coronary microvascular dysfunction

 24.2.9: web.health/heart/
coronary microvascular dysfunction:

summary:

. if you feel like a heart attack is happening

but they can't find an obstructed or clogged artery,

that is known as MINOCA:

myocardial infarction [heart cell death due to blood loss]

with non-obstructive coronary arteries 

which can be caused by artery spasms, ripped artery,

or a new condition that is known by many names:

coronary microvascular dysfunction

Coronary microvascular disease

Microvascular endothelial dysfunction

Cardiac syndrome X

Nonobstructive coronary heart disease.

ami.org 2024.2.5

https://www.facebook.com/amidotorg/posts/pfbid022tx3M4kK9x4LdyGzERCRcB7qb3hMtpo1ThRziRvhFdNo6He8v8Ktd7RqMWdL2nPml

The Association of Medical Illustrators is

excited to announce the launch of 

the first round of illustrations through the 

AMI Diversity Fellowship, 

made possible by a grant through Johnson & Johnson’s (J&J) 

Our Race to Health Equity (ORTHE) initiative. 

In recognition, we will be highlighting the work of

each of our Diversity Fellows.

eg, the first illustration highlights

myocardial infarction with non-obstructive coronary arteries.

[!] image: myocardial infarction with non-obstructive coronary arteries 

(MINOCA), can be caused by artery spasms 

or coronary microvascular dysfunction.

interesting that mentions  

"coronary microvascular dysfunction";

it is a new diagnosis with many names...

Small vessel disease

https://www.mayoclinic.org/diseases-conditions/small-vessel-disease/symptoms-causes/syc-20352117

Small vessel disease may also be called:

Coronary microvascular disease

Microvascular endothelial dysfunction

Small vessel disease is treatable but may be difficult to detect. 

The condition is typically diagnosed after finding

little or no narrowing in the main arteries of the heart

despite the presence of symptoms that suggest heart disease.

Coronary Microvascular Disease (MVD)

https://www.heart.org/en/health-topics/heart-attack/angina-chest-pain/coronary-microvascular-disease-mvd

In coronary MVD, the heart's coronary artery blood vessels

don't have plaque, but damage to the inner walls of the blood vessels

can lead to spasms 

or abnormalities in smaller arteries.

Other names for coronary microvascular disease:

Cardiac syndrome X

Nonobstructive coronary heart disease

Treatment

Medications to relax blood vessels including 

beta blockers, calcium channel blockers and nitroglycerin.

Noel Bairey Merz, MD

https://www.cedars-sinai.org/newsroom/what-is-minoca-a-type-of-heart-attack-mostly-affecting-women/

What is MINOCA? A Type of Heart Attack Mostly Affecting Women

. myocardial infarction with non-obstructive coronary arteries 

(MINOCA), is garnering increased attention.

Janet Wei, MD, and Noel Bairey Merz, MD:

MINOCA is a heart attack caused by 

poor blood flow to the heart, 

despite no evidence of major blockage in the arteries,

eg, coronary artery spasms, and

spontaneous coronary artery dissection.

A troubling aspect of MINOCA is that

often when we diagnose a heart attack, 

we rely on a single imaging method

—invasive coronary angiogram—

to tell us if there’s a big blockage in the coronary arteries. 

With MINOCA, the angiogram can look normal.

MINOCA patients are more likely to be female and younger, 

and they’re also more likely to be Black or Hispanic/Latino. 

Social Anxiety Relief by Emma Lou Parker 2022

2022.10.23: bk.psy/schiz/
Emma Lou Parker 2022`A Teen’s Essential Guide to Social Anxiety Relief:

. this is a review of the book:

Emma Lou Parker 2022`

A Teen’s Essential Guide to Social Anxiety Relief: 

Step-By-Step Methods to Help You Overcome Social Anxiety, 

Avoid Triggers, and Find Relief| 

Feel Confident, Comfortable, and Happy in Any Situation!

https://amzn.to/3DqLnzV[ad]

4-star/a method with some proven success:

fish oil reduces risk except for angina patients

22.1.2:  2.8: news.health/diet/omega-3/heart
/fish oil reduces risk except for angina patients:

Mayo Clin Proc. 2021 Feb

https://pubmed.ncbi.nlm.nih.gov/32951855/

Effect of Omega-3 Dosage on Cardiovascular Outcomes: 

An Updated Meta-Analysis and Meta-Regression of Interventional Trials.

