas H, Pummi K, Karvonen J, Peltonen J.
Department of Anatomy and Cell Biology, University of Oulu, Oulu,
Finland. seija-liis...@oulu.fi
Intracellular calcium plays an important part in the regulation of
proliferation and differentiation of keratinocytes. Detached from
their in vivo environment, cultured psoriatic keratinocytes were
investigated by monitoring free intracellular calcium concentration,
which was measured using fura-2/AM as a calcium-sensitive probe.
###################################################################################
The mean increase in intracellular calcium of psoriatic keratinocytes
was significantly reduced compared with control keratinocytes when
intracellular calcium stores were mobilized from endoplasmic reticulum
with thapsigargin. This finding suggests defective capacitative
calcium influx of psoriatic cells.
###################################################################################
Intracellular calcium stores were similar in psoriatic and control
keratinocytes, when extracellular calcium was chelated with
ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid
and intracellular calcium was depleted with thapsigargin. Mechanical
wounding of keratinocyte monolayer resulted in a significantly reduced
rise in intracellular calcium of psoriatic cells in low (< 0.1 mM) and
high (1.8 mM) extracellular calcium suggesting defective intercellular
coupling of psoriatic keratinocytes. Blocking of gap-junctions with
heptanol in wounded keratinocytes did not affect the intracellular
calcium response in psoriatic keratinocytes in contrast to healthy
keratinocytes.
###################################################################################
Adding adenosine triphosphate to culture medium resulted in a more
pronounced intracellular calcium increase than thapsigargin in
psoriatic keratinocytes, suggesting that inositol triphosphate-
mediated, P2-purinergic signaling was enhanced in these cells.
###################################################################################
Moreover, psoriatic keratinocytes maintained their defective responses
up to at least fifth passage suggesting that psoriatic keratinocytes
have an inborn error in calcium metabolism, rather than a localized
defect in response to altered extracellular calcium gradient observed
in vivo.
cruiser
cruiser
http://www.endocrine-abstracts.org/ea/0014/ea0014p275.htm
Effect of vitamin D replacement on endothelial function and oxidative
stress in vitamin D deficient subjects
Ozlem Tarcin1, Dilek Yavuz1, Ahmet Toprak2, Ahu Telli3, Meral Yuksel4,
Dilek Yazici1, Seda Sancak1, Oguzhan Deyneli1, Goncagul Haklar3 & Sema
Akalin1
1Marmara University Medical School Section of Endocrinology and
Metabolism, Istanbul, Turkey; 2Marmara University Medical School
Department of Internal Medicine, Istanbul, Turkey; 3Marmara University
Medical School Department of Biochemistry, Istanbul, Turkey; 4Marmara
University Vocational School of Health Related Sciences, Istanbul,
Turkey.
-------------------------------------------------
Introduction: Vitamin D (Vit D) receptors have been shown in extra
skeletal tissues. Vit D deficiency plays a role in the development of
many malignant, chronic inflammatory, autoimmune and metabolic
diseases. Our aim was to evaluate the effect of Vit D replacement
therapy on insulin sensitivity, endothelial function and oxidative
stress in Vit D deficient subjects.
Material-method: Serum 25(OH) D levels of 74 volunteer-healthy
subjects (22.7±2.7) were screened. Twenty subjects (22.6±2.1) with
25(OH) D levels < 20 ng/ml were recruited as deficient group (D) and
20 subjects (23±2.3) with 25(OH) D levels >40 ng/ml were selected as
control group (C). Monthly 300 000 IU Vit D was injected for 3 months
to group D. Before and after 3 months, blood samples were collected
for serum Ca, P, iPTH, thiobarbituric acid reactive substance (TBARs)
and paraoxonase. Endothelial function was evaluated by measuring flow
mediated dilatation (FMD) from brachial artery. Insulin sensitivity
index was calculated according to 75gr OGTT.
Results: In group D, basal TBARs levels were higher compared to group
C and decreased after Vit D therapy (Table 1). Basal FMD of group D
were found to be lower than group C and increased after therapy. We
found negative correlation between FMD and TBARs (P=0.001; r=-0.51) in
group D. After therapy, 30th sec. insulin level increased during OGTT.
Table 1 Parameters before and after replacement therapy Before
therapy After therapy Control
iPTH(pg/ml) 47.8±22.5* 34±17.6 42.8±12.2
Ca(mg/dl) 9.6±0.7 9.7±0.4 9.8±0.4
P(mg/ml) 3.8±0.4 3.8±0.5 3.7±0.4
FMD(%) 7.2±4* 10.5±4 13±12.6**
TBARs(nmol/mg MDA) 5±1.5* 3±0.7 4±0.8**
*P<0.05 before and after therapy; **P<0.05 before therapy and control
Discussion: We have shown that vit D deficiency causes endothelial
dysfunction. Vit D replacement led to the improvement on endothelial
function and decreased lipid peroxidation which made us think that vit
D deficiency could have take part in the pathogenesis of
atherosclerosis.
Cruiser
cruiser
Aims To test whether a single large dose of vitamin D2 can improve
endothelial function in patients with Type 2 diabetes mellitus and low
serum 25-hydroxyvitamin D levels.
Methods Double-blind, parallel group, placebo-controlled randomized
trial. A single dose of 100 000 IU vitamin D2 or placebo was
administered to patients with Type 2 diabetes over the winter, when
levels of circulating 25-hydroxyvitamin D were likely to be lowest.
Patients were enrolled if their baseline 25-hydroxyvitamin D level was
< 50 nmol/l. Endothelial function and blood pressure were measured and
fasting blood samples were taken at baseline and 8 weeks after
administration of vitamin D.
Results Forty-nine per cent of subjects screened had 25-
hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed
the study, with a mean age of 64 years and a baseline 25-
hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation
increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to
placebo and significantly improved flow mediated vasodilatation (FMD)
of the brachial artery by 2.3%. The improvement in FMD remained
significant after adjusting for changes in blood pressure. Vitamin D
supplementation significantly decreased systolic blood pressure by 14
mmHg compared with placebo; this did not correlate with change in FMD.
