On Oct 29, 6:43 am, ironjustice <***@aol.com> wrote:
"Hydroxychloroquine's iron-binding ability"
Antimalarial drug prevents diabetes in arthritis patients <<
"I've been taking Salsalate / Disalcid for 12 years now (1250 mg 4x
day) "
http://tinyurl.com/6jtfyn
It should be no surprise the aspirin derived arthritis treating iron-
binding drug Salsalate / Disalcid ALSO have been found to be
effective
in .. diabetes.
The same drugs they use in arthritis is effective in diabetes.
So arthritis iron-binding drugs treat diabetes and diabetes iron-
binding drugs treat arthritis.
I wonder if one might consider ..iron .. as a possible factor in BOTH
diabetes and arthritis .. ?
"This had been found nearly 150 years but had been forgotten or
ignored."
"A chelate theory for aspirin-like drugs."
Anti Inflammatory Medication May Treat Type 2 Diabetes
Article Date: 22 May 2008 - 3:00 PDT
Researchers at the Joslin Diabetes Center who reported earlier this
year that an inexpensive, non-steroidal anti-inflammatory drug called
salsalate might prevent type 2 diabetes are now reporting that the
drug may also be beneficial in the treatment of the disease.
The paper, which appears in the May 2008 issue of the journal
Clinical
and Translational Science (CTS), reports on three proof-of-concept
studies that demonstrate that salsalate, which has been used for
decades to treat arthritis, may benefit patients with type 2 diabetes
by lowering blood sugar and reducing inflammation.
"These are the first studies showing that potentially safe and
tolerable doses of salsalate lower blood sugars and have other
favorable effects in patients with type 2 diabetes," notes Allison B.
Goldfine, M.D., Director of Clinical Research at Joslin and Associate
Professor at Harvard Medical School, and senior author of the report.
Goldfine was also the lead researcher for an earlier study, published
in the February issue of Diabetes Care, which demonstrated that
salsalate may prevent type 2 diabetes by lowering blood glucose and
reducing inflammation.
Together, these four proof-of-concept studies have led to three
large,
ongoing multi-center clinical trials that seek to confirm the benefit
of targeting inflammation using salsalate to lower glucose in
patients
with type 2 diabetes or who are at risk for diabetes, or to reduce
atherosclerosis in patients with coronary artery disease.
The clinical studies are a direct extension of the findings of study
co-author and collaborator Steven Shoelson, M.D., Ph.D., Helen and
Morton Adler Chair, Head of the Section of Cellular and Molecular
Physiology at Joslin, and Professor at Harvard Medical School. Dr.
Shoelson studies the molecular pathogenesis of type 2 diabetes and
the
role of obesity in promoting diabetes and other metabolic conditions,
including atherosclerosis.
It had originally been noted nearly 150 years ago that salicylates
could lower blood glucose levels, but this had either been forgotten
or ignored. Dr. Shoelson's laboratory used this as clue to probe
potential reasons why obesity promotes disease. They found that the
inflammatory pathway regulated by NF-kB is activated in animals with
obesity and diabetes. They went on to demonstrate that this pathway
could be inhibited using salicylates, thus showing that the effects
of
obesity are mediated through inflammation. This was not an accepted
concept at the time, and is still debated in field.
Studies in animals showed that high doses of salicylates, including
aspirin, could be effective, but since these could not be used safely
in patients due to the risk of stomach upset and bleeding the
researchers considered alternative drugs. Together, Drs. Goldfine and
Shoelson opted to study salsalate, which is a salicylate similar to
aspirin but that does not cause stomach upset or bleeding.
Shoelson notes that the studies now being reported in CTS provide a
'smoking gun' new evidence that incriminates inflammation as a major
pathogenic mediator in type 2 diabetes as well as a potentially safe
new way to treat the disease.
"It is rare to see basic discoveries move from bench to bedside so
quickly. This was fueled by at least two things, first the ready
availability of a safe drug, and second the environment at the Joslin
Diabetes Center which is ideally suited to rapid advancements in
clinical discovery," he said.
Goldfine further opines, "much of the pharmacokinetic and long-term
safety data for salsalate is already established, so clinical studies
could move forward rapidly."