Aldo A Bernasconi, et al.

commentary:

www.sciencedaily.com/releases/2020/09/200917084102.htm 

"People should consider the benefits of omega-3 supplements,

at doses of 1000 to 2000 mg per day

-- far higher than what is typical, 

even among people who regularly eat fish."

Berberine prevents heart failure through endothelial and calcium function

 2021.8.9: 9.4: health/diet/heart/Berberine/
prevents heart failure through endothelial and calcium function:

GreenMedInfo Research Group July 30th 2021

https://www.greenmedinfo.com/blog/seven-herbs-and-supplements-heart-failure

. something extracted from berberine

is blocking calcium influx, thereby reducing

the risk of heart failure.

Acta Pharmacol Sin. 2010

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002834/

Min-you Qi, Yu Feng, De-zai Dai, Na Li, Yu-si Cheng, Yin Dai. 

CPU86017, a berberine derivative, attenuates cardiac failure

through normalizing calcium leakage 

and downregulated phospholamban 

and exerting antioxidant activity. 

Front Physiol. 2020

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546405/

Miyesaier Abudureyimu, Wenjun Yu, et al.

Berberine Promotes Cardiac Function by 

Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure. 

. enhancing endothelial function helps heart:

Cardiovasc Drug Rev. 2001 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999047/

C W Lau, X Q Yao, Z Y Chen, W H Ko, Y Huang. 

Cardiovascular actions of berberine. 

. "Endothelial dysfunction is an important early event in the

pathogenesis of atherosclerosis. 

The mechanisms underlying endothelial injury are numerous

and linked to metabolic alteration. 

In obesity and insulin resistance, 

the increased secretion of proinflammatory cytokines 

and decreased secretion of adiponectine, 

the increased circulating levels of free fatty acids, 

and hyperglycaemia may alter gene expression and cell signalling in the vascular endothelium, 

contributing to changes in the release of endothelium derived factors. 

Dysfunctional endothelium is characterized by activation of NADPH oxidase, 

uncoupling of endothelial nitric oxide synthase (eNOS), 

increased expression of endothelin-1, 

an imbalance between the production of vasodilators and vasoconstrictor mediators, 

and induction of adhesion molecules

[31]. 

The altered endothelial homeostasis, in turn, 

contributes to plaque initiation and progression. 

It is associated with most cardiovascular disease, such as 

hypertension, coronary artery disease, chronic heart failure, 

peripheral artery disease, diabetes and chronic renal failure

[32]. 

Endothelial cells exposed to hypercholesterolemia show a 

reduced capacity to release endothelium-derived relaxing factors, 

because of LDLc promotion of endothelial eNOS downregulation

[33]. 

Lowering cholesterol levels appears to improve endothelial function

[34]. 

In diabetes and insulin resistance, other mechanisms may trigger endothelial dysfunction. 

Insulin signalling is altered in these two conditions, 

and affects the pathway leading to phosphorylation and activation of eNOS, 

which is also, in this case, dramatically downregulated

[35]. 

eNOS represents a major weapon of endothelial cells to fight vascular disease. 

It generates nitric oxide (NO), whose role is to dilate blood vessels

and maintain vascular homeostasis by stimulating cGMP

[36]. 

Several studies have suggested a central role of endothelial AMPK

in maintaining physiological functions, such as

mediation of eNOS activation in response to shear stress

[37], 

modulation of endothelial cell energy supply

[38], 

protection from apoptosis

[39] 

and regulation of inflammation, angiogenesis, and maintenance of perfusion

[40,41]. 

Impairment of endothelium dependent relaxation (EDR) 

represents reduced eNOS derived NO bioavailability, 

and is the first step in endothelial injury. 

It is present also in the absence of vessel damage. 

In 2000, Ko et al[42], by in vitro investigation, 

demonstrated that BBR has not only vasorelaxant 

but also antiproliferative effects. 

According to their results, BBR could act both on the endothelium 

and on the underlying vascular smooth muscle cells to induce relaxation 

(Figure (Figure1).1). 

