2010-12-31

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
Phone: 314-771-5765, Fax: 314-771-5757
E-mail: OC_DOM_HC@sial.com
Ordering & Customer Service
Phone: 800-325-3010

# Opening a Sigma-Aldrich Account
Accounts are generally established for a company or institution
rather than for individuals.
# Your business or institution must have an established
Customer Account with Sigma-Aldrich
to establish an account, and be approved for on-line ordering;
you will need to contact Support by phone.
You cannot establish an account on-line.
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 .]

ironwood tree planting in tucson

12.1: proj.apt`yard/tree#n.ironwood replanting:
. being soaked made it heavy
and more likely to traumatize the roots;
but, I was hoping things would stay in place
if dirt was around before the sleeve was removed .
. the instructions are very different from last year,
saying to pull the sleeve without dirt surrounding it,
and then use your finger to pull some roots loose!
I stayed with last year's advice .
. I cut across the bottom,
and then around the bottom,
then checked that the sleeve would pull up
before packing dirt around it;
but I packed it too tight,
and the whole plant would lift
as I was trying to pull the sleeve out;
so I wondered if I ripped away a layer of roots
as they fell with the soil .
. the instructions reminded me not to add
any supplements like peat moss,
and I notice this was very dark soil
like what was brought in for the privets;
I also added several cups of vitamixed garbage
a few weeks ago,
but that was a small percentage of
what the roots will be exposed to ...
. in short,
I wasn't sure how desert-like the soil was,
so, I arranged the tree to be higher than ground,
with a deep moat around it,
so it's easy to both soak and drain .
. it got a shower to help pack the dirt
around the new root ball,
along with filling the moat .
. it smelled like the root ball's bottom
was overly watered a lot,
but the tree looks good .

preventing frame damage in tadpole trikes

12.13: gear/trike`frame/potholes need suspension:
. the trice front-suspension add-on is expensive,
but it's quite likely the frame will be ruined
unless speeds are low or potholes are avoided .

gear/trike`frame/potholes need rider pivot:
12.13:
. the trice already has rear suspension
which helps deflect rider weight from bending frame;
but that doesn't help z-axis rolling
where one front wheel is potholed but the other isn't
and the whole frame falls into a rolling motion
to one side or another .
. if the rider's chair is frozen to the frame
then the rider's weight is resisting that z-roll,
which could increase stress at the cruciform joint .
12.14:
. how rigidly can riders' weight
prevent rolling about z-axis for potholes?
# if rider's seat were not bolted to main tube,
but instead pivoted sideways,
then there'd be less stress on frame during potholes;
# if seat was closer to main tube,
with thick cusion under rider;
then z-axis rotation could happen stress-free
even without pivot .

12.15: gear/trike/replacing front suspension:
. the cheap sure-tech way to stop
frame bends from potholes
is to unbolt the seat from the z-tube,
make a platform that is anchored to
both the z- & x-tube;
and, bolt the seat to that platform .
. if steering doesn't fit with platform,
it can be moved from sides to center .

2010-12-29

existence proof

12.29: relig/god/existence proof:
. you can't disprove this universe isn't a
conspiracy involving a centralized emotion maker
(emotions aren't personal, they happen against our will
and are a sort of natural disaster:
they alone support overpopulation,
religous wars, and mental illness);
likewise,
you'd hardly deny the existence of terrorists
just because there's no current proof of existence;
therefore,
it would be taking more risk than necessary
to assume there's no conspiracy
unless it causes a dangerous aversion to risk
(if mob's, plagues, or politics
could upset your plans,
then you might want to put god out of mind).
. the corollary of conspiracy theory
is that Shush Happens Inside There!
and, in the long term, a belief in conspiracy
can be a healthy driver of preparation for
several worst-case scenerios converging .

2010-12-24

moving qubes`way on the mac

11.07: vm (virtual machine)-based security:
. an intro to security with virtualization
and a getting started manual for mac os x .
 .  this shows how some security experts have agreed,
vmware`Fusion can make the mac more secure .
[2013 update: my mac was destroyed while using
either vmware`Fusion/linux/pdf reader, or a usb stick.]

