tryingtohelp2014

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  1. must take the active form of riboflavin... R5P riboflavin 5 phosphate. take 10mg 3x a day
  2. Repairing the long-term damage from Accutane

    I don't understand why there is so much negativity? I haven't heard of many people posting about low body temperature on here ever, which is definitely an indicator of a slowed metabolism. So like I'd rather get tested anyways. Vitamin A has been proven to slow down your thyroid function....? if you have a fitbit... this can track your heart rate all day ... i would bet everyone with long term dry skin and joint pain have low tolerance to cold and a low heart rate and body temp. Anecdotal... in the comment section of this article... http://www.forefronthealth.com/vitamin-a-and-hypothyroidism/
  3. Repairing the long-term damage from Accutane

    excellent... need more complete lists like this. lots of thyroid symptoms for sure. tell me you dont match almost all of these symptoms.... http://hypothyroidmom.com/are-you-living-life-with-thyroid-brain-fog/ Thyroxine is important for both collagen synthesis and matrix metabolism2. Hypothyroidism causes accumulation of glycosaminoglycans (GAGs) in the extracellular matrix, which may, in turn, predispose to tendon calcification15. GAGs are involved in the pathogenesis of carpal tunnel syndrome during hypothyroidism15. Elevation of (GAGs), IL6 and TNF has also been reported in exophtalmos in hyperthyroidism16–18. Tendinopathy can be the presenting complaint in hypothyroidism, and symptomatic relief can be obtained by appropriate management of the primary thyroid deficiency19, while calcific tendinopathy has been associated with thyroid dysfunctions20. calcified ligaments and tendons
  4. Repairing the long-term damage from Accutane

    what is resting pulse and temp? Noncancerous conditions that can raise LDH levelsinclude heart failure, hypothyroidism, anemia, pre-eclampsia, meningitis, encephalitis, acute pancreatitis, HIV and lung or liver disease. Tissue breakdown releases LDH, and therefore LDH can be measured as a surrogate for tissue breakdown, e.g. hemolysis. Iodine deficiency produces hypercalcemia and hypercalcitonemia in rats. Clark OH, Rehfeld SJ, Castner B, Stroop J, Loken HF, Deftos LJ. Abstract To determine the effect of thyroid-stimulating hormone (TSH) on secretion of calcitonin by the thyroid, 50 male Sprague-Dawley rats were randomly separated into seven groups. The groups received different diets, medications, or operations [propylthiouracil (PTU), iodine-deficient diet, (LID), acute or chronic thyroxine treatment, sham operation (SO), hemithyroidectomy (Htx), and total thyroidectomy (Ttx)]. two weeks to six months later, serum TSH concentrations were increased in the Htx, Ttx, and LID groups when compared with SO animals. Serum calcitonin concentrations were increased in the LID- and PTU-treated groups and were decreased in animals that chronically received thyroxine. Serum calcium concentrations were increased in the LID animals, decreased in the Ttx animals, and were similar in the other groups. These findings suggest that TSH stimulates both follicular and parafollicular cells in the rat thyroid and that iodine deficiency causes hypercalcemia and hypercalcitonemia.
  5. Try Hi-dose Riboflavin 5 phosphate (vitamin B2) and tell me how it goes.
  6. Repairing the long-term damage from Accutane

    Everyone with long term Dry Skin and joint pain.... please private msg me your resting heart rate and waking morning temperature. mine is 97.1 upon waking and my resting heart rate is between 51-53bpm.
  7. Repairing the long-term damage from Accutane

    like KSman asks people in the TRT thread...go by symptoms. 1. what is your temperature throughout the day? low? 2. what is your resting heart rate? low? 3. did you lose the hair around your ankles and shins after accutane? 4. do you have cold extremities...hands and feet? 5. have you been tested for the MTHFR 677T mutation (two from this thread are homozygous yetanotheraccutane victim and movingonmusicgal) In a pm from movingon.... she had total joint pain relief from 25 mg a day of lugols iodine) its very important to take selenium before trying high doses of lugols. Also very important to work your way up. 1 drop 2 drops 3 drops etc of 2% lugols... until you get to 10 (25mg) active forms of the cofactors would be best in case of a polymorphism i.e. riboflavin 5 phosphate instead of the generic b2. in theory the lugols should help you produce t4...then the cofacors are needed to convert it to t3 and also mop up any ROS along the way. read all of the comments from lugols on amazon . kind of crazy. PFS anecdotes http://www.propeciahelp.com/forum/viewtopic.php?t=6521
  8. Repairing the long-term damage from Accutane