NO, is likely involved in the EDR. 

More recently, this mechanism has been clarified in endothelial cells isolated from rat. 

It was confirmed that the vasodilatant effect of BBR

was mediated by eNOS leading to NO production 

through activation of the AMPK cascade. 

Moreover, BBR counteracts several adverse effects of hyperglycemia on the endothelium, 

including the inhibition of high glucose-induced reactive species 

intracellular accumulation and cellular apoptosis and inflammation, 

which characterize vascular injury

[31,43]. 

Another recognized effect of BBR is the significant decrease in

the number of adherent monocytes on endothelial cells, 

which is a key event in the early stages of atherosclerosis. 

Furthermore, BBR suppresses the activation of the 

nuclear factor-κB (NF-κB), 

the expression of adhesion molecules (VCAM-1 and ICAM-1) 

induced by hyperglycemia

and the high glucose-induced elevation of several pro-inflammatory cytokines and chemokines, 

including tumor necrosis factor-α, IL1-β, IL8 and MCP1, 

which are other targets of NF-κB 

involved in the development of atherosclerotic plaques

[43]"

fig 1:

. Berberine enhances endothelial function 3 ways:

it affects AMPK (Adenosine mono-phosphate kinase)

that affects eNOS (Endothelial nitric oxide synthase);

it lowers LDL-cholesterol and triglycerides;

and, it improves insulin sensitivity.

enzymedica Berberine 60 /$20.62

https://www.lifeextension.com/vitamins-supplements/item53349/berberine

Enteric-coated to prevent self-aggregation and formation of berberine crystals that reduce absorption.

Enzymedica's Berberine is provided in a

targeted delivery capsule 

to prevent release of berberine in the stomach. 

since in an acidic environment, berberine will bind with other berberine molecules

to form insoluble complexes that do not get absorbed. 

Prevention of the formation of these complexes

may improve the absorption of berberine.

Amount Per Serving

Berberine HCI (97%) (from berberis vulgaris extract) (seed) 500 mg

Leucine 50 mg

Other Ingredients: 100% vegetarian capsule (cellulose, gellan gum, water), 

rice concentrate, calcium laurate

[Calcium laurate helps powders flow into capsules 

and holds those powders together.]

Dr. Michael Murray:

https://www.iherb.com/pr/enzymedica-berberine-60-capsules/81507

"Berberine is commonly harvested from the flesh, roots or bark of plants 

like barberry, goldenseal and Oregon grape. 

Unlike many other formulas, this product is sustainably sourced from 

barberry seeds and does not require the plant to be sacrificed in its production.

sublingual instead of enteric coated?

Nutricology, Berberine 500, 90

https://www.iherb.com/pr/nutricology-berberine-500-90-vegetarian-capsules/82073

Hydroxypropyl methylcellulose, 

Nu-MAG® (rice extract, rice hulls, gum arabic, sunflower oil), 

silicon dioxide, microcrystalline cellulose.

https://ribus.com/nu-mag/

Nu-MAG offers formulators a Certified Organic alternative to Magnesium Stearate, 

so organic tablets requiring a lubricant can now be produced. 

Thorne Research, Berbercap, 60 

https://www.iherb.com/pr/thorne-research-berbercap-60-capsules/18577

Microcrystalline cellulose, leucine, silicon dioxide.

Berberis concentrate berberine HCl 85%.

Berberine HCl (from Indian Barberry extract) (root) (Berberis aristata) 200 mg

Whitaker Nutrition, Clinical Grade, Berberine, 90 Capsule

https://www.iherb.com/pr/whitaker-nutrition-clinical-grade-berberine-1-500-mg-90-capsules/101131

Berberine Hydrochloride (BerberPure™) 500 mg (take 3)

Microcrystalline cellulose, gelatin, magnesium stearate, gum acacia, silica. 

a doctor's path to reversing artery plaque from insulin resistance

19.12.2: tv.med/heart/a doctor's path to 
reversing artery plaque from insulin resistance:
Ford Brewer MD MPH Apr 18, 2017
How I Reversed 20 years of Arterial Plaque: 
Heart Attack Proofing?
. ACE inhibitors, like statins,
are designed for one thing
{lower blood pressure, lower cholesterol}
but they are actually most helpful because
they are reducing inflammation.
. he reduced high-glycemic carbs,
[noted in the captioning]
and because that lowers insulin
which improves blood lipids and pressure,
he was able to lower his dose of medications;
. he also used niacin, and ate salmon every day.

arrythmia better or worse from low iron?

