accutane can deplete folate and b12. this can cause depression.
probiotics might not work without siga. some sais they can be bad for someone who has sibo, i would think this also has to do with siga.
Vitamin A also functions in a very different role as retinoic acid (an irreversibly oxidized form of retinol), which is an important hormone
-like growth factor
and other cells.
Retinal is the form involved in vision, whereas retinoic acid is involved in growth and cellular functions
......Retinol and retinyl esters (palmitate shown) are the dietary forms of preformed vitamin A. Retinal is essential in vision, and retinoic acid is involved in growth and cellular differentiation. ...
Another form of Vitamin A, retinoic acid, is a key hormone-like growth factor for epithelial cells and other cell types in the bodyhttp://en.wikipedia....sis_A#Mechanism
Retinoic acid suppresses osteoblast activity and stimulates osteoclast formation in vitro, resulting in increased bone resorption and decreased bone formation. It is likely to exert this effect by binding to specific nuclear receptors (members of the retinoic acid receptor or retinoid X receptor nuclear transcription family) which are found in every cell (including osteoblasts and osteoclasts).
This change in bone turnover is likely to be the reason for numerous effects seen in hypervitaminosis A, such as hypercalcemia and numerous bone changes such as bone loss that potentially leads to osteoporosis, spontaneous bone fractures, altered skeletal development in children, skeletal pain, radiographic changes, and bone lesions.
Osteoblast are cells with single nuclei that synthesize bone.
Osteoblasts are specialized, terminally differentiated products of mesenchymal stem cells.They synthesize very dense, crosslinked collagen, and several additional specialized proteins in much smaller quantities, including osteocalcin and osteopontin, which comprise the organic matrix of bone.
brilliant. accutane and telomeres
Retinoic acid signalling is known to be important for a wide variety of physiological processes, including immunomodulatory functions, though its role in immune responses to parasitic infections is not yet fully understood. The precursor of this metabolite, vitamin A or retinol, is an essential nutrient obtained from the diet, and deficiency in this vitamin can lead to an increased susceptibility to infectious diseases (1).
'' RIG-I (retinoic acid-inducible gene 1) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded (in humans) by the DDX58 gene. RIG-I is part of the RIG-I-like receptor family, which also includes MDA5 and LGP2, and functions as a pattern recognition receptor that is a sensor for viruses........RIG-I and MDA5 are involved in activating MAVS and triggering an antiviral response ''
''The results indicated that ATRA reduced the percentage of EV71-infected cells and protected cells against EV71-induced apoptosis. Correspondingly, ATRA increased the production of IFN-α one of the most important antiviral cytokines, at both mRNA and protein levels in EV71-infected cells. In addition, the expression of RIG-I mRNA and its downstream genes was up-regulated by ATRA in EV71-infected cells. Ro 41-5253 abrogated the inhibitory effects of ATRA on EV71. The present findings suggest that ATRA is an interferon-inducing agent with antiviral activity against EV71 in vitro and that its actions are mediated at least in part by RAR-α activity and the RIG-I signalling pathway''
this immune response can happen with larges amounts of retinoic acid even witout a presence of infaction? as wiki state- RIG-I (retinoic acid-inducible gene 1) functions as a pattern recognition receptor that is a sensor for viruses........RIG-I and MDA5 are involved in activating MAVS and triggering an antiviral response '' maybe this mechanisem is out control cause the drug bombed the body with 13-cis retinoic acid? so there is no infection but the body act as if there is?
lets think how an immune system response to infection due to accutane can cause the side affects.
some thaghs i have: isn't the first place to defend against infection is the skin? where the infection will first reach you?also the intestine.the outest layers of the body. would that cause the immune cells to attack the ''infected cells'' so they won't infect the rest of the body- it will make the immune cells to atack the infection with ROS. the drug administraed again and again and with high dose comparing to regular diet vitmain A, so this infection alert state remains and cells kepp dying and replaced by others(or it cycle somehow speeded), becuase every cell being treat as if it is infected, this is the cell prolifiration mechanisem that accutane induces? after all the cell divisions the telomerese get too short and chromosomes/histone/whatever reach it replication limit-hayflick limit, and since
http://en.wikipedia....8px;">29</span>With critically shortened telomeres, further cell proliferation can be achieved by inactivation of p53 and pRb pathways. Cells entering proliferation after inactivation of p53 and pRb pathways undergo crisis. Crisis is characterized by gross chromosomal rearrangements and genome instability, and almost all cells die.