    The very frst post on this huge thread..he states these symptoms: Dry Eyes (Severe) - E.D/ Low Libido (Started last year and has gone on consistently since) - Hair-loss (Including eyebrows, facial hair 'gaps' and body hair) - Slow Healing (Shaving is a pain now - No, it's not my technique) - Lack of sebum (oil) - Brain Fog/ Memory problems - Somewhat minor - Anxiety (mainly because of the other side effects - i.e. dry eyes causing me to feel embarassed about eye contact) - Excessive hair (Not related to head, but my beard grows high up on cheeks and even on the outside of my nose) - I believe I look older than I should due to lack of oil - Joint/Muscle problems - Aches/ Slow recovery - Excessive sweating.. Terrible if I go running at the gym, for example. - Dry mouth - Nosebleeds more than I should - Fatigue These are ALL mimics of iodine deficiency and hypothyroidism. The effects of vitamin A on thyroid hormone production and action have been known for many years. In the 1940s, Simkins demonstrated that patients with hyperthyroidism, were successfully treated with high dose of vitamin A (1) . When treated with vitamin A, these hyperthyroid patients had decreased symptoms of hyperthyroidism as well as decreased metabolic rate. Shadu and Brody studied this effect in euthyroid rats which were fed 30,000 IU of vitamin A per day for 7 days (2). The vitamin A fed rats had a 10% decrease in oxygen consumption and interestingly were found to have a 35% decrease in thyroid weight. The authors hypothesized that vitamin A suppresses pituitary thyrotropic hormone secretion thereby decreasing thyroid hormone production and oxygen consumption. This was the first suggestion that large doses of vitamin A may be affecting thyroid hormone production and function through a central mechanism All of these could be related to Iodine uptake problems. research NIS transporters and retinoids Vitamin A and or retionids could be covering the goiter problems, but affecting every other system. We could have a NIS transporter problem after accutane that stops the iodine from entering the cells. The impact of retinoids on the thyroid axis http://www.eje-online.org/content/170/6/R253.full.pdf http://ajcn.nutrition.org/content/86/4/1040.full Vitamin A supplementation in iodine-deficient African children decreases thyrotropin stimulation of the thyroid and reduces the goiter rate1,2,3 and..... am being treated with Bexarotene and my thyroid stopped working. What is going on? Bexarotene is a synthetic retinoid X receptor (RXR)-selective retinoid used in the treatment of cutaneous T-cell lymphoma. Bexarotene causes hypothyroidism by reducing levels of both thyroid-stimulating hormone (TSH) and thyroxine, and treatment may require relatively high levels of thyroxine. See Etiology, diagnosis, and treatment recommendations for central hypothyroidism associated with bexarotene therapy for cutaneous T-cell lymphoma. Clin Lymphoma. 2003 Mar;3(4):249-52. and..... Effects of retinoids on iodine metabolism, thyroid peroxidase gene expression, and deoxyribonucleic acid synthesis in porcine thyroid cells in culture. Arai M1, Tsushima T, Isozaki O, Shizume K, Emoto N, Demura H, Miyakawa M, Onoda N. Author information Abstract Effects of retinoids on DNA synthesis, iodine metabolism, and thyroid peroxidase messenger RNA levels were studied in cultured porcine thyroid cells. Retinol (10(-8)-10(-5) M) alone did not affect DNA synthesis but potentiated that induced by epidermal growth factor or insulin-like growth factor-I without changes in the number or affinity of receptors for the growth factors, suggesting that retinol stimulates postreceptor events responsible for DNA synthesis. Retinol was an inhibitor of TSH-stimulated iodine metabolism. Iodide uptake and release of organified iodine stimulated by TSH or forskolin were inhibited dose dependently by treatment with retinol. The inhibition was detected at 10(-8) M and was approximately 50% at 10(-6) M. The potency of retinoic acid was comparable to that of retinol. The inhibitory effect of retinol was detected after treatments of thyroid cells for 24 h, and the maximal effect occurred after 48 h incubation. The cAMP accumulation in cultures treated with TSH plus retinol was lower than that of control cultures treated with TSH alone. However, iodide uptake stimulated by 8-bromo-cAMP was also inhibited by retinoids. Retinol reduced TSH- or 8-bromo-cAMP-stimulated gene expression of thyroid peroxidase. Thus, the data suggest that retinoids inhibit TSH-stimulated iodine metabolism by reducing cAMP accumulation and also by acting on the steps subsequent to cAMP production.
  9. Repairing the long-term damage from Accutane