19.11.25: med/heart/afib/
arrythmia better or worse from low iron?
. an elder who visited the doctor for afib
(atrial fibrillation or arrythmia)
was told that one aggravating factor was that
her ovo-vegetarianism had resulted in low iron
and that she needed to take iron supplements.
. I was surprised to hear this,
because it was previously believed that
higher iron levels involved oxidative stress
and men were being encouraged to give blood
in order to keep their iron low.
[Amer J Epi 1998]
. however, ...

how moderate red wine use affects hormones

19.11.11: web.health/hormonics/diet
/red wine and alcohol:
. red grapes fermented or not
may raise levels of free testosterone (T)
by reducing conversion of T into estrogen;
and can also lower the binding of T with SHBG.
. alcohol may reduce inflammation for heart,
[Dr.Sears, the inflammation zone]
and it may reduce what is binding T,
but may also convert more T to estrogen,
and might reduce progesterone levels.
. red wine compared to white wine,
gives more free T and lower SHBG levels.

how #vegan diets are more prone to bleeding

9.6: health/diet/how vegans are more prone to bleeding:
9.10: summary:
. vegans seem more prone to bleeding;
Sears's zone diet research suggests
that there is greater risk of bleeding
when taking high-dose fish oil,
because the omega-3 oil EPA
greatly exceeds the balancing effects of
arachidonic acid (AA) omega-6 oil.
. it is quite likely that the converse is true,
those with very low levels of AA,
are going to have a bloody EPA/AA ratio
even if their EPA is not high.
. one of the richest sources of AA is egg yolk,
and AA may be why a 2018 study showed
Chinese eating one yolk daily can
reduce their risk of bleeding death.
. a great vegan source for both protein
and the omega-6 that may be converted to AA,
is chickpeas (1.1g omega-6 per 100g);
of course, nuts and seeds
are the richest source of omega-6
other than processed oils.
. chia seeds and walnuts are balanced:
chia: 5.8g omega-6, 17.5g omega-3.
walnuts: 38g omega-6, 9g omega-3;
walnuts are rich in polyphenols too.

can you trust Consumer Reports with vitamin D advice?

3.19: mag.health/diet/vit'd/
can you trust Consumer Reports with vitamin D advice?:
Consumer Reports [cr] on Health april 2019:
"do you really need more vitamin D?" [vd]
. new study with 2k IU for 5 years
didn't reduce risk of cancer or heart disease;
1600 IU in elders didn't prevent falls or build bone.
. this article implies that these are good studies
and that all prior studies showing benefits from vd supps
are all bogus or defective;
but this article has done nothing to prove that.
. if all the studies are good
it could mean that vd alone doesn't help;
you need other dietary and lifestyle changes too.

naturopath Frank Cooper early warning about Interesterified fats

2017.11.13: web.med/naturopaths/
Frank Cooper (Naturopathic Nutritionist based in Australia):
I was impressed that when Interesterified fats
were raising alarm bells in 2009,
Frank Cooper warned about them a year earlier;
I wondered what he is doing now,
and he seems to have lost web presence in 2013.

calc channel blockers control #emf symptoms including #afib

10.15: web.med/afib/calc channel blockers 
control emf symptoms including afib:
Mercola 2017.9:
. cell phone and other wireless fields
such as smart electricity meters
that are too mild to have thermal effects
(so they won't cook you like a microwave)
can still harm you via VGCC activation
(a cell's voltage-gated calcium channels)
Common heart problems linked to EMF exposure
include: Cardiac arrhythmias
(associated with sudden cardiac death)
Atrial fibrillation / atrial flutter.
[J Chemical Neuroanatomy 2016]
. put a Faraday cage around your bed,
as EMFs are known to disrupt sleep.

