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Prolactin, Cholesterol & Vit D questions

Postby Wonderfulworld » Fri Sep 03, 2010 3:15 am

Just wondering if any of you who are interested in an Endocrine/Vitamin /CCSVI angle on MS would have any feedback?
My GP ran some bloods to investigate some non-MS problems I am having.

Prolactin - above normal
Cholesterol - above normal 5.3nmol

I was doing some reading about these as the GP has yet to ring me to advise on them.

I have found some research on Pubmed that suggests Prolactin is a negative thing for PWMS and is raised in both men and women, particularly that it is raised during a relapse. Other medical information states Prolactin is needed to create Oligodendrocytes (precursors to Myelin) so meaning a raised Prolactin level may be the body trying to repair your myelin?
Even more intriugingly I found an article that said Prolactin is circulated in the body from the pituitary gland to the parathyroid VIA small venous channels and if there is a blockage in these it can cause elevation of Prolaction - perhaps a CCSVI link?

Has anyone on the board done any in-depth digging on the role of Prolactin in MS?

Then on to the Cholesterol levels - it is needed to metabolise Vitamin D3, so I'm starting to wonder if it's shot up above normal to cope with the 4000IU of D3 I'm taking?
I used to do a once-fortnightly niacin-flush but hadn't done it so often recently, so I am going to reinstate it as it lowers LDL cholesterol. And widens veins albeit temporarily.