    Support for Iodine protocol restart after accutane. https://forums.t-nation.com/t/about-the-t-replacement-category/38/2?u=ksman According to the “Textbook of Medical Physiology,” essentially all hormone receptors are dependent on iodine to some extent, which increases the sensitivity of the receptor to the hormone it is related to. For example, iodine can increase the sensitivity of insulin receptors, which is of importance for diabetes, and it can increase the sensitivity of the receptors for neurotransmitters in the brain, such as serotonin and dopamine, which affect mood and cognition. Other hormones affected by iodine concentrations include testosterone, FSH, LH and cortisol. anecdote: KSman wrote: But why do we worry about these things in a TRT context? Both hypothyroidism and adrenal fatigue undermine your metabolic capacity. TRT often restores one's metabolism to a youthful state. However, if your adrenals and thyroid levels cannot support that restored metabolic state, you hit the wall, crash or whatever you want to call it. In these cases, guys go on TRT and do not do as well as they should, or simply feel unwell or worse than before they started TRT. So TRT finds these weak links, and surprise! Doctors do not get understand this. So again, you need to be the expert and find a doctor who is not an idiot. http://www.ijdvl.com/article.asp?issn=0378-6323;year=2016;volume=82;issue=5;spage=587;epage=588;aulast=Uyar Karadag et al. initiated isotretinoin 0.5–0.75 mg/kg in 47 acne patients. They found that levels of free triiodothyronine, thyroid stimulating hormone and thyroid stimulating hormone receptor antibody decreased significantly at 3 months of isotretinoin therapy. Karadag et al. stated that there were no significant changes in the levels of thyroglobulin, antithyroglobulin or anti-thyroid peroxidase after commencing isotretinoin treatment.[7] In contrast to the above studies, our study revealed a statistically significant increase in thyroid-stimulating hormone (P = 0.018).Several studies have indicated that isotretinoin and other retinoids affect cell cycle progression, differentiation, apoptosis and cell survival in a variety of cell types.[19],[20],[21],[22],[23],[24],[25] Interestingly, isotretinoin treatment of mice results in both decreased hippocampal neurogenesis and a reduction in the hippocampal volume.[23],[24] The reason for the increase in thyroid stimulating hormone observed in our study may be a reduction in thyroid volume as a result of the direct apoptotic effect of isotretinoin on the thyroid cells. Isotretinoin is known to increase iodine uptake in thyroid cancers, facilitating therapy.[26],[27],[28] This effect may also have induced volume reduction in the thyroid gland. As a result of the reduction in thyroid volume, free triiodothyronine and free thyroxine levels may have decreased and thyroid stimulating hormone level may have increased.We enrolled patients with normal thyroid function. None of the patients experienced clinical symptoms of hypothyroidism such as increased sensitivity to cold, unexplained weight gain, puffy face, hoarseness, thinning hair, slowed heart rate or impaired memory after isotretinoin therapy for 4 months. Some of the symptoms were ignored because they might also occur as a result of isotretinoin treatment such as fatigue, dry skin, depression, muscle weakness, elevated blood cholesterol level, muscle aches, tenderness and stiffness and constipation. However, drug usage in patients who have thyroid dysfunction or are clinically hypothyroid may worsen metabolic pathology and induce irreversible hypothyroidism.The major limitation of this study is the lack of follow-up data after the cessation of isotretinoin therapy. Another limitation is that we could not analyze men and women separately.In conclusion, the increasing number of studies assessing the effects of isotretinoin on the thyroid gland will help clinicians to predict its side effects and to plan treatment accordingly. The next step in generating such data could possibly be expanding our study to include more patients and a longer follow-up.
  10. Repairing the long-term damage from Accutane