Conclusions Vitamin D insufficiency is common in patients with Type 2
diabetes during winter in Scotland. A single large dose of oral
vitamin D2 improves endothelial function in patients with Type 2
diabetes and vitamin D insufficiency.
Cruiser
randall
Do you think that VDRs are broken some how? LOL
If we get plenty of sunshine and still flake, then either we
have to much TNF, to little EDHF or not enough T-regs to
turn the inflammatory factors down to a simmer?
In your understanding of EDHF will it turn off autoimmunity?
Or are the VDR's not responding and or being sapped? Then
why doesn't VD3 supplementation simply clear us up?
Lets find some current abstracts.
Here's one that just came available:
http://www.ncbi.nlm.nih.gov/pubmed/18290726?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Vitamin D receptor agonists in the treatment of autoimmune diseases:
selective targeting of myeloid but not plasmacytoid dendritic cells.
Penna G, Amuchastegui S, Laverny G, Adorini L.
BioXell, Milan, Italy.
Vitamin D receptor (VDR) agonists are well known for their capacity to
control calcium and bone metabolism and to regulate growth and
differentiation of many cell types. More recently, it has become clear
that VDR agonists possess immunoregulatory properties and, in
particular, pronounced protolerogenic activities. These agents have
been shown to be effective in several models of autoimmune diseases
and are the most used topical agents in the treatment of psoriasis, a
Th1 and Th17 cell-mediated autoimmune disease of the skin, indicating
their potential applicability in the treatment of a variety of
autoimmune diseases. VDR agonists can act directly on T cells, but
dendritic cells (DCs) seem to be their primary targets. A potentially
very important activity of VDR agonists is their capacity to induce in
vitro and in vivo tolerogenic DCs able to enhance CD4(+)CD25(+)
suppressor T cells that, in turn, inhibit effector T-cell responses.
Novel data now show that VDR agonists selectively modulate tolerogenic
properties in blood myeloid but not plasmacytoid DCs, shedding new
light on the multifaceted immunoregulatory properties of these agents.
PMID: 18290726
Are we to assume that Th17 is not only failing to make suppressor T
cells (Treg's)
but also we need more EDHF to hyperpolarize what exactly? And when
inflammation does simmer down, what turns off excess EDHF?
========================
Maybe you can explain the nature of EDHF, I haven't looked yet, in
relationship
to NGF in etiology of psoriasis in this next abstract.
http://www.ncbi.nlm.nih.gov/pubmed/18349121?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Revisiting the Koebner Phenomenon. Role of NGF and Its Receptor System
in the Pathogenesis of Psoriasis.
Raychaudhuri SP, Jiang WY, Raychaudhuri SK.
From the Veteran's Administration Medical Center and the Division of
Rheumatology, Allergy, and Clinical Immunology, University of
California Davis School of Medicine, Sacramento; and Stanford
University School of Medicine,* Stanford, California.
Nerve growth factor (NGF) influences the key pathological events of
psoriasis: keratinocyte proliferation, angiogenesis, and T-cell
activation. We have systematically examined the kinetics of NGF
expression, keratinocyte proliferation, and migration of T lymphocytes
in the epidermis in Koebner-induced developing psoriatic plaques. In
skin traumatized by the tape-stripping method (n = 12), a marked up-
regulation of NGF in Koebner-positive lesions (n = 7) was observed 24
hours after trauma. Synthesis of NGF reached its maximum level in the
2nd week. Furthermore, cultured keratinocytes from nonlesional skin of
psoriasis patients produced 10 times higher levels of NGF compared
with keratinocytes from healthy individuals. To substantiate the in
vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we
studied psoriatic plaques and normal human skin in a SCID-human skin
xenograft model. The transplanted psoriatic plaques demonstrated
marked proliferation of NGF-R (p75)-positive nerve fibers compared
with only a few nerves in the transplanted normal human skin. Our
results demonstrate that 1) in a developing psoriatic lesion, up-
regulation of NGF together with keratinocyte proliferation are early
events and precede epidermotropism of T lymphocytes; 2) keratinocytes
in patients with psoriasis are primed to produce elevated levels of
NGF; and 3) NGF synthesized by these keratinocytes is functionally
active.
PMID: 18349121
Understanding EDHF in regards to NGF as well as TNF and if it's due to
multifactorial genes and selectivity seems axiomatic and not merely
perfunctory. Certainly i'd still aver for the gene set being
compensatory
for inflammation simply as a means to avoid Th2 and cancer
ramifications
till we know or have a good gene (i mean BAD gene) to blame it on. LOL
---------------------------
Now let's look at monkeying around with these pathways and Pneumonia
as a side effect...
Abstracts:
http://www.ncbi.nlm.nih.gov/pubmed/18339457?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Caveat emptor:
[Acitretin-induced pneumonia: An underestimated complication of
treatment of psoriasis.]
[Article in French]
Martzolff L, Huber M, Dukic R, Thannberger P, Kieffer C, Kieffer P.
Service de médecine interne, centre hospitalier Saint-Morand, 68134
Altkirch cedex, France.
INTRODUCTION: Retinoids are known to induce side effects which can be
severe. Alveolar and interstitial pneumonia of uncertain pathogenesis
can rarely occur when retinoid are used among patients with psoriasis.
EXEGESIS: We report an observation of acute respiratory distress
beginning 26 days after introduction of acitretin, a second-generation
retinoid. Treatment withdrawal and corticotherapy allow a spectacular
amelioration of respiratory conditions. CONCLUSION: Pneumonia induced
by retinoid must be known as a side effect of treatment of psoriasis.
PMID: 18339457
--------------------------------------
I better post this one. It looks serious. LOL
http://www.ncbi.nlm.nih.gov/pubmed/18337836?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
FR255734, a Humanized, Fc-Silent, Anti-CD28 Antibody, Improves
Psoriasis in the SCID Mouse-Psoriasis Xenograft Model.
Raychaudhuri SP, Kundu-Raychaudhuri S, Tamura K, Masunaga T, Kubo K,
Hanaoka K, Jiang WY, Herzenberg LA, Herzenberg LA.