maybe then the body finally reach to the point where it fighthing the accutane, which mean it fighting against itself for stoping itself atacking itself due to a false belive it cells are infected:
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells
what that confusing is that if it is the case then it semms that the retinoic acid itelf induce this defend acording to what i read. maybe more correctly is that that the body induces this defenf as a consequence of retinoic acid toxicity? if not then that's not understood- retinoic acid make the immune system to act against infection and on the same time shuts the immune system down?
Retinoic acid has multiple effects on innate and adaptive immunity, including promoting the differentiation of T and B cells (9,10), modulating cytokine production (11), driving Th2 responses (12,13) and inducing immune tolerance through induction of Foxp3+ regulatory T cells (Tregs) (14),
In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation.
'The regulatory T cells (Tregs), formerly known as suppressor T cells, are a subpopulation of T cells which modulate the immune system, maintain tolerance to self-antigens, and abrogate autoimmune disease. These cells generally suppress or downregulate induction and proliferation of effector T cells. Additional regulatory T cells known as Treg17 cells have recently been identified
those Foxp3+ regulatory T cells (Tregs) , guess who is a good friend of them? FOXO
''In this issue of Immunity, Kerdiles et al. (2010) report that Foxo transcription factors are essential for the development and function of Foxp3-expressing regulatory T (Treg) cells via controlling the expression of genes associated with Treg cell function.''
SO all this make me wonder if that drug caused the body to act agains infection over and over on cells and repalacing them with non infected cells which again persumed as infected till the the telomeres shortened so much that cells reached it replication limit, or befor it?
then foxo took its role so no more infection like fighting will happen cause it will be deadly, or that the cells can't diviede and cell cycle stack so thats also or alone whay foxo is up.
dont know how much of all that is close to the truth and scientific the way i said it,
maybe all the cell death/cell cycle arrest happen cause the body fight pressived infection? by down regulate htert?
hTERT gene produce telomerase which reapir telomeres. accutane can shut htert down. is it for fighting assumed infection?http://www.pnas.org/...2/6662.full.pdfA second pathway of hTERT regulation,identified in the RAR-responsive, maturation-resistant NB4-R1 cell line, results in a down-regulation of telomerase that develops slowly during two weeks of all-trans retinoic acid (ATRA) treatment. This pathway leads to telomere shortening, growth arrest,and cell death, all events that are overcome by ectopic expressionof hTERThttps://www.mskcc.or...>vitamin</span>''ATRA halts telomerase activity and exerts antitumor effects via a rapid decrease of H3-K9 acetylation at the hTERT promoter (39). The protective effect of supplemental retinol against melanoma may be mediated by sunlight exposure (25). http://www.nature.co...l/1207093a.html Retinoic acid receptor and retinoid-X receptor-specific agonists synergistically target telomerase expression and induce tumor cell death http://www.ncbi.nlm....icles/PMC34517/
We identified two levels of regulation of telomerase by retinoids and showed that retinoids can regulate telomerase and telomere length independently of cell maturation, leading ultimately to extinction of the tumor cell clone
…Therefore, the inhibition of telomerase activity correlated with the induction of growth arrest and/or the attainment of a maturated state.''
these is confusing. http://www.nature.co.../1206063f4.html''Note the appearance and subsequent increase of SOD-2 message after 60 h of infection, whereas there is no significant change in expression of alpha-actin. © The relative increase of hTERT binding to telomeres and SOD-2 expression. The estimation of hTERT binding to telomeres is relative to the p21 binding to genomic DNA and the estimation of SOD-2 gene expression is relative to alpha-actin expression. Note an increase in telomeric DNA levels coimmunoprecipitated with the increase in postinfection time, suggesting that TERT protein binds to telomeres. The intensities were quantitated by the procedure described in the Methods section. Note that the increase in the interaction of hTERT with telomeres precedes the increase in SOD-2 gene expression
Edited by Modeaa, Yesterday, 04:38 AM.