(Incidentally my Vit D3 is now 70nmol/L but I'm working on getting it to 100nmol/L and I've been given neuro's 'permission' to continue with 4000IU per day along with Cal/Mag/Zinc. My thyroid and glucose tolerance are both normal).
~~~~~~~~~~~~~~~
Concussus Resurgo
~~~~~~~~~~~~~~~
RR-MS dx 1998 and Coeliac dx 2003
~~~~~~~~~~~~~~~
Tecfidera, Cymbalta, Baclofen.
EPO, Fish Oils, Vitamin D3 2000 IU, Magnesium, Multivitamin/mineral, Co-Enzyme Q10, Probiotics, Milk Thistle, Melatonin.
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Postby jimmylegs » Fri Sep 03, 2010 5:11 am

heya :) well i went looking at pituitary and deficiency and the first results were talking about zinc so i just went with that. however quickly just switched over to prolactin levels and zinc. here is the review:

http://jn.nutrition.org/cgi/content/abstract/134/6/1314
Maternal Zinc Deficiency Raises Plasma Prolactin Levels in Lactating Rats

http://www.ncbi.nlm.nih.gov/pubmed/8562282
Endocrine interaction between zinc and prolactin. An interpretative review.
Zn2+ can inhibit PRL secretion within a range of physiologically and pharmacologically relevant concentrations


http://www.ncbi.nlm.nih.gov/pubmed/6697238
Zinc acutely, selectively and reversibly inhibits pituitary prolactin secretion

http://jcem.endojournals.org/cgi/conten ... t/68/1/215
Zinc Does Not Acutely Suppress Prolactin in Normal or Hyperprolactinemic Women

this last one.. i don't have full text access but from the abstract it appears that they were looking for a prolactin response after a single dose??? whereas the pregnant rat study was ongoing starting before pregnancy and continuing through out until after lactation. also, the levels achieved were startlingly high considering healthy controls levels are 18.2 umol/L. wonder what their zinc levels were before they started the zinc study?

http://www.ncbi.nlm.nih.gov/pubmed/6810775
Zinc, Prolactin, Gonadotropins, and Androgen Levels in Uremic Men
This study correlates plasma levels of Zinc (Zn) and some pituitary and testicular hormones in 20 uremic men (aged 17–58 years) on a weekly peritoneal dialysis program. Patients were compared to 12 healthy male volunteers (aged 28–40 years). In uremic men, plasma andros-tenedione (A) was elevated, while testosterone (T), dihydrotestosterone (DHT), and Zn were low. On a group basis, plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) were normal while prolactin was increased.


http://linkinghub.elsevier.com/retrieve ... 3685906300
EFFECT OF ZINC SUPPLEMENTATION ON HYPERPROLACTINAEMIA IN URAEMIC MEN
Zinc and prolactin levels were measured in 32 male haemodialysis patients; 12 were receiving 50 mg zinc per day as zinc acetate and 20 were not. Zinc-treated patients had significantly higher plasma zinc levels (134±10 μg/dl v 88±2 μg/dl) and lower serum prolactin levels (11±4 ng/ml v 29±7 ng/ml) than untreated patients. Plasma zinc and serum prolactin were inversely related in zinc-treated and untreated patients (r = -0·79, p<0·001).


okay that's better, a longer term supplementation effort... now for the units conversion on the zinc.. Zinc µg/dL 0.153 µmoI/L ... all right the supplemented group got to 20.5 umol/L, a little higher than the average healthy control of 18.2, but still pretty close.

i looked for some more recent abstracts and ran across this tangential bit of info:
http://clincancerres.aacrjournals.org/c ... 9.abstract
Zinc inhibits nuclear factor-κB activation and sensitizes prostate cancer cells to cytotoxic agents

that brought me back to earlier discussions here about NF-κB and MS relapses. so to refresh, i did a quick search on MS and NF-κB, and the hits are talking about glatiramer acetate. Copaxone suppresses NF-κB too. interesting.

at the end of the day, i think it's a good thing you're on zinc. might be helpful to test your levels now and then :)

on to cholesterol:
http://www.ncbi.nlm.nih.gov/pubmed/3295705
Serum zinc and copper in hypercholesterolemia
The serum copper concentration was elevated, serum zinc concentration and zinc/copper ratio were decreased in the hypercholesterolemic group (cholesterol greater than 7.7 mmol/l).


that's all for now, gotta split :)

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Postby CureOrBust » Fri Sep 03, 2010 6:19 am

A thread specifically on Prolactin: http://www.thisisms.com/ftopicp-24418.html#24418
Its also in Phase I on Dignans pipeline: http://www.thisisms.com/ftopicp-55819.html#55819
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Vitamin D - health perspectives & deficiencies

Postby MSUK » Tue Sep 07, 2010 11:40 pm

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Abstract
Vitamin D, the sunshine vitamin, has been important not only for the evolution of a healthy calcified vertebrate skeleton but it also evolved into a hormone that has a wide diversity of biologic effects.
During exposure to sunlight the ultraviolet B radiation converts 7-dehydrocholesterol to previtamin D(3) which in turn rapidly isomerizes to vitamin D(3)....

............... It is estimated that 1 billion people worldwide are vitamin D deficient or insufficient. Correcting and preventing this deficiency could have an enormous impact on reducing health costs worldwide..............Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334
MS-UK - http://www.ms-uk.org/
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Postby Wonderfulworld » Thu Sep 16, 2010 2:53 am

I second what JL says. My D3 levels only started moving up to normal when I took zinc/cal/mag too.
I have to take 4000IU per day to keep my levels normal. Any less and they drop below normal. Living in Ireland I am pale, blue-eyed, dark hair but actually have sallow skin that tans easily. I am now avoiding the sun because it's aged my skin badly and I'm trying to keep D3 levels normal through supplements.

For those of you who are finding D3 or Iron keeps dropping it might be also worth your while finding out if you are coeliac as that would cause absorbtion problems. Your GP can run a screening blood test for you to rule it out. I never understood why I had so many symptoms of vitamin/mineral deficiencies (brittle nails, sore tongue, angular chelitis) in the past despite a good diet and supplements. My health only improved after finding out I was a coeliac and going gluten-free for life.

Edited for spelling.
~~~~~~~~~~~~~~~
Concussus Resurgo
~~~~~~~~~~~~~~~
RR-MS dx 1998 and Coeliac dx 2003
~~~~~~~~~~~~~~~
Tecfidera, Cymbalta, Baclofen.
EPO, Fish Oils, Vitamin D3 2000 IU, Magnesium, Multivitamin/mineral, Co-Enzyme Q10, Probiotics, Milk Thistle, Melatonin.
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Postby jimmylegs » Thu Sep 16, 2010 5:07 am

merlyn now that i know about your recalcitrant zinc deficiency from the phlebotomy thread, i re-state my earlier suggestion of investigating your protein status via a prealbumin test. or at least an albumin test. if you don't have enough protein in your system, supplementing zinc won't do any good!
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Scottish warning over vitamin D levels

Postby MSUK » Mon Sep 20, 2010 4:47 am

Image

New leaflets are to be handed out urging people to make sure they get enough vitamin D.

