4029 replies to this topic

[BieraK]

Hello Guys...Just an update on my test with Methylene Blue and LLLT.

As I said before I was experimenting with these LLLT+MB, I've found that the effects from MB before LLLT are different from MB after LLLT.

Well, I have some pains in one leg, in the side of the knee and in lower part of the leg, this is not 24/7 but somestimes I've it for an entire day or for two, three days, and sometimes I don't feel it in the entire day. The first times that I used LLLT in that zone LLLT worked well for me, the pain was gone and I was very happy (the pain is no too much for now but I think that if I don't do nothing now in the future if I'm alive then it will be uncomfortable unpleasant).

The problem is that LLLT stoped worked well, the lasts sessions of LLLT alone, it gives me a burning and heat sensation, I think that this will be too much ROS and too much Nitric Oxide, or too much HIF-1alpha not counteracted... I need 23andmed or another genetic test to dyscard hypothesis.

Well here comes the interesting part of this, tonight a did a session of LLLT on my leg, 30 seconds in some areas and 45 seconds in other areas, then I waited 3 minutes and took a low dose of methylene blue, that was 100-150 mcg approximalety....

Well after some minutes I began to feel a very different sensation compared to the normal LLLT effects alone, this was a pleaseant sensation of calming, this was like a slight feeling of anesthesia... I was able to feel my leg but at the same time I was able to feel the touch less uncomfortable, and today I've no sign pain in my leg ... and the apparently therapeutic effect still remains.

I was in my home with a friend that have some pain in the back of the knee... so after my experience she do the same, 30 seconds of LLLT and 100-150 mcg of Methylene Blue, she felt a similar effect compared to me, I asked her if the effect was pleasent or unpleaseant and the reply was: A very pleasant effect of numbness.

Really I hope that this can be replicated , this look really interesting, like a really good painkiller.

The most positive hypothesis is that LLLT+MB after LLLT can enhance the LLLT effects in a really good way.... and at the other extreme the pessimist hypothesis is that I blasted my nociceptors :o

Edited by BieraK, 02 April 2015 - 01:43 AM.

[lostfalco]

Hello Guys...Just an update on my tests with Methylene Blue and LLLT.

The most positive hypothesis is that LLLT+MB after LLLT can enhance the LLLT effects in a good way.... and at the other extreme the pessimist hypothesis is that I blasted my nociceptors :o

Very cool, BieraK. Thanks for the update. Are you using Kordon's methylene blue?

[BieraK]

 

Hello Guys...Just an update on my tests with Methylene Blue and LLLT.

The most positive hypothesis is that LLLT+MB after LLLT can enhance the LLLT effects in a good way.... and at the other extreme the pessimist hypothesis is that I blasted my nociceptors :o

Very cool, BieraK. Thanks for the update. Are you using Kordon's methylene blue?

 

No, I'm using a MB 2% that I bought from a local pharmacy.

I put 1ml of MB in 300 ml of water, and then I take 1 to 3 ml of that solution in a glass of water.

My intuition, my internal feeling tells me that the sensation from the effect of this is good, the sensations is very pleaseant.
The important thing is that the Methylene blue was administered after the LLLT, if the MB is administered before the effects are not the same.. and other important thing is to do a session with shorter duration than the usual LLLT alone.

I was very happy with effects , and I was more happy when the experience was replicated for other person in the same day... of course my rational and skeptic mind tells me that this can be an illusion and that effects can be negative.

The better place for start to test this is in foot or smal areas like an arm, hand, shoulder. I'm intrigued about the effects of this combination in the brain.

Edited by BieraK, 02 April 2015 - 01:47 AM.

[lostfalco]

Here's a picture showing acetylated histones causing open chromatin and allowing transcription factors to bind. This is what I'm currently experimenting with. 

 

1. ALCAR donates acetyl groups

2. Acetate/Resistant Starch/Triacetin donate acetyl groups

3. Lithium inhibits GSK-3 which enhances CREB activity

4. Tadalafil inhibits PDE5, increases cGMP, activates c-GKI, phosphorylates CREB, and enhances CRE mediated transcription

5. Valproate...we may be able to get away with VERY low dose valproic acid since it synergies well with lithium AND we are getting so many acetyl groups already. This could help us avoid the (nasty) side effects while still getting HDAC2 inhibition. VERY High Risk though. I'm not currently taking this but I'm thinking about it. Thankfully, it looks like HDAC2 specific inhibitors are only a few years away (as research chemicals, at least). 