Dr Rhonda Patrick` #leakygut may be a major cause of #heart disease

4.10: news.health/heart/diet/Dr Rhonda Patrick`
leaky gut may be a major cause of heart disease:
Dr.Patrick doesn't use the term "leaky gut"
perhaps because it is controversial;
but among those who do, they are talking about
the same thing Dr.Patrick says here:

omega-3 medicinal effects

10.21: web.health/diet/omega-3/medicinal effects:
12.27: summary:
. fish oil has long-chained omega-3
that is very valuable for reducing disease;
you can make some yourself with
plant-based omega-3, but not much.
. plant-based omega-3 was not helpful for
reducing the risk of circulation disorders
yet one study showed it reduced the risk of
macular degeneration.
. some studies showed that supplements did not help
reduce risk of cerebrovascular disease,
only a diet of whole fish helped.
. one study showed high-dose supplements
did help with macular degeneration,
while another study showed that
low dose supplements did not help.
. fish is a source of mercury, PCB's and dioxins;
fish oil supplements that are 3rd-party tested
may help with heart disease, cancer,
arthritis, macular degeneration
and mental illness.

#grains promote blood clots?

web.health/diet/grains/grains promote blood clots?:
10.12: summary:
. saturated fats are safe if not mixed with grains;
oats are among the safest grains, but aren't paleo:
they may promote leaky gut, inflammation,
and turn palmitic saturated fats against you .

new normal sugar doubles heart disease risk

7: news.health/new normal sugar doubles heart disease risk:

. sugar has been shrugged off as merely fattening;
but, it can also lead to cardiovascular disease
as well as many other chronic diseases,
including diabetes mellitus,
liver cirrhosis[from fructose in sugar],
and dementia [from cholesterol raised by sugar]
— all linked to metabolic perturbations involving
dyslipidemia, hypertension, and insulin resistance .
. in the latest study (JAMA Internal Medicine, Feb 3),
added sugars were defined as
those used in processed or prepared foods,
including sugar-sweetened beverages,
packaged cereals and breads, etc;
but not those that occur naturally
in fruit and vegetables.
. sugar counted for at least 25% of the calories
among 10% of the group;
that group had a 2.75 times greater risk
of cardiovascular disease mortality
compared to an sugar intake of less than 10%.

corn syrup without fructose

7.7: pol/healthcare/corn syrup has no reason
without the unhealthy high fructose:
. even though fructose is
more expensive and unhealthier,
if fructose weren't added,
then corn syrup would not be sweet,
and then you'd have no reason to
add the corn syrup itself
other than it being a cheaper source of calories,
which gets: "( huh, why I am eating
so many empty calories anyway?
it doesn't even taster better! )
-- still, it would be just as filling, [9.27:
and then it would make you hungrier later;
so, I'm sure your food processors
would continue to add corn syrup to everything
even if it didn't have sweetening fructose .]

best diet for heart recovery

4.12: co.health/ask.lef.org/best diet for heart health:
What is the best diet for a 
recovering heart attack patient?
(legume, paleo, zone, heart,)
Transpower (3/5/2012)/Try the Paleolithic Diet:

lean meat (skinless turkey and chicken, low-fat beef),
fish, vegetables, fruits, and nuts.
High protein, low carb, low fat.[/quote]

me:
. concerning the Paleo diet,
beware lumping together legumes with grains;
Paleo experts love to point out how toxic soy is,
but black turtle beans are not nearly as toxic,
and they have equally high quality protein .
. beans are a great way to control the rate of
both glucose and protein;
and, according to Dr.Darmadi-Blackberry,
(Asia Pac J Clin Nutr. 2004;13(2):217-20)
Legumes are the most important dietary predictor
of survival in older people of various ethnicities.
. I get half my protein from red or black beans,
and half from LE whey and few eggs;
mixed with olive oil, and rosemary .
. along with plenty of greens, cruciferous veg,
tomato sauce, boiled yam,
selenium, magnesium, seaweed, and LE fish oil,
I consider that diet consistent with a Zone diet
-- a less-toxic version of the Soy Zone .
. listen to paleo's discuss beans:
. here's the science of bean prep:
. I'm not too fussy about bean prep myself;
I bring the beans to a boil, and then let sit overnight;
toss the water and vitamix-puree
with oil and rosemary herb;
pressure cook for 30min at 210F
(see my cooking gear).
-------------------------------------------------------------------------------------------------
"Futuro Pressure Cooker"   "Auto Sensor Induction Cooktop"