"Our findings are potentially very exciting because we show that a
medication that treats inflammation may also treat diabetes and
related medical conditions," said Goldfine. "If we can show in the
larger clinical trials now underway that it is safe and effective, it
means salsalate may be a new way to treat diabetes."
In the paper out today, two of the studies involved small numbers of
patients with type 2 diabetes. One tested salsalate on seven subjects
at a dose of 4.5 grams per day, while the other used 3 grams per day
on nine subjects. Patients in both groups showed benefits such as
reductions in blood sugar between 10 and 20 percent, but improvements
were greatest in the group taking the higher dose. Glucose
utilization
also improved in both groups, although those taking the higher dose
showed a 50 percent improvement, compared to 15 percent for those on
the lower dose. The studies ran for two weeks each.
Impressive reductions were also seen in circulating levels of
triglycerides and free fatty acids, particularly at the higher dose.
This is important because patients with diabetes often have elevated
lipid levels that potentially contribute to complications of type 2
diabetes.
The third study, a double blind, placebo-controlled trial that ran
for
four weeks, involved eight patients on the drug and nine on placebo.
Study participants on the drug showed improvements similar to those
reported in the patients in the other two studies analyzed.
In an accompanying commentary, Barry J. Goldstein, M.D., of the
Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson
Medical College, wrote: "The testing of a commonly used class of
drugs, with a well-known safety profile, offers an exciting
translational approach that promises to help in the management of
glycemia in type 2 diabetes."
He noted: "A world-wide epidemic of type 2 diabetes is underway that
shows no signs of remitting in the next several years. In order to
address the basic therapeutic needs of these millions of patients,
additional treatment options will need to be made available,
especially to have some hope of getting the majority of patients to
accepted glucose treatment goals."
The studies were funded by grants from the National Institutes of
Health; fellowships from the William Randolph Hearst Foundation and
American Diabetes Association; and the Helen and Morton Adler Chair
at
Joslin Diabetes Center.
Other researchers participating included Robert Silver, Elizabeth
Tatro and Jongsoon Lee at Joslin; Waleed Aldahi of Mubarik Alkabeer
University Hospital, Kuwait; and Dongsheng Cai of the University of
Wisconsin.
Salsalate Clinical Trials
Dr. Goldfine is the principal investigator of a study that targets
inflammation using salsalate in patients with coronary artery disease
and metabolic syndrome. The study, called Targeting INflammation
using
SALsalate or Lifestyle intervention in the Metabolic Syndrome and
Cardiovascular Disease (TINSAL-CVD), is funded by The National Heart,
Lung and Blood Institute and is currently enrolling patients. It will
look at the effects of lifestyle intervention (diet, exercise and
omega-3 fatty acid supplement) or salsalate compared to placebo to
reduce progression or promote regression of hard and soft coronary
artery calcification as assessed by multi-detector CT angiography
(MDCTA), a relatively new method to image the coronary arteries.
Patients are randomized to lifestyle, salsalate or placebo with
images
of the coronary arteries at baseline and after 30 months of
intervention. Dr. Shoelson is co-PI on the salsalate arm of the
trial,
while study collaborators Dr. Ernest Schaefer of The Jean Mayer USDA
Human Nutrition Center on Aging at Tufts University and Dr. Francine
Welty of Beth Israel Deaconess Medical Center (BIDMC) are running the
lifestyle intervention arm; Dr. Melvin Clouse of BIDMC is leading the
imaging core.
A second study called Targeting Inflammation using SALsalate in Type
2
Diabetes (TINSAL-T2D) headed by Drs. Goldfine and Shoelson is using
salsalate in patients with type 2 diabetes to target inflammation and
thus lower blood glucose. This study is ongoing and is funded by the
National Institute of Diabetes and Digestive and Kidney Diseases.
Another study led by Dr. Goldfine and Dr. Peter Reaven of the Carl T.
Hayden VA Medical Center in Phoenix targets inflammation using
salsalate in patients with impaired glucose tolerance in order to
improve insulin sensitivity. This study, called TINSAL-IGT, is
ongoing
and is funded by the VA.