 

[BieraK]

Can sildenafil be used instead of taldanafil?... Lithium and Cordyceps are on the way overseas, but these need a month or more to reach to my home.

Are you planning using all this the next day after the night LLLT session?

I will go for some Taldanafil tomorrow...if the pharmacy need a prescription then I will go for Sildenafil

Edited by BieraK, 02 April 2015 - 01:52 AM.

[lostfalco]

No, I'm using a MB 2% that I bought from a local pharmacy.

My intuition, my internal feeling tells me that the sensation from the effect of this is good, the sensations is very pleaseant.
The important thing is that the Methylene blue was administered after the LLLT, if the MB is administered before the effects are not the same.. and other important thing is to do a session with shorter duration than the usual LLLT alone.

I was very happy with effects , and I was more happy when the experience was replicated for other person in the same day... of course my rational and skeptic mind tells me that this can be an illusion and that effects can be negative.

The better place for star to test this is in foot or smal areas like an arm, hand, shoulder. I'm intrigued about the effects of this combination in the brain.

 

Nice. That sounds much better than Kordon's.

 

I definitely like the idea of administering MB after LLLT...just to be safe. The combo is untested in the scientific literature (afaik) so it's difficult to predict what the effects might be. Better to be cautious.

 

I hope it keeps working well for you. It is an intriguing combo. Thanks for the update!

[lostfalco]

Can sildenafil be used instead of taldanafil?... Lithium and Cordyceps are on the way overseas, but these need a month or more to reach to my home.

Are you planning using all this the next day after the night LLLT session?

I will go for some Taldanafil tomorrow...if the pharmacy need a prescription then I will go for Sildenafil

Yeah, sildenafil should work. You just might have to dose more frequently due to the shorter half-life. 

 

Yup...the next day. 

 

Cool. I hope one of them works well for you. =)

[BieraK]

Thank you

Well in this time I was reading about the Methylene blue, this is from wiki:

 

Combined with light

Methylene blue combined with light has been used to treat resistant plaque psoriasis,^[7] AIDS-related Kaposi's sarcoma,^[8] West Nile virus,^[9] and to inactivate staphylococcus aureus,^[10] HIV-1,^[11] Duck hepatitis B,^[12] adenovirus vectors,^[13] and hepatitis C.^[14]Phenothiazine dyes and light have been known to have virucidal properties for over 80 years.^[15] In some circumstances, the combination can cause DNA damage that may lead to cancer.^[16][17] 

Then I looked to the last references, one says this
 

http://www.ncbi.nlm....pubmed/19218330

Removal of red light minimizes methylene blue-stimulated DNA damage in oesophageal cells: implications for chromoendoscopy.
 Abstract  

Barrett's oesophagus (BO) carries an increased risk of progression to oesophageal adenocarcinoma. Chromoendoscopy with methylene blue (MB) can be used to facilitate identification of BO and target areas for biopsy. If photoexcited, MB can generate reactive oxygen species and genotoxic photodegradation products leading to DNA damage. We have previously demonstrated that levels of DNA damage are increased in BO following MB chromoendoscopy. The aim of this study was to investigate whether DNA damage, as measured by the comet assay, can be minimized during chromoendoscopy by varying MB concentration and light wavelength using an in vitro model. OE33 cells were treated with MB (0.015-15 mM) and exposed to white light (WL). Cells were also illuminated with WL fractions (580-700, 480-580, 350-480, <575, <610 and <688 nm) in the presence of MB. At clinically relevant concentrations, WL illumination of MB (15 mM) caused significant DNA damage in vitro (P < 0.001). Illumination of MB with red light (580-700 nm) also stimulated high levels of DNA damage in OE33 cells (P < 0.001). This effect was not observed with green or blue light. Filtering WL to remove red light wavelengths (>575 nm) reduced DNA damage and apoptosis to control levels in MB-treated cells. In addition, reducing the concentration of MB 10-fold markedly reduced the DNA-damaging effect of MB in vitro. The results show that photoactivation of MB by red light is responsible for the majority of DNA damage. Simple modifications to MB chromoendoscopy, such as filtering out red light from endoscopic WL or reducing MB concentration, are likely to limit DNA damage induced by the procedure.