[1] 1Department of Genetics, Stanford University School of Medicine,
Stanford, California, USA [2] 2Division of Rheumatology, Stanford
University School of Medicine, Stanford, California, USA [3] 3Division
of Rheumatology, Allergy and Clinical Immunology, University of
California at Davis and VA Medical Center, Sacramento, California,
USA.
In psoriasis, CD28/B7 costimulatory molecules are well characterized.
Here, using the severe combined immunodeficient (SCID) mouse-psoriasis
xenograft model, we report therapeutic efficacy of a humanized anti-
CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc.,
Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were
treated weekly for 4 weeks with intraperitoneal injections of FR255734
at 10, 3, and 1-mg kg(-1) doses. Groups treated with doses of 10 and 3
mg kg(-1)had significant thinning of the epidermis and reduced HLA-DR-
positive lymphocytic infiltrates. The length of the rete pegs changed
from 415.2+/-59.6 to 231.4+/-40.4 mum (P<0.005) in the 10-mg kg(-1)
group, and from 323.4+/-69.6 to 237.5+/-73.6 mum in the 3-mg kg(-1)
group (P=0.002). Positive controls treated with CTLA4-Ig and
cyclosporine had significant histological improvement, whereas plaques
treated with saline and isotype controls (human and mouse IgG2)
remained unchanged. In vitro studies have shown that FR255734
effectively blocked T-cell proliferation and proinflammatory cytokine
production. These observations warrant studies to evaluate the
efficacy of FR255734 in human autoimmune diseases.Journal of
Investigative Dermatology advance online publication, 13 March 2008;
doi:10.1038/jid.2008.38.
PMID: 18337836
----------------------------------------
And I better put this out. Chinese herbs are like kung fu of medicine.
Chop, chop... already. <w>
http://www.ncbi.nlm.nih.gov/pubmed/18341576?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Chinese herbal medicine (Tuhuai extract) exhibits topical anti-
proliferative and anti-inflammatory activity in murine disease models.
Man MQ, Shi Y, Man M, Lee SH, Demerjian M, Chang S, Feingold KR, Elias
PM.
Dalian Skin Disease Hospital, Liaoning, China.
While psoriasis is one of the most common skin disorders in humans,
effective, safe and inexpensive treatments are still largely
unavailable. Chinese herbal medicine (CHM) has been used for centuries
for treating psoriasis and several reports claim that systemic
administration of one such CHM, Tuhuai, mainly composed of flos
sophorae, smilax glabra roxb and licorice, is effective in psoriasis.
However, the mechanisms by which this CHM improves psoriasis are not
yet clear. Two universal features of psoriasis are epidermal
hyperplasia and inflammation. Moreover, drugs that specifically
inhibit epidermal hyperplasia and/or inflammation are widely used to
treat psoriasis. Here, we investigated whether topical applications of
Tuhuai extract exhibit anti-proliferative and anti-inflammatory
activities in two murine models of inflammatory dermatoses. To assess
Tuhuai's potential anti-proliferative effect, we disrupted epidermal
barrier function twice-daily for 4 days in normal hairless mice
followed by topical applications of either 1% Tuhuai extract or
Vehicle to both flanks immediately after each barrier perturbation.
Changes in epidermal proliferation and apoptosis were evaluated by
immunohistochemistry and TUNEL staining. To assess the anti-
inflammatory effects of Tuhuai, both irritant (phorbol ester) and
acute allergic contact dermatitis (oxazolone) models were used.
Whereas topical Tuhuai extract did not alter epidermal proliferation
or induce irritation in normal skin, it both reduced epidermal
hyperplasia in the epidermal hyperproliferative model, and reduced
inflammation in both irritant and allergic contact dermatitis models.
As topical Tuhuai extract exhibits anti-proliferative and anti-
inflammatory properties in a variety of human models of inflammatory
dermatoses, Tuhuai could provide an effective, relatively safe and
inexpensive therapeutic alternative for the treatment of inflammatory
dermatoses, including psoriasis.
PMID: 18341576
I'm not going to run these in google images till later. I can hardly
wait.
----------------------------------------
This one has been around this group previously.
http://www.ncbi.nlm.nih.gov/pubmed/18341666?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Polymorphisms in the PTPN22 region are associated with psoriasis of
early onset.
Smith RL, Warren RB, Eyre S, Ke X, Young HS, Allen M, Strachan D,
McArdle W, Gittins MP, Barker JN, Griffiths CE, Worthington J.
arc Epidemiology Unit, The University of Manchester, Manchester M13
9PT, U.K.
Background Psoriasis, a chronic inflammatory skin disease, affects
approximately 2% of the population worldwide. Although the aetiology
of psoriasis is poorly understood, patients with disease of early
onset (Type I, age of onset </= 40 years) usually have a strong
genetic component to the disease. Objectives The purpose of this study
was to investigate the role of the protein tyrosine phosphatase
nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I
psoriasis. Patients and methods Thirteen single nucleotide
polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in
647 patients with Type I psoriasis and 566 normal controls. Results
The rs2476601 (R620W) SNP, widely associated with other inflammatory
autoimmune diseases, showed no evidence of association with
susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604)
demonstrated significant association with Type I psoriasis and were
subsequently genotyped in a further 253 unrelated patients and 2024
normal controls. rs1217414 and rs3789604 were also significantly
associated with Type I psoriasis in the combined datasets (P = 0.003
and P = 0.0002, respectively); furthermore carriage of both risk
alleles was also significantly associated (P = 0.002). Conclusions
This study demonstrates evidence of association of two SNPs (rs1217414
and rs3789604) in the PTPN22 region with Type I psoriasis, providing
evidence for a role of this gene in Type I psoriasis that is not
conferred by the R620W variant previously associated with a number of
inflammatory diseases.
PMID: 18341666
---------------------------------------
http://www.ncbi.nlm.nih.gov/pubmed/18344883?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Complete Remission of Severe Scleritis and Psoriasis in a Patient With
Active Crohn's Disease Using Modulen IBD as an Exclusive
Immunomodulating Diet.