Doctors are concerned people in Scotland are not getting enough of the vitamin from sunlight and are not topping up their levels with a healthy diet.

There is increasing evidence that a lack of vitamin D could be linked to cancer and multiple sclerosis.
Doctors are also concerned about a rise in the bone disease rickets.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334
MS-UK - http://www.ms-uk.org/
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Vitamin D could be tested as MS aid in Scotland

Postby MSUK » Wed Sep 22, 2010 2:05 am

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Vitamin D supplements should be introduced in Scotland to see if they can help combat multiple sclerosis (MS), an expert has said.

Professor George Ebers, from Oxford University, made the suggestion at a one-day summit examining the possible link between MS and vitamin D deficiency.
The vitamin is naturally created in the body by exposure to the sun but in Scotland there is only enough sunlight of the necessary UVB wavelength for about half the year.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334
MS-UK - http://www.ms-uk.org/
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Postby jimmylegs » Sun Sep 26, 2010 5:37 pm

Thank you for the opportunity to provide input on proposal 10-HLTC032.

I have copied the proposal text below and have inserted my comments and relevant research citations and quotes throughout, separated by asterisks like so: *****


ONTARIO PROPOSAL: Funding of Vitamin D Testing Based on Clinical Evidence

Ministry: Ministry of Health and Long-Term Care
Regulation Number(s): 552

Bill or Act: Health Insurance Act
Summary of Proposal: The Ministry of Health and Long-term Care (MOHTLC) will be improving the quality and value of health care based on the best medical evidence available by providing Vitamin D testing as an insured service to Ontarians with the following conditions: Osteoporosis, Rickets, Osteopenia, Malabsorption Syndromes and Renal Disease; or
Ontarians who are on medications that affect Vitamin D metabolism. This proposal is aligned with the Excellent Care for All Act that will improve quality, value and promote evidence-based health care. The Act will ensure that future investments get results and improve health while preserving the health care system for future generations.

*****

MY COMMENTS: Vitamin D testing as an insured service must be provided to Multiple Sclerosis patients. Patients must be able to determine whether their dietary and supplementation regimens are successfully achieving levels above 100 nmol/L, without exceeding 250 nmol/L.

Some cases of Vitamin D3 deficiency or insufficiency are refractory and without testing it is impossible to know whether following a regimen is making the required difference in serum levels.

At the upper end of the scale, concerns regarding Vitamin D3 toxicity issues (such as hypercalcaemia) indicate that patients using therapeutic intakes of Vitamin D3 must be monitored.

*****

On the relevance of Vitamin D3 to MS:

STUDY: Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis
Kassandra L. Munger, MSc; Lynn I. Levin, PhD, MPH; Bruce W. Hollis, PhD; Noel S. Howard, MD; Alberto Ascherio, MD, DrPH
JAMA. 2006;296:2832-2838.
http://www.ncbi.nlm.nih.gov/pubmed/17179460

"...the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L..." "The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis."

STUDY: Vitamin D intake and incidence of multiple sclerosis
K. L. Munger, MSc, S. M. Zhang, MD ScD, E. O’Reilly, MSc, M. A. Hernán, MD DrPH, M. J. Olek, DO, W. C. Willett, MD DrPH and A. Ascherio, MD DrPH
NEUROLOGY 2004;62:60-65
http://www.ncbi.nlm.nih.gov/pubmed/14718698

"The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS;"

*****

ONTARIO PROPOSAL: Studies of the general population suggest a relatively low prevalence, approximately 5%, of Canadians had Vitamin D deficiency, and between 10% and 25% had low Vitamin D levels. Since 2005, reports have promoted Vitamin D testing and have contributed to the sharp increase in demand for Vitamin D testing in Ontario. Annual billing data shows that Vitamin D testing volumes increased 2500% from 2004/2005 to 2009/2010. If this trend continues, billings could reach up to $155M by 2011/12, for both medically necessary and unwarranted tests.