The I used this for calculate the conversion from mM to mg/ml: http://www.meduniwie...olarityJava.htm
The molecular mass of MB is 319.85 g/mol. This gives me the next:

15 mM = 4797.75 mg/ml
0.015 mM = 4.79775 mg/ml
60 - 150 mcg compared to 4 mg and compared to 4 grams is really big difference. (Taking into account that the calculations are ok)

In the mcg range MB doesn't look dangerous, the other thing is the absorption peak from MB... Infrared light doesn't seems to react with MB like the red light. The other thing is that MB after the LLLT gives to this a better safety than MB before the LLLT.
http://upload.wikime...on_spectrum.png

However there is a clearly interaction between LLLT and MB, and I agree with you about the character of untested in the scientific literature of "Low dose" MB+Infrared Light gives to this some caution concern.

Edited by BieraK, 02 April 2015 - 02:56 AM.

[Kalliste]

Has anyone tried Hypothermia caps? I can't find a good supplier for Sweden. Heard some interesting gossip about the idea of cooling down the brain, Increasing endgenous antioxidants, autophagy and so on. Anyone who tried it? Searching the forum does not give me anything.

 

 

Resources and CCT Systems:

• The Rapunzel project is a wonderful non-profit organization that was established to help chemotherapy patients maintain their hair during treatment. They have also helped to get funding for CCT freezers. Check out their useful tips for CCT users. 
• Medscape article “Presentation, Impact and Prevention of Chemotherapy-induced Hair Loss.”
• BreastCancer.org Community Posts (type in “cold caps” in the search tab and you will find thousands of posts by people talking about cold caps)
• Penguin Cold Cap Therapy
• DigniCap CCT system 
• ChemoCap
• Elasto-Gel™ Cold Caps
• Paxman (PCS-1 and 2, Orbis)
• Amit Technology (SCSII)
• Chemocoldcaps (a full-service U.S.-based company that sells a package that includes delivery of Elasto-Gel cold caps, all the supplies and accessories you’ll need and personalized training and tips so that you will have the best outcome possible.)

 

 

 

How does it work?

Cold cap therapy (CCT) involves the use of special caps, frozen to a very cold temperature, and worn for a period of time before, during and after each intravenous chemotherapy session. Studies have shown that scalp cooling reduces the blood flow to the scalp and the metabolism of chemotherapy in the hair follicles. This results in less hair loss from chemotherapy.

Although there are many CCT systems on the market, the most commonly available cold cap system in the U.S. is called the Penguin Cold Cap. This cap is filled with gel material that is cooled down to minus 22 degrees Fahrenheit. The caps have to be changed every thirty minutes during the chemotherapy session.

Typically, the cap is worn 30-60 minutes before the start of each chemotherapy session. Then, every 30 minutes, throughout the chemotherapy infusion, a new frozen cap is placed on the head. The patient continues to reapply the frozen caps for 30 minutes (for up to 4 hours, depending on the chemotherapy regimen) after the chemotherapy infusion has completed.

 

 

Found these:

 

http://www.amazon.co...hypothermia cap

http://www.amazon.co...hypothermia cap

Attached Files

•  scalp_cooling_EN-e1360715619290.png   33.71KB   4 downloads

Edited by Cosmicalstorm, 02 April 2015 - 08:16 PM.

[middpanther88]

Here's a picture showing acetylated histones causing open chromatin and allowing transcription factors to bind. This is what I'm currently experimenting with. 

 

1. ALCAR donates acetyl groups

2. Acetate/Resistant Starch/Triacetin donate acetyl groups

3. Lithium inhibits GSK-3 which enhances CREB activity

4. Tadalafil inhibits PDE5, increases cGMP, activates c-GKI, phosphorylates CREB, and enhances CRE mediated transcription

5. Valproate...we may be able to get away with VERY low dose valproic acid since it synergies well with lithium AND we are getting so many acetyl groups already. This could help us avoid the (nasty) side effects while still getting HDAC2 inhibition. VERY High Risk though. I'm not currently taking this but I'm thinking about it. Thankfully, it looks like HDAC2 specific inhibitors are only a few years away (as research chemicals, at least). 