Triantafillidis JK, Mantzaris G, Stamataki A, Asvestis K, Malgarinos
G, Gikas A.
*Department of Gastroenterology, “Saint Panteleimon” General State
Hospital, Nicea †1st Department of Gastroenterology “Evangelismos”
Hospital Athens ‡Health Center of Salamis, Salamis.
PMID: 18344883
-----------
That was curious.
Modulen from Nestle:
http://www.cwimedical.com/modulen-ibd.html
helps IBD, may help P?
OK. No wonder. It's got TGF-beta from sweet whey. Exactly what's been
helping me for eight years now. No small wonder it helps crohn's
and IBD.
http://groups.google.com/groups/search?qt_s=1&q=TGF-%C3%9F2+psoriasis
and/or
http://groups.google.com/groups/search?q=TGF-beta+psoriasis&qt_s=Search
And checking pubmed for keywords: psoria* TGF-*
Look at the second one, there's a SNP for TFG-beta
----
Thanks to skeats we have a fairly good feel for what she's gone
through over the years.
P and Coeliac Disease being multifactorial genetic disorders.
http://www.medicalnewstoday.com/articles/100294.php
--------------------------------------
CheaP and Easy skin HIGHs..
P skin on the peel?
WhooPs the banana peel.... <g>
http://www.dailyherald.com/story/?id=153661
Banana skin an appealing cure for psoriasis
By Dr. Peter Gott
Q. I have used several of your home remedies with success. The
"drunken raisin" for gout, the soap under the sheets for leg cramps,
castor oil for arthritis and more. My husband thought I had finally
"gone off the deep end" when I went after him with a handful of banana
peels.
We had been using a prescription medication on his psoriasis every day
for more than two years. It has had very little effect. I rubbed the
inside of the banana peels on the affected patches (his head, neck,
face and back) once a day. After three days, the psoriasis had nearly
cleared up (about 90 percent was gone). My husband now uses the peels
once a week to keep his skin clear.
Thank you, from both of us, for passing along all these helpful hints.
<sniP>
---------------------
More from dr. Gott:
http://www.northernnews.ca/ArticleDisplay.aspx?e=951131
...
Because of its similarity to psoriasis, some of my readers have tried
Vicks VapoRub with success. Others have had success rubbing a banana
peel onto the affected area once or twice a day.
<sniP>
---------------------------------------
http://news.biocompare.com/newsstory.asp?id=220010
Caspase-12: MUHC Researcher Finds New Defense Mechanism Against
Intestinal Inflammation
3/13/2008
Source: McGill University Health Centre
The body’s first line of defence against pathogenic bacteria that we
ingest may not be the immune system but rather the cells that line the
intestine. This surprising conclusion is just one facet of a study by
Dr. Maya Saleh, a researcher at the Research institute of the McGill
University Health Centre that will be published in the journal Cell
Host & Microbe on March 12.
This, and the various mechanisms revealed by this discovery, could
lead to important therapeutic innovations, particularly in the
treatment of diarrheal diseases and inflammatory bowel diseases such
as Crohn’s disease.
When pathogenic E. coli bacteria infect the body, they bind to
epithelial cells on the interior wall of the intestine before
injecting infectious material into the cells with a syringe-like
mechanism. This contact triggers a defence reaction within the
epithelial cell called the Nod pathway, which results in alerting the
immune system as well as in the release of antimicrobial peptides
called defensins.
Defensins act as antibiotics: they kill bacteria directly by
puncturing holes in their walls. These peptides also play a role in
activating the immune system itself and tuning the inflammatory
reaction.
“This mechanism expands our idea of immunity: it hinges upon
epithelial cells, not immune cells, early on during infection,” says
Dr. Saleh. “Furthermore, our study demonstrates that this mechanism is
regulated negatively by the Caspase-12 protein, meaning that this
protein limits defensin production. This hampers the elimination of
bacteria, which then trigger an intense inflammatory reaction
manifested by various symptoms including severe diahrrea.”
These fundamental discoveries change our understanding of the immune
defence. They also open new avenues for a deeper understanding and
more targeted treatments of diseases related to intestinal
inflammation, such as diarrheal diseases caused by pathogenic E. coli
or Crohn’s disease.
In the case of diarrhea, intestinal inflammation is caused by a
process similar to the one described above by Dr. Saleh. Treatments
that target Caspase-12 would decrease inflammation by acting on the
source rather than on the symptoms.
Crohn’s disease is the chronic inflammation of the digestive tract,
and its specific causes are unknown. What is known, however, is that
this pathology is linked to a genetic mutation in the Nod pathway.
“This study allows us to consider three possible explanations for
Crohn’s disease: the Nod pathway mutation could induce either a lack
of bacterial “sensing” or a hyperactivation of the immune system
resulting in both cases in excessive inflammation against bacteria
naturally present in the digestive system; it is also possible that
the pathology is caused by an excessive and recurring reaction against
a pathogenic microorganism,” says Dr. Saleh. The debate is now open.
In each of these cases, medication targeting Caspase-12 would decrease
inflammation symptoms by directly attacking the underlying cause.
----------------------------------
Isolagen, Inc. Completes Enrollment In Isolagen Therapy(TM) Phase II/
III Acne
Scar Study
http://www.medicalnewstoday.com/articles/100742.php
Glycotex Completes Enrollment In Phase IIa Study Of Lead Product
Candidate
GLYC-101 For Wound Healing
http://www.medicalnewstoday.com/articles/100575.php
CombinatoRx Drug Candidate CRx-191 Demonstrates Positive Phase 2
Results In
Psoriasis
http://www.medicalnewstoday.com/articles/100566.php
Psoriasis Patients Need To Be Checked For Multiple Concurrent Diseases
http://www.medicalnewstoday.com/articles/100266.php
======================================
More on herbs:
http://www.losangeleschronicle.com/articles/55760
Figwort - Uses and Side Effects
Ricky Hussey
The useful constituents of figwort are derived from the dried flowers
and leaves of Scrophularia nodosa. It contains iridoids, flavonoids,
tannins, and phenolic acids. Iridoid and phenylethanoid glycosides
have also been isolated from the aerial parts of the plant. Two of
these glycosides, harpagoside and harpagide, may have heart-
strengthening and antiinflammatory properties. It's available as dried
herb and root, liquid extract, and tincture.