    accutane shuts off the sebaceous glands by TBI? if it doesnt, youre just treating symptoms imo.
  11. Repairing the long-term damage from Accutane

    http://forums.phoenixrising.me/index.php?threads/roaccutane-caused-depression-isotretinoin.12117/ The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl group donor in the conversion of homocysteine to methionine. In rats, experimental riboflavin deficiency is associated with low MTHFR activity and reduced levels of 5-methyltetrahydrofolate. In humans, reduced enzyme activity caused by the commonly occurring 677C→T substitution of the MTHFR gene is associated with elevated plasma homocysteine. Maybe our bodies cant convert folate to its active form to downregulate GNMT because of a riboflavin def Maybe people wth the MTHFR 677CT polymorphism are more prone to long term side effects? Maybe accutane depletes something like riboflavin (FAD) and thiamine (NADPH) that are needed for MTHFR to even work correctly? I wish richvank was still alive. he quotes: Glutathione (oxidized): This is a measurement of the concentrationof the oxidized form of glutathione (abbreviated GSSG) in the bloodplasma. The reference range is 0.16 to 0.50 micromoles per liter. Normally, oxidized glutathione in the cells is recycled back to reduced glutathione by glutathione reductase, an enzyme that requires vitamin B2 and NADPH. If this reaction is overwhelmed by oxidative stress, the cells export excess GSSG to the plasma. In some (but not all) PWCs, GSSG is elevated above the normalrange, and this represents oxidative stress. It is more common in CFS to see this level in the high-normal range. This value may increase slightly under initial treatment of a partial methylation cycle block.* ..... anecdotally one person said they spontaneously cured themselves from finasteride with these supplements. they contain folate and riboflavin. riboflavin is an aromatase inhibitor riboflavin is a 5AR inhibitor as well http://propeciahelp.com/forum/viewtopic.php?f=1&t=11457
  12. Repairing the long-term damage from Accutane

    B2 + sunlight? thioredoxin reductase cofactors and/or inducers? sulforaphane and selenium riboflavin, thiamine https://academic.oup.com/carcin/article/24/3/497/2608435/Synergy-between-sulforaphane-and-selenium-in-the 13-cis-retinoic acid covalently binds to thioredoxin reductase in human keratinocytes. 13-cis-Retinoic acid is a stereospecific suicide inhibitor of thioredoxin reductase. [3H]-labeled 13-cis-retinoic acid has been used to covalently label thioredoxin reductase in human keratinocytes. The acid-soluble cytosol fraction of human keratinocytes contained three radioactive proteins labeled by the addition of high-specific-activity [3H]-13-cis-retinoic acid to cell cultures. One of these proteins was identified as cytosolic keratinocyte thioredoxin reductase by fast-protein liquid chromatography and SDS-gel radioautography. The inhibition of thioredoxin reductase by 13-cis-retinoic acid may explain the known cytostatic and teratogenic properties attributed to this retinoid. https://www.ncbi.nlm.nih.gov/pubmed/2064786 some people develop TMAU(fish odor) after accutane . this is controlled by the flavin FMO3 hmmmm. more riboflavin http://www.curezone.org/forums/am.asp?i=2217022 http://raredisorders.imedpub.com/isotretinoin-trimethylaminuria-and-theinternet.pdf https://answers.yahoo.com/question/index?qid=20140429215524AAfvQCV Selenium ameliorates isotretinoin-induced liver injury and dyslipidemia via antioxidant effect in rats. https://www.ncbi.nlm.nih.gov/pubmed/24966012 Riboflavin is a vitamin but not at all harmless. It is therefore not surprising that riboflavin and the riboflavinogenic coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) play a role in many fields of practical medicine. Here we report on new developments in medical flavinology focusing on the assessment of riboflavin status, medical interventions based on flavins, and current medical aspects concerning the enzymes glutathione reductase (GR) and thioredoxin reductase (TrxR) as representatives of a large family of homodimeric flavoproteins. For systematic and more specific information—particularly on the clinical aspects—we should like to refer the reader to comprehensive reviews (1–4). This article cannot deal with one specific method. However, methodological details of special medical interest are included. We will keep recalling a simple rule that is often broken in practical medicine and in medical research: Drugs, B2 and light? The treatment can’t be right. It implies that flavins are readily photodegraded, and that a whole range of drugs (5,6) but also biological macromolecules (3,7,8) are subject to inactivating modification in riboflavin-dependent photoreactions. As exemplified for the cytostatic Vinca alkaloids vinblastine and vincristine as well as for the synthetic drug vindesine precautions have to be taken to prevent this side effect of riboflavin application (6). https://link.springer.com/protocol/10.1385%2F1-59259-266-X%3A229
  13. hi dose riboflavin will cure it
  14. Repairing the long-term damage from Accutane