born-again conservative with Congressman Aaron Schock

5.10: news.pol/born-again conservative with
Congressman Aaron Schock:
Men's Health magazine/The Ripped Representative
America's Fittest Congressman:
The Aaron Schock Workout & Summer Challenge

se-methylselenocysteine preventing cancer

Se-methylselenocysteine -- at iherb and amazon--
is a uniquely non-toxic form of selenium,
the essential mineral;
I've routinely taken 20doses a day
-- that's 4mg*... (that would be too toxic in other forms).
. here are more references to articles about
how it prevents cancer, and maybe old-age blindness
(this will be added to my selenium knol).

12.12: web.health/se/se-methylselenocysteine:
TRAIL (TNF-Related Apoptosis-Inducing Ligand)
International Journal of Oncology May 2009 Volume 34 Number 5

. Se-MSC rapidly and specifically down-regulates
expression of the Bcl-2 at transcriptional level.
The forced expression of Bcl-2
attenuated Se-MSC plus TRAIL-mediated apoptosis,
suggesting that Se-MSC's reduction of Bcl-2 expression
is critical to the increased sensitivity
to TRAIL in renal cancer cells.
In addition, we demonstrate that the synergistic effects
of Se-MSC and TRAIL
result from the activation of the
caspase-dependent pathways.
Co-administration of HA14-1,
a small molecule Bcl-2 inhibitor
and TRAIL increased apoptosis in Caki cells.
Taken together, Se-MSC-mediated down-regulation of Bcl-2
is able to sensitize Caki cells for
TRAIL-induced apoptosis.

Programmed Cell Death

Programmed cell death (PCD), or apoptosis,
can be triggered by a wide range of stimuli,
including cell surface receptors like Fas
or tumor necrosis factor receptor 1 (TNFR1).
It constitutes a system for the removal of
unnecessary, aged, or damaged cells
. the relative abundance of
proapoptotic and antiapoptotic proteins
determines the susceptibility of the cell
to programmed death.

The proapoptotic proteins Bax, Bad, Bid, Bik, and Bim
contain an a-helical BH3 death domain
that fits the hydrophobic BH3 binding pocket
on the antiapoptotic proteins Bcl-2 and Bcl-xL,
forming heterodimers that block
the survival-promoting activity of Bcl-2 and Bcl-xL.

. things that result in more pro-apopt's
include: growth factor withdrawal
, genotoxic insult
, uv irradiation,
-- this reminds that chronically high
insulin (a growth factor)
can reduce one of your own sources of pro-apopt's .

The proapoptotic proteins act at
the surface of the mitochondrial membrane
to decrease the mitochondrial transmembrane potential
and promote leakage of cytochrome c.
In the presence of dATP,
cytochrome c complexes with and activates Apaf-1.
Activated Apaf-1 binds to downstream caspases,
such as pro-caspase-9,
and processes them into
proteolytically active forms.
This begins a caspase cascade
resulting in apoptosis.

Smac/Diablo is released from the mitochondria
and blocks IAP proteins that normally interact with
caspase-9 to inhibit its conversion to
the apoptosis-effecting caspases-{3, 6, 7}

The graphic shows the conserved apoptotic pathway
in the organism C. elegans .
CED-3 encodes a caspase whose function is facilitated by CED-4,
which is highly similar to Apaf-1.
CED-4 function is blocked by CED-9,
which protects cells against apoptosis
and is similar to the human antiapoptotic protein Bcl-2.
CED-9 activity is inhibited by EGL-1,
which is similar to the proapoptotic Bcl-2 family members.