Reported uses
Figwort is used externally to treat skin conditions, such as eczema
and psoriasis. It may also help heal wounds, ulcers, burns, and
hemorrhoids. In homeopathic medicine, figwort is used to treat
decreased resistance, tonsillitis, and lymph edema. It's used
internally for its mild laxative effect and its mild diuretic and
heart strengthening properties.
Administration
Liquid extract 0:1 preparation in 25% alcohol USP): 2 to 8 ml by mouth
three times a day
Tea (steep 2 to 8 g of dried leaves and stems in 5 oz of boiling water
for 5 to 10 minutes: three times a day
Tincture 1:10 preparation in 45% alcohol USP): 2 to 4 ml by mouth
three times a day.
Hazards
Figwort may contain cardiac glycosides; potential interactions may
occur when given with antiarrhythmics or digoxin. Figwort may increase
blood glucose level and therefore may decrease the effectiveness of
hypoglycemics, such as insulin, metformin, or sulfonylureas.
Administration with other cardiac glycoside containing herbs such as
black hellebore, digitalis leaf, lily-of-the-valley, motherwort,
oleander leaf, pheasant's eye, pleurisy root, or uzara could lead to
increased cardiac effects.
http://www.ncbi.nlm.nih.gov/pubmed/16972093?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Occurrence of iridoid glycosides in in vitro cultures and intact
plants of Scrophularia nodosa L.
Sesterhenn K, Distl M, Wink M.
Institut für Pharmazie und Molekulare Biotechnologie, Universität
Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Shoot, root, and callus cultures of Scrophularia nodosa L.
(Scrophulariaceae) were established and cultivated in vitro. Iridoid
glycosides, such as harpagoside, aucubin, and catalpol were identified
by LC-ESI-MS and their contents determined by HPLC. For comparison
intact plants of S. nodosa were analysed. In shoot cultures slightly
lower amounts of detectable iridoid glycosides (4.36% dry weight) were
determined than in the field grown plants (4.88%). Concentration of
harpagoside was highest in leaves of field plants (1.05%) and in
flowers of in vitro plantlets (1.10%). For aucubin the highest amount
was found in the leaves of in vitro plantlets (1.67%) whereas the
levels of aucubin in the leaves of field plants were remarkably lower.
Catalpol was produced as a trace compound in intact plants and shoot
cultures. Callus and root cultures were apparently not able to
synthesise iridoid glycosides.
PMID: 16972093
85 hits for Scrophularia on pubmed
-------------------
randall... I want to be healed with scrophularia. LOL
manfred
wrote:
> > I will try just someCod Liver Oil, with some vitamin D3 1000IU,
> > tonight to judge the reaction.
> > Cruiser
>
> BTW, I meant with vitamin D3 pills, each 1000IU.
>
> cruiser
Didn't BJ work all this out in his Barney's Formula?? It's going to
take a lot more than 1000IU Vitamin D3 and trying to get it with cod
liver oil will result in too much Vitamin A.
Look at the links at http://www.barneysformula.net/ for info on
dosages.
This is a good presentation. It's in regards to Vitamin D for
prostrate cancer but should hold true for other conditions:
http://nuclearmedicine.stanford.edu/education/grand_rounds/07-08/071120.pdf
cruiser
> On Mar 18, 11:30 am, cruiser <tg.cruis...@northwindwireless.com>
> wrote:
>
> > > I will try just someCod Liver Oil, with some vitamin D3 1000IU,
> > > tonight to judge the reaction.
> > > Cruiser
>
> > BTW, I meant with vitamin D3 pills, each 1000IU.
>
> > cruiser
>
> Didn't BJ work all this out in his Barney's Formula?? It's going to
> take a lot more than 1000IU Vitamin D3 and trying to get it with cod
> liver oil will result in too much Vitamin A.
>
> dosages.
>
> This is a good presentation. It's in regards to Vitamin D for
> prostrate cancer but should hold true for other conditions:
>
Did they work out that D3 in large dosage cures endothelial
dysfuntion?
That should give some idea of the dosing.
In any case, I have been keeping Barney's formula in the back of my
mind, ever since I have been able to tie endothial dysfuntion to
vitamin D3. I know he had a grab bag of things he was taking, with a
moderately high dose of vitamin D.
I might go have a look at what they are doing, exactly.
Perhaps they have it all in hand.
Right now I am trying my own grab bag, with 35800IU or about 900ug D3.
I have found several sources saying that 1250ug per day can be
tolerated.
cruiser
cruiser
When you are wounded, microvasculature is severed, and the circulatory
system fails to pass RBCs to feed isolated tissues. Blood flow is also
inhibited around the immediate wound area. This creates hypoxia, which
stimulates a host of chemical responses, intended to repair existing
vasculature, and tissues, and to grow new cells to do it. The body
also responds to fight off potential infection.
Under hypoxic conditions cells cannot sustain the main cell energy
engine and revert to a more primitive furmentation process that
produces less energy. You get mitochorial dysfunction.
The cells starved for oxygen express eNOS abundantly, but when not
enough oxygen comes there is oxydative stress, due to failure to phase
1 detox. If a cell produces too much NO under hypoxic conditions, this
stimulates apoptosis. The zeta chain turns on arginase, turning off
NO, and turning on the polyamine pathway getting ready to divide, to
help close the wound.
eNOS is left starved for arginine and in the absence of improved
oxygen status eNOS stays overexpressed. The return to normoxia would
turn off the expression of eNOS, or at least normalize it. However,
lacking the return to normoxia, the chemical trigger to turn off eNOS
expression is not present.
HIF1 stimulates VEGF, which causes angiogenesus, to restore blood
supply to wounded tissues.