    remember that guy who commited suicide because of his exfoliative cheilitis from accutane http://www.curezone.org/forums/fm.asp?i=2169316#i https://books.google.com/books?id=rrW11v0tNWIC&lpg=PA21&ots=wur20wphqW&dq=hormones and lios&pg=PA21#v=onepage&q&f=false
  15. Repairing the long-term damage from Accutane

    Who has been diagnosed for the MTHFR C677T mutation?
  16. Repairing the long-term damage from Accutane

    yes ... riboflavin is tied to folate metabolism and MTHFR. google that and youll come up with everything. https://www.ncbi.nlm.nih.gov/books/NBK6145/ The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a methyl group donor in the conversion of homocysteine to methionine. In rats, experimental riboflavin deficiency is associated with low MTHFR activity and reduced levels of 5-methyltetrahydrofolate. In humans, reduced enzyme activity caused by the commonly occurring 677C→T substitution of the MTHFR gene is associated with elevated plasma homocysteine. The mutant enzyme has lower affinity for its flavin cofactor than the wild-type enzyme, and recent studies show that plasma homocysteine is inversely related to riboflavin in subjects with the T-allele. This indicates that the metabolic effect of the 677C→T polymorphism is related to riboflavin status, which may have implications for future studies on the relationship between this polymorphism and various clinical and biochemical endpoints. .... https://www.researchgate.net/publication/261369157_Transcriptional_Changes_in_Organoculture_of_full_thickness_human_skin_following_topical_application_of_All-trans_Retinoic_acid holy shit look at this table. look what gets upregulated the most when topical retinoic acid is applied to the skin.... FMO! way more than CYP26 or NGAL. here they say that FMO isnt known to metabolize retinoids... but from my previous post... we know they do.
  17. Repairing the long-term damage from Accutane