*****

MY COMMENTS: I would be interested to see which studies are referred to above. How do these terms line up with the following proposed classification?

*****

STUDY: Secondary hyperparathyroidism in the elderly: means to defining hypovitaminosis D.
McKenna MJ, Freaney R.
Osteoporos Int. 1998;8 Suppl 2:S3-6.
http://www.ncbi.nlm.nih.gov/pubmed/10197175

in

STUDY: Vitamin D deficiency: a neglected aspect of disturbed calcium metabolism in renal failure
Jorge B. Cannata‐Andía and Carlos Gómez Alonso
http://ndt.oxfordjournals.org/content/1 ... ull#ref-16

"The following classification has been proposed:
(i) Hypovitaminosis D: concentrations between 20 and 40 ng/ml (50 and 100 nmol/l).

(ii) Vitamin D insufficiency: plasma concentration between 10 and 20 ng/ml (25-50 nmol/l).

(iii) Vitamin D deficiency: 25(OH)D concentrations <10 ng/ml (25 nmol/l)."

*****

MY COMMENTS: Does the literature review include any studies which suggest that levels below 100 nmol/L may actually indicate deficiency, as opposed to hypovitaminosis D?

*****

STUDY: Lessons for nutritional science from vitamin D.
Heaney RP.
Am J Clin Nutr. 1999 May;69(5):825-6.
http://www.ncbi.nlm.nih.gov/pubmed/10232617

"Vieth makes a point that should help us with the needed mental adjustment: individuals exposed to the sun for much of the year in lower latitudes always have blood 25(OH)D concentrations values >100 nmol/L. So, if the true lower limit of the acceptable normal range is, in fact, 100 nmol/L, it could hardly be considered 'high'."

*****

ONTARIO PROPOSAL: Vitamin D testing is currently insured for all Ontarians under OHIP. However, there is no evidence that routine testing of Vitamin D levels encourages adherence to Health Canada’s guidelines. At present, the most efficient way to ensure adequate Vitamin D levels in healthy individuals is to promote Health Canada’s guidelines for maintaining sufficient levels.

*****

MY COMMENTS: By "no evidence", do you mean that no one has investigated testing and adherence yet? If there is a study on this matter which concludes testing does not affect adherence, I would be pleased to read it if you would be so good as to refer me.

In any case, Health Canada's guidelines are insufficient to guarantee serum levels of vitamin D3 at levels associated with least risk of Multiple Sclerosis.
http://www.hc-sc.gc.ca/fn-an/nutrition/ ... bl-eng.php
Health Canada AI = 200 - 600 IU/d, UL 2000 IU/d

The study cited below shows that on 1000 IU/d, the absolute best a patient can do is get up to the cutoff. Even on 4000 IU per day some patients only achieved serum levels between 69 and 100 nmol/L.

This study also demonstrates the wild variability in patients’ serum levels when supplementing identical levels on a daily basis.

[Personal anecdote: my dose-response to one vitamin D3 regimen (a booster, not a maintenance regimen) resulted first in a serum increase of approx 70 nmol/L, and the next time in a serum increase of approx 170 nmol/L, which put me well over 250 nmol/L, the cutoff above which hypercalcemia may occur. Without testing I would have had no idea.]

Vitamin D3 testing is required to ensure that a patient’s daily regimen is successfully getting their serum level above the cutoff, and in some cases it is required to ensure they remain below the upper end of the safe range.

*****

STUDY: Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level
Reinhold Vieth, Pak-Cheung R Chan and Gordon D MacFarlane
American Journal of Clinical Nutrition, Vol. 73, No. 2, 288-294, February 2001
http://www.ncbi.nlm.nih.gov/pubmed/11157326

"The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg (1000 and 4000 IU) vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively."

STUDY: A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis.
Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D'Souza C, Ursell M, O'Connor P.
Neurology. 2010 Jun 8;74(23):1852-9. Epub 2010 Apr 28.
http://www.ncbi.nlm.nih.gov/pubmed/20427749

"Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.
CONCLUSIONS: High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects."

STUDY: Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis.
Simpson S Jr et al
Ann Neurol. 2010 Aug;68(2):193-203.
http://www.ncbi.nlm.nih.gov/pubmed/20695012

"A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied... Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis... higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50nmol/l could halve the hazard of a relapse."