It is my belief that in psoriasis, this whole chemical cascade of
cytokines, etc. ... are all dependent on hypoxia. They mimmic the
wound heeling process stimulated by hypoxia, when vasculature is
ruptured and/or severed. If hypoxia is cleared, all these other
chemical reactions will go away. Well, that is my belief, anyway.
Consequently, I have no wish to discuss cytokines or other issues. I
see them as unfortunate side reactions, having no bearing on the
primary reactions from which they descend.
I have been single mindedly focused on the issue of identifying and
then characterizing, then seeking treatment, for endothelial
dysfunction, which I feel is at the root of all this.
It took me 2.5 years to find that it even had a name, and then I was
surprised to find that there had been over 20,000 papers published on
the topic. From all of these, I was able to find one that
characterized the whole problem, which unfortunately I can't locate
again, and then I was able to find that a simple supplement cure is
already known.
In that one characterization, it was explained that endothelial
dysfunction, was a failure of the EDHF vasorelaxation pathway,
stimulated by acetylcholine. This becomes a problem when arginase gets
going shutting down the NO vasorelaxation pathway, since hypoxia
becomes sustained.
I immediately realized that I had been trying to correct the nitric
oxide pathway, and that this pathway was responding normally to the
conditions to which it was exposed. The nitric oxide pathway is not
broken. It has been turned off by oxidative stress of the zeta chain,
which starts up arginase. My anitoxidant and detox tampering could get
spotty results at best.
If the EDHF pathway was working everything would eventually normalize
on the nitric oxide pathway, as the extra oxygen would allow detox and
cleanup, relieving oxidative stress on the zeta-chain.
To me that amounts to a cure, just as B1 cures Beri Beri.
Time will tell.
Cruiser
manfred
wrote:
>
,>
> It took me 2.5 years to find that it even had a name, and then I was
> surprised to find that there had been over 20,000 papers published on
> the topic. From all of these, I was able to find one that
> characterized the whole problem, which unfortunately I can't locate
> again, and then I was able to find that a simple supplement cure is
> already known.
>
> In that one characterization, it was explained that endothelial
> dysfunction, was a failure of the EDHF vasorelaxation pathway,
> stimulated by acetylcholine. This becomes a problem when arginase gets
> going shutting down the NO vasorelaxation pathway, since hypoxia
> becomes sustained.
>
>
>
Can you give me more details about the paper you can't find. I would
be glad to aid in the search. Was this "simple supplement cure" in
the same paper?
Meanwhile from http://dissertations.ub.rug.nl/FILES/faculties/medicine/2006/p.ochodnicky/thesis.pdf
Intervention strategies leading to reversal of endothelial dysfunction
in humans
General interventions
Physical activity
Smoking cessation
Lipid-lowering therapy
Glycemic control in diabetes
Pharmaceuticals
Angiotensin converting enzyme inhibitors
Angiotensin receptor blockers
Statins
Peroxisome proliferator-activated receptor-γ activators
Estrogens
Dietary supplements
n-3 fatty acids
Folate
Tetrahydrobiopterin
L-Arginine
Vitamin C
Vitamin E
Dietary flavonoids
randall
wrote:
> Randall,
>
<sniP>
>
> If the EDHF pathway was working everything would eventually normalize
> on the nitric oxide pathway, as the extra oxygen would allow detox and
> cleanup, relieving oxidative stress on the zeta-chain.
>
> To me that amounts to a cure, just as B1 cures Beri Beri.
>
> Time will tell.
>
> Cruiser
OK..
I wonder what banana peels have to do with this pathway?
Have you thought of that?
Now don't laugh. We did wheatgrass juice, coconut cures, ginger,
curcumin topical and oral, green tea, coffee enema's, Oregon grape
topicals,
red wine (oral not topical- lol), etc etc ad nauseum
http://news.google.com/news?qt_s=1&tab=gn&hl=en&q=psoriasis+banana&ie=UTF-8
Could BPF (banana peel factor) interact with EDHF and slow down
rapid oxidation factors from all those cytokines, you'd rather not
discuss?
If so then would not your theory demand temporary occlusion to
achieve net results?
Makes sense to take O2 out of the inflammatory pathway.
Look what happens to the banana once it's peeled.
I wonder if green peels will work better? Higher concentrations
of BPF?
Blocking O2 isn't blocking ALL LIfe..
http://en.wikipedia.org/wiki/Oxygen
While O2 is required for life, what about for the life of a FLAKE?
I breathe I live, my skin breathe's it flakes?
WE could design a banana skin for plaques and shrink the sizes
as they wither on the vine. <w>
---------------------
OT: But important to the psyche
Crap, my team has lost in the first round of the big dance.
March madness is turning bleak.... :(
And now my second pick is gone, but third goes up against a biggie
later today...
My side needs a miracle...
Yikes...
randall... pass the low dose cocktail...banana peel?
JXStern
wrote:
>I wonder what banana peels have to do with this pathway?
Linoleic acid, or whatever it is they put in exorex.
J.
cruiser
> wrote:
>
> Can you give me more details about the paper you can't find. I would
> be glad to aid in the search. Was this "simple supplement cure" in
> the same paper?
>
No, I posted that above.
Here it is again:
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1464-5491.2007.023...
Aims To test whether a single large dose of vitamin D2 can improve
endothelial function in patients with Type 2 diabetes mellitus and
low
serum 25-hydroxyvitamin D levels.
Methods Double-blind, parallel group, placebo-controlled randomized
trial.
###############################################
A single dose of 100 000 IU vitamin D2 or placebo was
administered to patients with Type 2 diabetes over the winter, when
levels of circulating 25-hydroxyvitamin D were likely to be lowest.
###############################################
Patients were enrolled if their baseline 25-hydroxyvitamin D level
was
< 50 nmol/l. Endothelial function and blood pressure were measured
and
fasting blood samples were taken at baseline and 8 weeks after
administration of vitamin D.