    I found something that really helps with joint pain. Riboflavin 5 phosphate. which promotes FMO. cannot be regular riboflavin...must be the active form. i take 10mg a day..on day 3, and that constant joint pain is dulled 75% its tied into everything... from histamines (DAO MAO) to retinoid metabolism. ithelps the body turn b6 into active b6 which is needed for taurine. it transports copper into the cell. its also mentioned in this paper... it discusses another retinoid being metabolized by CYP2C8 and FMOs tazarotenic acid... it also shows that accutane is a substrate for this as well. it also shows when CYP2C8 is inhibited (as in the case of accutane).... FMO takes over. I think a lot of our sides are histamine related. from stomach/candida/SIBO .. all the way to joint pain. DAO and MAO enzymes being the one that are not firing. DAO cofactors = copper , b6 , C MAO cofactors = B2 FMO = flavin-containing monooxygenase http://dmd.aspetjournals.org/content/31/4/476 Inhibition experiments using paclitaxel, 9-cis-retinoic acid, 13-cis-retinoic acid and quercetin as inhibitors of CYP2C8, were conducted in a similar manner. CYP2C8 is believed to mediate the metabolism of paclitaxel (Taxol), 9-cis-retinoic acid (Panretin), and 13-cis-retinoic acid (Accutane) (Parkinson, 1996; Mugford and Kedderis, 1998; Marill et al., 2002). Quercetin is a specific inhibitor of CYP2C8 (Parkinson, 1996) Effect of Chemical Inhibition on CYP2C8-mediated Metabolism of Tazarotenic Acid. Involvement of CYP2C8 in tazarotenic acid metabolism was further confirmed by inhibition of the formation of the sulfoxide metabolite by paclitaxel, 9-cis-retinoic acid, 13-cis-retinoic acid, and quercetin. Paclitaxel, a potential CYP2C8 substrate (Parkinson, 1996) inhibited the formation of the sulfoxide metabolite from tazarotenic acid in a concentration dependent manner with an IC50of 14.9 ± 6.2 μM (Fig.6) and aKi of 30.0 ± 7.0 μM. 9-cis-retinoic acid and 13-cis-retinoic acid, both potential CYP2C8 substrates (Mugford and Kedderis, 1998; Marill et al., 2002) inhibited the formation of the sulfoxide metabolite from tazarotenic acid in a concentration-dependent manner. The i value for the potential 13-cis-retinoic acid (Accutane)-tazarotenic acid interaction is between 0.0178 and 0.0474. The potential fractional inhibition on tazarotenic acid metabolism by the dietary flavonoid, quercetin is between 0.00108 and 0.0207. However, the present study demonstrates that the metabolism of tazarotenic acid to the sulfoxide metabolite is mediated by two different enzymes, namely, CYP2C8 and FMO. Potentially, if one metabolic pathway is inhibited the alternative pathway can mediate the metabolism of tazarotenic acid. The results of this study demonstrate that both CYP2C8 and FMO enzymes are responsible for the metabolism of tazarotenic acid in humans. http://thosewithvisualsnow.yuku.com/topic/7745/discussion-Dr-Weatherall-leading-visual-snow-expert-U#.WKXddzsrKUk also interesting.... The nutrient helps convert carbohydrate into energy, which is required by all human body processes. The nutrient has an auxiliary role in the conversion or secretion of other vitamins. For instance Vitamin A is not changed into retinoic acid if certain derivatives of riboflavin are not present. Retinoic Acid is the form of Vitamin A with the most benefits. Riboflavin also helps in the absorption of Iron, and other B vitamins including folic acid and vitamins B1, B3, and B6. Flavins' role in the retina is emphasized by their high concentration (48 ± 1.7 pmol/mg−1), which is ∼20-fold higher than in the blood (2.57 ± 0.31 pmol/mg−1) (11). Said et al. (41) showed that cultured human RPE cells (ARPE-19) uptake riboflavin via a Ca2+-calmodulin-regulated process. It is not known how the retina in general and specifically the photoreceptor cells acquire flavins. Flavins are key cofactors involved in fatty acid oxidation and citric acid cycle (42). However, these processes alone may not account for the high levels of flavins found in the retina. Despite their high levels in the retina, their concentration must be tightly regulated because riboflavin deficiency (ariboflavinosis) results in photosensitivity and poor dim light vision (43, 44), although excess dietary riboflavin causes photoreceptor cell death via OS lipid peroxidation (45). Besides their role in energy metabolism, flavins likely play other yet uncharacterized roles in retinal function and/or homeostasis. It is known that flavins are cofactors in many isomerization reactions (42). For instance, FAD is the cofactor used by xanthine oxidase in the conversion of retinol to retinoic acid (46–48). Interestingly, this flavoprotein is localized to cone OSs in the human photoreceptor layer (49). FAD is also present in the blue light cryptochromes, which help mediate circadian rhythm in the inner neural retina (50–52). Despite the absence of Retb from cones, the diversity of these two processes is a good example of how widely flavoproteins are used in the retina. riboflavin in intracellular oxidation. Riboflavin deficiency is characterized by photophobia and dimness of vision at a distance and in dim light; cheilosis,
  18. Repairing the long-term damage from Accutane

