leads that are bugging me

[Veneficus]

Well, maybe somebody here can offer something.

I have some notes in regards to the induction and treatment of shock states.

I have tried to follow them out for months now, but have not had any luck.

Here is where I am at.

NfkB,

it is:
proinflammatory
pro thrombotic

but:
antiapoptic

one of the many things that activate it is erythropoietin. Which down regulates IL2 and TNF.

NfkB acting in the nucleus clearly has a greater proinflammatory effect than the erythro. Not suprising since one acts like a steroid and the other like a membrane receptor.

estrogen also has antiapoptotic effects (I cannot figure out if it is from a different receptor than NfkB and can find no research on it.)

Is estrogen synergistic with erythropoietin?

Back to NfkB,

it regulates BCL, which in turn inhibits caspases 3,7,8,9 it also regulates apoptosis by cytochrome C (but I cannot figure out and find no research if it is because it helps cell membrane intergrity of the mitochondria or downregulates cyto C production)

a precursor, AKT, also inhibits bad and bax.

So I am thinking that all of this probably helps to inhibit the onset of apoptosis secondary to cell injury.

But, it doesn't seem to stop the inflammatory response from taking out cells with injured membranes.

It is known that systemic inflammation is a common pathway of shock. There are studies showing antiimmugenic strategies have no effect on outcome.

Does anyone have or know of any studies showing an effect of down regulation of NfkB because I don't have access to any if there are?

Does anyone know anybody who is actively working on this topic I could contact?

 

[RocketMedic]

Take the red pill?


I have no idea what you're talking about, but could it be a delay if the inflammatory process instead of an inhibition?

 

[izibo]

So, I happen to have a smidgen of experience in the NF-κB field and my best piece of advice is to not worry about it. The NF-κB system is profoundly complicated, and in fact, different cell types can activate different NF-κB target genes. To make matters even more complicated, activation of the traditional NF-κB dimer (p50/RelA) by different stimuli (DNA damage vs IL-1 vs TNF) can also change the target gene profile, likely due to costimulatory factors.

If you want to go deeper, there are lots of great resources but you venture down a dark and deep rabbit hole. A good place to start is a review article by Neil Perkins available here. There is also a bit of a dated review on the role of NF-κB in apoptosis in oncogene.

Sorry to not be more helping, but you are asking a profoundly complicated question with no real easy answer. People have written entire textbook chapters on the crosstalk between NF-κB and other signaling pathways and it's role in cell survival.

 

[Veneficus]

So, I happen to have a smidgen of experience in the NF-κB field and my best piece of advice is to not worry about it. The NF-κB system is profoundly complicated, and in fact, different cell types can activate different NF-κB target genes. To make matters even more complicated, activation of the traditional NF-κB dimer (p50/RelA) by different stimuli (DNA damage vs IL-1 vs TNF) can also change the target gene profile, likely due to costimulatory factors.

If you want to go deeper, there are lots of great resources but you venture down a dark and deep rabbit hole. A good place to start is a review article by Neil Perkins available here. There is also a bit of a dated review on the role of NF-κB in apoptosis in oncogene.

Sorry to not be more helping, but you are asking a profoundly complicated question with no real easy answer. People have written entire textbook chapters on the crosstalk between NF-κB and other signaling pathways and it's role in cell survival.

Cool thanks.

Which textbooks I will check that out too.

 

[izibo]

Cool thanks.

Which textbooks I will check that out too.

http://www.amazon.com/dp/0849327946/ref=rdr_ext_tmb

Although you would truthfully be better off reading more recent reviews. It's getting quite dated.

 

[Brandon O]

estrogen also has antiapoptotic effects (I cannot figure out if it is from a different receptor than NfkB and can find no research on it.)

I believe there's a good bit of research looking at this currently.

 

[Doczilla]

Off the top of my head, I don't beleive that E and EPO serve synergystically in shock states or inflammatory states. EPO is activated [among other things] by anemia, and of course shock states--- to stimulate reticulocyte production from the bone marrow. I'm not aware of estrogen as part of any inflammatory cascade or any matrix of shock responses. I could [am probably am] be wrong though.

Of course, EPO is near useless in the short term, because it takes at LEAST 30 days to truly make a difference in H&H.

 

[bigbaldguy]

Ok I vote vent has to put "don't read if dumb" after these kinds of posts so that people like me don't accidently read them and get a headache. Who's with me?

 

[shfd739]

Ok I vote vent has to put "don't read if dumb" after these kinds of posts so that people like me don't accidently read them and get a headache. Who's with me?

Agreed