Results Forty-nine per cent of subjects screened had 25-
hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed
the study, with a mean age of 64 years and a baseline 25-
hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation
increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to
placebo and significantly improved flow mediated vasodilatation (FMD)
of the brachial artery by 2.3%. The improvement in FMD remained
significant after adjusting for changes in blood pressure. Vitamin D
supplementation significantly decreased systolic blood pressure by 14
mmHg compared with placebo; this did not correlate with change in
FMD.
Conclusions Vitamin D insufficiency is common in patients with Type
2
diabetes during winter in Scotland.
####################################################
A single large dose of oral vitamin D2 improves endothelial function
in patients with Type 2
diabetes and vitamin D insufficiency.
####################################################
--------------------------------------
http://www.endocrine-abstracts.org/ea/0014/ea0014p275.htm
Effect of vitamin D replacement on endothelial function and oxidative
stress in vitamin D deficient subjects
Ozlem Tarcin1, Dilek Yavuz1, Ahmet Toprak2, Ahu Telli3, Meral
Yuksel4,
Dilek Yazici1, Seda Sancak1, Oguzhan Deyneli1, Goncagul Haklar3 &
Sema
Akalin1
1Marmara University Medical School Section of Endocrinology and
Metabolism, Istanbul, Turkey; 2Marmara University Medical School
Department of Internal Medicine, Istanbul, Turkey; 3Marmara
University
Medical School Department of Biochemistry, Istanbul, Turkey; 4Marmara
University Vocational School of Health Related Sciences, Istanbul,
Turkey.
Introduction: Vitamin D (Vit D) receptors have been shown in extra
###########################################################
Discussion: We have shown that vit D deficiency causes endothelial
dysfunction. Vit D replacement led to the improvement on endothelial
function and decreased lipid peroxidation which made us think that
vit
D deficiency could have take part in the pathogenesis of
atherosclerosis.
###########################################################
cruiser
cruiser
> Can you give me more details about the paper you can't find.
The author discussed arginase 1 and arginase II, as well as EDHF and
eNOS, exogenus nitric oxide, nytroglycerin, acetylcholine.
In any case the paper did not alllude to vitamin D as a cure.
I mostly put me on to understanding that the EDHF vasorelaxation
pathway is broken. It comes right out an says that.
That information is also contained below:
> http://www.nature.com/bjp/journal/v127/n3/full/0702581a.html
> The mechanism responsible for blood pressure reduction in
> spontaneously hypertensive rats (SHR) after prolonged cholecalciferol
> treatment was studied.
Rats with high blood pressure were fed vitamin D, and their blood
pressure dropped.
They want to study why..
> Two-week treatment of SHR with 0.125 mg
> cholecalciferol kg-1 body weight per day orally caused significant
> reductions of systolic blood pressure and of the resting perfusion
> pressure of the mesenteric vascular bed at constant flow.
So, the treated rats got lower blood pressure, as expected.
> In addition, the treated animals presented a normalization of the
> maximum vasoconstriction response to noradrenaline and a reduction of
> the maximum effect of the adrenaline concentration-response curves.
> This latter
And their blood vessels were able to constrict better, and they did
not constrict as severly, when stressed.
###################
effect probably was due to recovery of the impaired Ca2+-
> dependent K+ channels coupled to 2-adrenoceptors
###################
We saw previously that vitamin D effects calcium channels "acutely"
meaning a whole bunch, in milliseconds of contact. It causes high
membrane polarization, or hyperpolarization.
> since it was prevented by apamin.
> The treatment with cholecalciferol also normalized the smooth muscle
> cell membrane potential of de-endothelialized mesenteric arteries of
> SHR and their hyperpolarizing responses to 2-adrenergic agonists,
> which were depressed in untreated SHR.
> In mesenteric rings with endothelium, 2-adrenergic agonists caused
> similar hyperpolarizing responses in the SHR and in normotensive
> Wistar (NWR) and Wistar Kyoto (WKY).
Now this is the real center of it all.
I really mean that.
This is the root of the problem. You have to read it carefully and
understnd what they are saying.
#####################
> In non cholecalciferol-treated SHR the hyperpolarizing mediator involved in this effect was NO, while
> in NWR it was the endothelium-derived hyperpolarizing factor (EDHF).
#####################
So in rats with high blood pressure that got no treatment, nitric
oxide was was the primary vasodialtor.
In other words, for rats with endothelial dysfunction nitric oxide is
the main pathway for vasorelaxation.
For normal untreated control rats, the vasorelaxation pathway was
EDHF, not nitric oxide. So, EDHF is the noramlly the primary
vasodilator, not nitric oxide. Nitric Oxide is secondary.
This really characterizes endothelial dysfunction.
The EDHF pathway initiated by acetylcholine stimulation is not
functioning, and sustained hypoxia results, when the Nitric Oxide
pathway is also turned off by oxidative stress to the zeta-chain,
which cause arginase expression.
That is the very heart of the probelm.
#####################
> After cholecalciferol treatment, the hyperpolarization induced by 2-
> adrenergic agonists in SHR smooth muscle cells was mediated by EDHF,
> as in NWR.
######################
So, the other group. The rats with high blood pressure who were lucky
enough to get the vitamin D treatment, also showed the normal response
of vasorelaxation triggered by EDHF, not nitric oxide. They vitamin D
fixed them.
######################
> Our results indicate that the hypotensive effect of cholecalciferol in
> the SHR is probably due to the normalization of vascular reactivity,
> by restoring the functioning of apamin- and ATP-sensitive K+ channels
> located in the vascular smooth muscle cell membrane, which are
> impaired in the SHR
######################
vitamin D restores the the functioning of K+ channles located in
vascular smooth muscle cell membranes, that are impaired in
hypertensive rats.
http://www.ncbi.nlm.nih.gov/pubmed/9389744
##################################################
The results showed that (a) the contribution of EDHF to endothelium-
dependent relaxations is significantly larger in microvessels than in
large arteries;
##################################################
cruiser
cruiser
wrote:
Manfred,
Just to explain a bit more.
Nitric Oxide is not desirable in stressed tissues, because NO becomes
a signal for apoptosis - cell death, by suicide..