    Destruction of hippocampus neurons and overall hippocampus size is implicated in accutanes depression and suicidal thoughts. How the PI3K/AKT pathway saves hippocampal neurons... The main findings of this study are as follows: (1) the expression of pAkt increased markedly in the hippocampus neurons of rats after experimental SAH, and the experimental SAH in this model induced obvious neuronal apoptosis; (2) administration of IGF-1, the agonist of the PI3K-Akt pathway, increased the expression of pAkt remarkably and alleviated neuronal apoptosis significantly in rat hippocampi after experimental SAH; (3) Ly294002, the inhibitor of the PI3K-Akt pathway, decreased the expression of pAkt and aggravated neuronal apoptosis in the hippocampus after SAH. These findings indicate that the neuronal apoptosis in this model of experimental SAH in rats could be alleviated with the activation of the PI3K-Akt pathway and aggravated with its blockage. Hence, the PI3K-Akt pathway may play a crucial role in neuronal apoptosis after SAH, and its activation may reduce the severity of secondary brain injury following experimental SAH. http://www.annclinlabsci.org/content/41/4/364.full you can cross reference PI3K/AKT with cholestasis as well.... Peony(paeoniflorin is used in Chinese medicine for cholestasis.... Paeoniflorin ameliorates ANIT‐induced cholestasis by activating Nrf2 through an PI3K/Akt‐dependent pathway in rats : PTR https://pubag.nal.usda.gov/pubag/article.xhtml?id=4569066&searchText=author%3A"Jiabo+Wang"&searchField=
  19. Repairing the long-term damage from Accutane

    so many things are inter-related here. i believe there is something acting on the FOXO for sure... be it stored in the liver, or in the adipose tissues... or micro amounts stuck to the skin receptors. i think the main thing is to make sure its bio-available copper. maybe the zinc with keep the retinol bound to RBP. maybe a cocktail. eat a shit ton of cashews...sesame seeds... something with a higher amount of copper than zinc. get it in the circulation and then bind it or destroy it... taurine...vitamin D etc the very end of this video is what we need to do... so our cells stop getting destroyed. Cu also stimulate the RAS pathway A Novel Role for Copper in Ras/Mitogen-Activated Protein Kinase Signaling http://mcb.asm.org/content/32/7/1284.full
  20. Repairing the long-term damage from Accutane

    Accutane = FOXO in the nucleus causing all of the epigenetic problems Our goal is to get FOXO OUT of the nucleus. you can do this by promoting IGF-1 or Insulin..... eat a tub of ice cream... shoot some hormones or peptides that promote IGF-1.... ONLY 3 minerals are capable of promoting PI3k/AKT they are copper, zinc or cadmium... with CU+2 being the most potent. copper also has that inverse relationship with vitamin A in the liver. it raises the serum retinol, while lowering the liver esters. These two pictures are almost scary....
  21. Repairing the long-term damage from Accutane