Se-methylselenocysteine inhibits
phosphatidylinositol 3-kinase activity
Breast Cancer Res (2005) 7: R699-707

Se-methylselenocysteine (MSC),
a naturally occurring selenium compound,
is a promising chemopreventive agent
against in vivo and in vitro models of
carcinogen-induced mouse and rat mammary tumorigenesis.
We have demonstrated previously that MSC
induces apoptosis after a cell growth arrest in S phase
in a mouse mammary epithelial tumor cell model (TM6 cells) in vitro.
The present study was designed to examine the involvement of
the phosphatidylinositol 3-kinase (PI3-K) pathway
in TM6 tumor model in vitro after treatment with MSC.
RESULTS: PI3-K activity was inhibited by MSC
followed by dephosphorylation of Akt.
The phosphorylation of p38 MAPK was also downregulated
after these cells were treated with MSC.
In parallel experiments MSC inhibited the
Raf-MEK-ERK signaling pathway.
CONCLUSION:
These studies suggest that MSC blocks
multiple signaling pathways
in mouse mammary tumor cells.
MSC inhibits cell growth by inhibiting the activity of PI3-K
and its downstream effector molecules
in mouse mammary tumor cells in vitro.

Se-methylselenocysteine (MSC) chemically synthesized:
. [these 2 ref's were given]:
# SYNTHESIS OF [TRIMETHYLSELENONIUM-SE-75 IODIDE
FROM [SELENOCYSTINE-SE-75]
Source: ANALYTICAL BIOCHEMISTRY Volume: 137 Issue: 1 Pages: 205-209
Published: 1984 Reprint Address: FOSTER, SJ (reprint author),
UNIV WISCONSIN, DEPT NUTR SCI, MADISON, WI 53706 USA
ISSN: 0003-2697
# Chemical Form of Se,
Critical Metabolites, and Cancer Prevention:

Methylated selenides are prominent metabolitesat the dietary levels
used for obtaining anticarcinogenic effects with selenium.
The present study reports the chemopreventive activities
of 2 novel selenium compounds,
Se-methylselenocysteine and
dimethyl selenoxide,
Other treatment groups were supplemented with either
selenite or selenocystine for comparative purposes.
Results of the carcinogenesis experiments showed that
the relative efficacy with the four compounds was
Se-methylselenocysteine > selenite
> selenocystine > dimethyl selenoxide.
In correlating the chemical form
and metabolism of these selenium compounds
with their anticarcinogenic activity,
it is concluded that:
(a) selenium compounds that are able to generate
a steady stream of methylated metabolites,
particularly the monomethylated species,
are likely to have good chemopreventive potential;
(b) anticarcinogenic activity is lower for selenoamino acids,
such as selenocysteine following conversion from selenocystine,
which have an escape mechanism via
random, nonstoichiometric incorporation into proteins;
(c) forms of selenium, as exemplified by
dimethyl selenoxide,
which are metabolized rapidly and quantitatively
to dimethyl selenide and trimethylselenonium
and excreted,
are likely to be poor choices.
We also undertook a separate bioavailability study
using
Se-methylselenocysteine
, dimethyl selenoxide
, and trimethylselenonium
as the starting compounds for delivering selenium with
one, two, or three methyl groups,
and measured the ability of these compounds to restore
glutathione peroxidase activity in selenium-depleted animals.
All three compounds were able to
fully replete this enzyme,
although with a wide range of efficiency
(Se-methylselenocysteine >
dimethyl selenoxide > trimethylselenonium),
suggesting that complete demethylation
to inorganic selenium
is a normal process of selenium metabolism.
However, the degree to which this occurs
under chemoprevention conditions
would argue against the involvement of selenoproteins
in the anticarcinogenic action of these selenium compounds.

-- Sodium selenite was obtained from
Sigma Chemical Co. (St Louis, MO, USA).
--. wholesaler only:
but they do have Se-methylselenocysteine:
M6680 Sigma Se-(Methyl)selenocysteine hydrochloride 95% (TLC)

CAS Number: 863394-07-4
Empirical Formula (Hill Notation): C4H9NO2Se · HCl
Molecular Weight: 218.54
MDL number: MFCD03412450
PubChem Substance ID: 24278564
Description: Se-(Methyl)selenocysteine
. a chemopreventive agent that blocks
cell cycle progression and proliferation of
premalignant mammary lesions;
and, induces apoptosis of cancer cell lines in culture.
M6680-100MG /$ 164.50

Sigma-Aldrich Corp
St. Louis, MO, USA
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12.12: news.health/se/se-methylselenocysteine/Protease inhibitors:
Protease inhibitors suppress apoptotic features induced by MSC

These results confirm previous observations
that caspase-3 is crucial for inducing apoptosis by MSC treatment,
and further suggest the possibility that
an unknown member of the serine protease family
is involved in MSC-mediated apoptosis.
Our results strengthen the possibility that
MSC can be used to prevent or cure cancer
as either a chemopreventive or a chemotherapeutic agent.
Further studies are required to differentiate between
the chemopreventive effects on normal cells
and cancer cells in vitro.