Nitric Oxide for vaosdilation is shut down by arginase, which also
starts up the polyamine pathway, which swells the cells, with
polyamines, in preparation for cell division. Look at a slide of
psoriatic cells sometime. You can see how the cells look bloated, and
stressed.
I think this is normal cell chemistry, in response to the conditions.
I don't think this is broken. I think it is pointless to try to fix
it. I have tried for a long time and can atest to the lack of results.
EDHF is supposed to provide vasorelaxation in microvasculature,
because " the contribution of EDHF to endothelium-
dependent relaxations is significantly larger in microvessels than in
large arteries; "
If EDHF is not working, then sustained hypoxia sets in. The cells are
then in a state of constantly thinking that they are involved in wound
repair.
This could be the cause of psoriasis, arthritic changes, vascular
plaques, and brain lesions.
In particular, the thing that set me down this path in the first
place, was that glutamate and aspartate react with the NMDA receptors
and cause excessive release of acetylcholine. This same excessive
release of acetylcholine is seen in stroke.
Since acetylcholine initiates the EDFH pathway, one would expect that
vasorelaxation would provide oxygen relief, but it seems not, since
the excessive acetylcholine is chronic and problematic.
This makes sense now. The EDHF pathway is broken, and acetylcholine is
overexpressed, because the off homeostasis mechanism - normoxia - is
not satisfied.
This was a clue to the problem that I failed to pick up on. It was
only just very recently that I learned of the separate EDHF
vasorelaxation pathway. Until then, I thought it was all nitric oxide.
I'm an amateur.
Cruiser
cruiser
> This is a good presentation. It's in regards to Vitamin D for
> prostrate cancer but should hold true for other conditions:
>
You know they don't mention anything about the involvement of vitamin
D in endothelial calcium influx for vasodilation.
Nothing ever does.
I have only read about calcium, bones, and vitamin D.
Who'd a thunk?
cruiser
manfred
Inflammation-induced endothelial dysfunction involves reduced nitric
oxide bioavailability and increased oxidant stress
Alternative Medicine Review, Dec, 2004
"...Inflammation causes widespread endothelial dysfunction, reduces
vascular NO bioavailability and increases oxidative stress. These
actions are partially reversible with local anti-oxidants. These
findings suggest a role for reactive oxygen species in inflammation-
induced endothelial dysfunction." http://findarticles.com/p/articles/mi_m0FDN/is_4_9/ai_n9479463
"Is tumour necrosis factor- (TNF-) the key mediator of endothelial
dysfunction?
...several lines of evidence suggest that the pro-inflammatory
cytokine TNF- plays a key role in inducing endothelial dysfunction.
First, in clinically stable heart transplant patients a strong
positive relation between plasma TNF- levels and the vascular response
to acetylcholine has been documented [29]. Second, Bhagat and Vallance
[14] have shown that whereas infusion of TNF- alone impaired
endothelial function in healthy subjects, infusion of IL-6 did not. In
addition, another study has shown that administration of TNF-
depresses endothelium-dependent relaxation in vivo [30]. Finally, cell
culture experiments have shown that TNF- reduces the half-life of mRNA
encoding for endothelial NO synthase [31]. A key role for TNF- in
mediating endothelial dysfunction is of interest not only because
markedly elevated serum levels of TNF- have been documented in ESRD
patients [32] but also because we now have access to targeted anti-TNF
therapies, such as etanercept. Thus, new effective treatment
strategies may emerge for ESRD patients in the future. The exact
mechanism(s) by which various pro-inflammatory mediators, such as
TNF-, cause endothelial dysfunction are not yet known. However,
Kessler et al. [33] have shown that pro-inflammatory mediators induce
NO synthase expression in cultures of endothelial cells and decreased
expression of cytochrome P450 enzymes, both of which are probable
candidates for synthesis of endothelium-derived hyperpolarizing factor
(EDHF)." http://ndt.oxfordjournals.org/cgi/content/full/16/10/1968
"Various infections cause endothelial dysfunction
The cause of inflammation in ESRD patients may be multifactorial but
it is probable that various chronic infectious processes contribute.
Recent evidence suggests the participation of chronic Chlamydia
pneumonia infection in the pathogenesis of atherosclerosis in both the
general population [21] and ESRD patients [22,23]. It is, therefore,
of interest that Liuba et al. [24] have shown that repeated C.
pneumonia infections impairs endothelial function in apolipoprotein E-
knockout mice. Importantly, recent evidence suggests that also other
persistent infections may contribute to endothelial dysfunction in
humans. In a preliminary study Prasad et al. [25] have shown that
prior infection with cytomegalovirus, hepatitis A virus, herpes
simplex virus type 1, C. pneumonia and Helicobacter pylori are risk
factors for coronary endothelial dysfunction. Moreover, in HIV
infection, dysfunctional or injured endothelial cells potentiate
tissue injury and inflammation and accelerate the development of CVD
[26]. Finally, Channon et al. [27] have shown that recombinant
adenovirus triggers an early inflammatory response and that it is the
inflammatory response that causes functional endothelial injury"
http://ndt.oxfordjournals.org/cgi/content/full/16/10/1968
"Anti-inflammatory treatment strategies improve endothelial function
Whereas a number of different treatment strategies (Table 2), such as
ACE-inhibitors, statins, antioxidants, folic acid and nutritional
supplements (L-arginine) have been shown to improve endothelial
function in various non-renal patient groups, data on the effects of
various anti-inflammatory treatment strategies on endothelial function
are scarce. Bhagat and Vallance [14] showed that administration of
hydrocortisone (100 mg) and high-dose aspirin (1000 mg) prevented
cytokine induced endothelial dysfunction in healthy controls, whereas
low-dose aspirin (75 mg) did not. Further evidence for a positive
effect of anti-inflammatory treatment of endothelial function can be
derived from a recent study in which it was shown that treatment of
primary systemic vasculitis with steroids and/or cyclophosphamide was
associated with a normalization of endothelial function [34]. "
http://ndt.oxfordjournals.org/cgi/content/full/16/10/1968