    If the FOX01 theory on accutane is correct.... inducing the IGF1- PI3k/AKT pathway to remove the FOX01 from the nucleus would alleviate all of the androgen problems...5AR DHT etc. These data imply that isotretinoin treatment may downregulate the transcriptional activity of AR by increasing the nuclear concentration of the AR cosuppressor FoxO1. Furthermore, the isotretinoin-induced decrease of IGF-1 serum levels may impair IGF-1/PI3K/Akt-mediated nuclear export of FoxO1. Moreover, IGF-1 is regarded as an androgen-dependent stimulator of 5α-reductase activity.38 In fact, experimental evidence has been provided for decreased androgen 5α-reduction in skin and liver of men with severe acne after oral isotretnoin treatment.39 The isotretinoin-induced decrease of IGF-1 may reduce the conversion of less potent testosterone to the more potent dihydrotestosterone (DHT), thereby decreasing the activity status of the AR ligand binding domain, which binds DHT 10 times stronger than testosterone. Free bioactive IGF-1 is controlled by IGF binding proteins (IGFBPs). In human dermal papilla cells, ATRA induced a significant increase of IGFBP-3,40 which reduced the bioavailability of free IGF-1 for IGF-1/IGF1R-signaling with potential impact on nuclear FoxO1 import vs. Modulation of FoxO signaling in human hepatoma cells by exposure to copper or zinc ions. Walter PL1, Kampkötter A, Eckers A, Barthel A, Schmoll D, Sies H, Klotz LO. Author information Abstract Cells respond to heavy metal stress by activating signaling cascades regulating cellular proliferation and survival. We here demonstrate that the anti-apoptotic kinase Akt is activated in HepG2 human hepatoma cells exposed to copper or zinc ions. Cu2+- and Zn2+-induced phosphorylation of Akt was blocked by phosphoinositide 3-kinase (PI3K) inhibitors, wortmannin and LY294002. Moreover, several endogenous Akt substrates were phosphorylated, including glycogen synthase kinase-3 and transcription factors of the FoxO family, FoxO1a and FoxO4. Exposure to Cu2+ or Zn2+ elicited the subcellular redistribution of an overexpressed FoxO1a-EGFP fusion protein from nucleus to cytoplasm, which was not seen with a mutant FoxO1a form devoid of Akt phosphorylation sites. Both FoxO phosphorylation and nuclear exclusion were blocked by wortmannin. Likewise, the subcellular translocation from nucleus to cytoplasm of the Caenorhabditis elegans FoxO ortholog, DAF-16, was caused in starved worms exposed to copper ions. Activity of the promoter of the human glucose 6-phosphatase gene, known to be regulated by insulin and FoxO1a, was demonstrated in reporter gene assays to be attenuated in hepatoma cells exposed to Cu2+. However, this suppression of glucose 6-phosphatase promoter activity was independent of modulation of the PI3K/Akt pathway. In summary, the PI3K/Akt pathway is activated in human hepatoma cells exposed to Cu2+ or Zn2+, resulting in the phosphorylation and subcellular relocalisation of transcription factor FoxO1a. Furthermore, copper is demonstrated to exert an insulin-mimetic effect also independently of the PI3K/Akt/FoxO pathway. READ THIS SENTENCE, then look at the picture above...... Exposure to Cu2+ or Zn2+ elicited the subcellular redistribution of an overexpressed FoxO1a-EGFP fusion protein from nucleus to cytoplasm https://www.ncbi.nlm.nih.gov/pubmed/16973122 Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species. https://www.ncbi.nlm.nih.gov/pubmed/11795876 Stimulation of phosphoinositide 3-kinase/Akt signaling by copper and zinc ions: mechanisms and consequences. https://www.ncbi.nlm.nih.gov/pubmed/17509519 Insulin-like modulation of Akt/FoxO signaling by copper ions is independent of insulin receptor. https://www.ncbi.nlm.nih.gov/pubmed/24933099
  22. Repairing the long-term damage from Accutane

    High dose Glycine was recommended as an upregulated GNMT would use up available glycine. ... but ive tried that with no results we know for sure accutane alters the SAM/SAH ratio raising SAH http://www.mdpi.com/1422-0067/15/5/8004/pdf GNMT SAM/SAH ratio and copper.... this paper shows hi copper liver levels also raise SAH.... but if you read closely... a cu deficiency also raises SAH Interestingly, Bethin et al. showed that Cu deficiency was also associated with 45% reduction of Ahcy hepatic levels [26], a finding that is similar to our results in fetal tx-j livers and that indicates that Cu metabolism must be strictly regulated to ensure stable Ahcy levels. Others showed that Ahcy deficiency in a 26-year-old man was associated with myopathy and developmental delay.
  23. Repairing the long-term damage from Accutane

    that is an unbelievably high amount. your post closely mimics this protocol for testosterone. https://www.scribd.com/doc/222400050/The-Secret-That-Doubles-Testosterone did you skin become oily again? wounds heal faster etc?
  24. Repairing the long-term damage from Accutane

    I had this exact reaction. One pill of CLA , and my face started stinging because of the dryness!!! the dumping of retinols makes sense...and further confirms a retinol problem. copper is antagonistic in the liver with retinol boron raises serum copper and ceruloplasmin Vitamin D detroys retinol. taurine binds retinol for excretion. I still believe we have to mobilize it from the liver (but also REPLACE IT, so it just doesnt circulate back and get stored again) . the copper will mobilize and replace it in the liver.
  25. Repairing the long-term damage from Accutane

    https://www.scribd.com/doc/222400050/The-Secret-That-Doubles-Testosterone