12.26: health/se/age-related macular degeneration:

I lamented how mom's eyes still got cataracts
even with supplemental selenium
-- not because selenium is quack
but because of
stress-induced melatonin disfunction
not allowing the selenium to be useful;
and now hearing about macular degeneration
I found only one article saying it helps that
when I know it helps so much more
(anti-cancer, anti-heart disease)
because of the way it enables selenium!

. in answering the question:
Does melatonin have any bad side effects
in someone mom's age?

here's something that starts as a warning
"(replacement of melatonin just for being elderly
is not recommended)
but actually becomes a great encouragement:
Although elderly people often have difficulty sleeping
it's not from being elderly
but from being either emotionally ill
(making too many stress hormones
that suppress melatonin secretion)
or using drugs that suppress melatonin secretion
(e.g., aspirin, ibuprofen, beta-blockers).
Adults with insomnia, heart disease, or schizophrenia
routinely have lower melatonin levels.

I found this study ok'ing elderly women 64 to 80 years
(it measures cortisol and dhea!)

Effects of six months melatonin treatment
on sleep quality and "serum concentrations of
estradiol, cortisol, dehydroepinadrosteron sulfate,"
and somatomedin C in elderly women
M. Pawlikowski, M. Kolomecka, A. Wojtczak & M. Karasek:
October 9 , 2002 NEUROENDOCRINOLOGY LETTERS

CONCLUSIONS:
On the basis of this preliminary open study
it seems that melatonin administration
may be beneficial for elderly subjects.
A significant decrease of estradiol concentrations
was observed after 6 months of the melatonin treatment
in comparison to initial levels.
IGF-I was found to be slightly but significantly
increased after the 6 months melatonin therapy.
Cortisol levels did not change significantly,
during the melatonin treatment.
DHEAS concentrations increased
after melatonin therapy.
-- a higher DHEAS/cortisol ratio .
Melatonin treatment did not influence significantly
either the parameters of total blood count
or glucose and serum lipids levels.
OBJECTIVES:
The role of melatonin in aging
is still under debate.
Therefore, an open pilot study on the effects of melatonin
was performed in elderly women.
SUBJECTS AND METHODS:
The study was performed on 14 women (volunteers),
aged from 64 to 80 years (mean age 71±4.6 years).
Melatonin (2 mg daily at 19:00 h) was administered during 6 months.
Before and after melatonin treatment
the peripheral venous blood samples
were taken in the morning (approx. at 08:00 h)
after the overnight fast.
The total blood count, glucose, total cholesterol,
LDL, HDL, and triglycerides were estimated by
routine laboratory methods.
The serum concentrations of the following hormones
were determined: 17-beta-estradiol,
dehydroepiandrosterone sulfate (DHEAS),
cortisol, and somatomedin C (IGF-I).

12.26: web.health/se/macular degeneration/se's role:
links from i-care:

# Glutathione and its related enzyme precursor amino acids
(N-Acetyl-Cysteine, L-glycine and glutamine,
as well as selenium)
are protective against damage to
human retinal pigment epithelium cells,
and may help prevent retinal damage in AMD.
Invest Ophthalmol Vis Sci 1993 Dec;34(13):3661-8
# Consumption of fruits and vegetables is protective against
progression of macular degeneration.
Cho, Seddon, et al Arch Ophthalmol. 2004 Jun;122(6):883-92
# In a clinical trial 60% of subjects with ARMD
or diabetic macular edema [...] So Med J, 1987.

[. interesting term: diabetic macular edema
had me convinced that metabolic disorder
-- caused from the use of carb's
by carb'intolerant elders --
was the primary reason elders were getting armd .
so another source of damage besides
not getting the se to the gluthione peroxidase
is not having the circulation for
getting the glutathione to the retina .]