About Joslin Diabetes Center
Joslin Diabetes Center is the world's largest diabetes clinic,
diabetes research center and provider of diabetes education. Joslin
is
dedicated to ensuring people with diabetes live long, healthy lives
and offers real hope and progress toward diabetes prevention and a
cure for the disease. Founded in 1898 by Elliott P. Joslin, M.D.,
Joslin is an independent nonprofit institution affiliated with
Harvard
Medical School.
Joslin Diabetes Center
One Joslin Pl.
Boston, MA 02215
United States
http://www.joslin.org
-------------------------
Med Hypotheses 1998 Mar;50(3):239-51
A chelate theory for the mechanism of action of aspirin-like drugs.
Wang X
Department of Pathology, Cornell University Medical College, New
York,
NY 10021, USA. ***@mail.med.cornell.edu
Two hundred years after the discovery of the pharmaceutical
usefulness
of aspirin, it and aspirin-like drugs, a family with an
ever-increasing number of members, are an indispensable part of
modern
life. However, the question as to how these drugs work in the body
has remained unsettled. It is postulated here that this group of
drugs may exert their therapeutic (and adverse) effects by chelating
various physiologically important metallic cations in the body.
The chelate theory is supported by the vast majority, if not all, of
the observations on these drugs made in the past.
PMID: 9578329, UI: 98237440
Who loves ya.
Tom
Jesus Was A Vegetarian!
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http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
Post by ironjusticeThe use of an antimalarial medication may prevent the onset of
diabetes in patients with rheumatoid arthritis, new Geisinger research
shows.
Researchers examined the records of 2,093 Geisinger patients who
received treatment for rheumatoid arthritis from 2000 to 2008. The
study looked at, among other things, use of the medication
hydroxychloroquine (HCQ) and the development of new cases of diabetes
in these patients.
HCQ was developed to treat malaria but it has also been used to treat
rheumatoid arthritis and other autoimmune diseases.
In patients with rheumatoid arthritis, use of HCQ was associated with
a 53 percent reduction in the development of new cases of diabetes,
the study found.
"Given the relative safety and low cost of this generic drug, HCQ may
be useful in preventing diabetes in other high risk groups," said lead
study investigator and Geisinger rheumatologist Androniki Bili, MD,
MPH.
Researchers don't know how exactly HCQ prevents diabetes onset but
it's suspected that HCQ improves glucose tolerance.
About 23.6 million Americans have diabetes, while 1.3 million have
rheumatoid arthritis.
People with rheumatoid arthritis are at increased risk for diabetes
due to more sedentary lifestyle, chronic inflammation and use of
steroid medications that can cause weight gain.
"We should revisit HCQ in the treatment of rheumatoid arthritis
because, in addition to its disease-modifying properties, it might
prevent the development of diabetes in this high risk group," Dr. Bili
said.
Source: Geisinger Health System
------------------
The iron-binding and hydroxyl radical scavenging action of anti-
inflammatory drugs.
Xenobiotica. 1988 Apr;18(4):459-70.
Aruoma OI, Halliwell B.
Department of Biochemistry, University of London King's College,
Strand Campus, UK.
1. Hydroxyl radicals (.OH) are thought to be generated at sites of
inflammation and to contribute to tissue damage. All anti-inflammatory
drugs tested were able to scavenge .OH generated in free solution at
almost diffusion- controlled rates (rate constants about
10(10)M-1s-1).
2. Much .OH generation in vivo occurs at specific sites, where bound
metal ions (such as Fe2+) react with H2O2 to produce .OH that
immediately attacks the site. Only .OH scavengers that have sufficient
metal-binding ability to withdraw metal ions from this site can
protect against site-specific damage.
3. All anti-inflammatory drugs tested were able to protect against
site-specific damage by .OH in a simple model system in vitro.
Penicillamine, diclofenac sodium, piroxicam, azathioprine, primaquine,
chloroquine and hydroxychloroquine were especially effective.
4. The ability of an anti-inflammatory drug to protect against .OH
formation in vivo depends not only on its rate constant for reaction
with .OH, but also on its metal-binding ability and on the geometry
and redox potential of any metal complex formed.
PMID: 3135672
--------------------------------------------------------------------------
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