2010-12-22

the higher power

12.20: relig/god/the higher power:

. recalling my blog of speeder cameras;
. along with my usual view that
human policing can apply the law unequally;
there's also a god-related issue
(significant since such issues are
splitting the country in half
so you'd expect little reminders of such):

. the god fearing young driver would be saved by
thinking a god is catching every cheating moment;
while the godless would be saved only by
the sure justice of knowing there are robocops
everywhere all the time;
therefore,
robocops could be a symbol of the godless,
and a hate of robocops could be a swipe at
free-thinking anti-dogmatic humanists,
or Democrats .

. can you actually teach kids to fear god?
in the political debate
it's always presented as an option!
(school prayer leads to kids praying;
and packing kids in school leads to
gang violence ... or lots of prayer!)

. I myself thought kids could be saved
either by
stressing the bible as proof of the supernatural
or by diligently watching kids until
their youthful minds became future aware;
but to nix both the supernatural training
and the constant guidance
is tantamount to saying
a kid should remain seeable because nobody sees
-- that is a likely future killer .

. then again,
if you think kids are better off god-aware
imagine how many adults are not god-aware
and yet still caught cheating?
I suppose they figure god is only the devil;
"( so what if God sees all? he loves everything! ).

. the real significance of god
is knowing who has your ears:
is it your selfish impulses?
or a higher power?
but when you call "(god) your higher power
(rather than, say, the Chinese Premiere)
what is your higher power saying?
my clerics say, my books say,
my big fat trust me really told you;
so, it's just my line in the sand,
having fun -- like I always do!

. the Buddha had it right:
the real plain truth is understood by
self agreeing with elders:
without elder checks there is foolishness,
without self checks there is corruption .

2010-12-17

I love the bus? not invented yet

12.17: pol/I love the bus? not invented yet:
. love the bus? after years of
multi-transfer commuting by bus,
I'd once decided that each employer
should be providing their own housing
just so we could avoid the frig'ing bus!
. I was later reminded by industrial accidents,
that there are good reasons
for not living near work!
. reviewing the issue, I finally found
a bus I could love:
. each employer does provide housing for each shift,
and also provides a private bus that links
an employer's home site with their work site;
with such direct routes,
the bus involves no waiting in unsecured places .
. busing works for shopping too,
when part of the gated community model:
your secure id card is the way to get on,
they charge you by debit;
so, there's no more being sardined with
unidentified terrorists or nutty criminals .
. there are direct bus lines between every mall,
and every gated community .
. people with behaviors lose their license to bus,
and must either use pedal cars,
or let relatives do the shopping .
. with the efficiency and safety of
the gated community model,
the usa's citizens could be on the path to
being competitive with chinese communism
while still retaining their std of living;
assuming that std doesn't continue to involve
gross denial of unhealthy lifestyles .
. buses that run clean green fuels,
could significantly reduce usa's exposure to
carcinogens in oil-based fuels;
but the greatest carcinogen in the usa by far
is their ignorance of hormone issues:
diets that raise insulin and cortisol,
and the use of female hormones to control birth .

2010-12-15

peace prize to the voice with no body

12.12: pol/peace prize to the voice with no body:
. the peace prize went to the right person:
the voice with no body!
that voice this year has crystallized the message
that the world's christian's should unite
on an apology to the world's jews,
and reserve an israel-sized chunk of the new world
for a peaceful place where
jews alone are welcome to govern jews, forever .

12.10: co.apt/pol/chinese do deserve nobel peace prize:
. the nobel peace prize winner,
chinese dissident Liu Xiaobo, is a good american;
but in china where the system is not multi-party
he can only foment needless civil war;
and, one good reason for dictatorship
is long avoiding the centuries of civil war
that china has been subject to .
. the chinese leadership shows
true love for its people;
they are like the 2nd coming of christ
doing more for the war on poverty
than any other power on earth .
. they could have just exploited the energy
of an expanding population
to stay in power effortlessly,
but they so loved their people
that they risked their own position of power
by using it to force population controls
against a culture that is notoriously poor:
humans can have 14 girls in a row,
and the chinese traditionally keep having children
until they get at least one boy .
. this measure won't make leadership wealthier,
but in time it will bring wealth to all their subjects .
--
Liu Xiaobo launched Charter ’08,
the manifesto for democracy in China
which landed him an 11-year prison term .
the Norwegian Nobel Committee gave him the prize