*****

ONTARIO PROPOSAL: In June, Ontario’s Health Technology Advisory Committee (OHTAC) concluded that the routine use of Vitamin D testing could not be justified based on current evidence.

OHTAC’s membership consists of a minimum of 12 health experts, including representatives of the Ontario Medical Association and the Ontario Hospital Association.

The proposed amendment seeks to ensure that the testing provided is based on the best medical evidence, increase value for the health care system by eliminating testing that is not deemed medically necessary and promote quality and sustainability by helping to ensure that the health care system is there for future generations.

The Ministry will continue to regulate Vitamin D testing in accordance with the principle of evidence-based healthcare, and it will seek updates as required to incorporate new medical evidence. Testing would continue to be accessible as an uninsured service to Ontarians who do not meet the medical criteria, but who would still like to pay for testing.

*****

MY COMMENTS: The study cited below suggests that Vitamin D3 status should be measured for ALL patients on an annual basis. Based on all the studies provided in this submission, it is my view that at the very least, Ontario's Multiple Sclerosis sufferers must be added to the list of patients who qualify for OHIP coverage of vitamin D3 testing.

I suggest that in the long term, insured testing of vitamin D3 status will reduce spending on tests such as MRI, lumbar puncture, &c for MS patients, and who knows how many tests for the other conditions listed.

*****

STUDY: The Vitamin D Epidemic and its Health Consequences
Michael F. Holick
J. Nutr. 135:2739S-2748S, November 2005
http://jn.nutrition.org/cgi/content/abs ... 5/11/2739S

"There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one’s vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination."

*****

MY COMMENTS: Thank you again for the opportunity to provide input into this process.

I would be pleased to submit additional literature review and commentary on this proposal, if further evidence is needed to support coverage for vitamin D3 testing for Ontario’s MS patients.
Last edited by jimmylegs on Mon Sep 27, 2010 2:05 pm, edited 2 times in total.
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Re: Ontario health insurance curbs vit d testing

Postby NHE » Mon Sep 27, 2010 12:25 am

Hi Jimmylegs,
I think that this paper ties MS and vitamin D pretty well together. I may have missed it, but did you include this in your letter?

http://www.thisisms.com/ftopicp-128403.html#128403

In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50nmol/l could halve the hazard of a relapse.


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Postby jimmylegs » Mon Sep 27, 2010 4:42 am

thanks for that NHE i'll add it in. i threw the above together pretty fast but am having trouble submitting online - i'll add it in :) thx
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Vitamin D3 rocks -- a study shows 42% reduction in relapses

Postby Rebecca » Sun Oct 10, 2010 2:50 pm

A study from South Africa actually showed that 14,000 IU per day can cut the relapse rate by 42%. This beats the MS drugs.

I love vitamin D3.
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Postby Frank » Sun Oct 10, 2010 3:31 pm

Hi Rebecca, could you please link to a source for the study in South Africa that you mentioned?

Thanks!
--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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Low vitamin D levels linked to depression

Postby MSUK » Mon Oct 11, 2010 1:42 am

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Vitamin D status in patients with MS is negatively correlated with depression, but not with fatigue.

Abstract
Background -  Depressive symptoms and fatigue are frequent and disabling symptoms of multiple sclerosis (MS). Depression and fatigue have been associated with a poor vitamin D status, and a poor vitamin D status is often found in MS....Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1334
MS-UK - http://www.ms-uk.org/
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Low vitamin D levels increases risk of Paediatric MS

Postby MSUK » Sat Oct 16, 2010 11:46 am

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Low serum vitamin D at the time of a first demyelinating event increases the risk of subsequent multiple sclerosis (MS) in children, according to a new study.

Of 208 children under age 16 who experienced an acute demyelinating episode, 41 subsequently received a diagnosis of MS an average of eight months following their first symptom. Those with MS had an average serum vitamin D level of 52 nmol/L, versus 66 nmol/L for those remaining without an MS diagnosis, according to Heather Hanwell, MSc, a PhD candidate in the Department of Nutritional Science at the University of Toronto.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/1408
MS-UK - http://www.ms-uk.org/
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