 

 

 

What are your current observations with what you're experimenting with?

[mettmett]

Ok so here:

http://www.anti-agin...lecules-series/

He talks about Gsk3 pathways. Excerpt:

"when GSK-3s are inhibited by compounds such as lithium, they can “bypass” the normal methods of blocking these “pro-aging pathways” and can therefore make a direct impact towards reducing aging by inhibiting the Insulin/IGF pathway and inhibiting the mTOR pathway."

Maybe I'm wrong or there is more to it, but wouldn't inhibiting igf/mtor be bad if someone was bulking and trying to gain muscle?

[lostfalco]

Nitric Oxide causes HDAC2 to release from chromatin which facilitates gene expression (in vitro). Very interesting. 

 

btw...Do NOT take nitric oxide with tadalafil. =)

 

"We recently described that HDAC2, a nuclear histone deacetylase that is highly expressed in neurons, is regulated by S-nitrosylation.1 NO generated in response to neurotrophin stimulation diffuses throughout the neuronal soma into the cell nucleus and nitrosylates HDAC2 at cysteine residues 262 and 274, releasing it from chromatin to facilitate gene expression.1,2 S-nitrosylation of HDAC2 stimulates its release from DNA but does not alter the enzyme's catalytic activity.1"

 

"Our observations indicate that NO regulates both nuclear and cytoplasmic neuronal HDACs."

 

http://www.ncbi.nlm....les/PMC2649289/

 

Commun Integr Biol. 2009;2(1):11-3.

Nitric oxide and histone deacetylases: A new relationship between old molecules.

Watson PM1, Riccio A.

Author information

Abstract

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from a range of nuclear and cytoplasmic proteins. Recently, we described a novel route to neurotrophin-dependent gene activation in neurons, which requires the S-nitrosylation of nuclear HDAC2 by the gaseous molecule nitric oxide (NO).1 We have further investigated the NO-dependent regulation of HDACs in neurons. Using a fluorogenic deacetylation assay, we show that NO decreases the enzymatic activity of a subgroup of neuronal HDACs in vitro and that this inhibition is not due to damaging modifications such as oxidation or tyrosine nitration. The neuronal HDACs whose catalytic activity is inhibited by NO are entirely those that are localized in the cytoplasm. These observations support and extend the concept that nitric oxide is a key regulator of HDAC function in mammalian neurons.

 

 

[lostfalco]

http://www.ncbi.nlm....pubmed/18754010

 

Nature. 2008 Sep 18;455(7211):411-5. doi: 10.1038/nature07238. Epub 2008 Aug 27.

S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons.

Nott A1, Watson PM, Robinson JD, Crepaldi L, Riccio A.

Author information

Abstract

Brain-derived neurotrophic factor (BDNF) and other neurotrophins have a vital role in the development of the rat and mouse nervous system by influencing the expression of many specific genes that promote differentiation, cell survival, synapse formation and, later, synaptic plasticity. Although nitric oxide (NO) is known to be an important mediator of BDNF signalling in neurons, the mechanisms by which neurotrophins influence gene expression during development and plasticity remain largely unknown. Here we show that BDNF triggers NO synthesis and S-nitrosylation of histone deacetylase 2 (HDAC2) in neurons, resulting in changes to histone modifications and gene activation. S-nitrosylation of HDAC2 occurs at Cys 262 and Cys 274 and does not affect deacetylase activity. In contrast, nitrosylation of HDAC2 induces its release from chromatin, which increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes transcription. Notably, nitrosylation of HDAC2 in embryonic cortical neurons regulates dendritic growth and branching, possibly by the activation of CREB (cyclic-AMP-responsive-element-binding protein)-dependent genes. Thus, by stimulating NO production and S-nitrosylation of HDAC2, neurotrophic factors promote chromatin remodelling and the activation of genes that are associated with neuronal development.

 

[lourdaud]

Isn't nitric oxide harmful?

[lostfalco]

Isn't nitric oxide harmful?

Hey lourdaud, as with anything it can be bad if you have too much but it also plays numerous beneficial roles as a gasotransmitter, vasodilator, immune system mediator, etc.

[BieraK]

Cistanche Tubulosa another herb for increasing cGMP:
http://www.ncbi.nlm....pubmed/19468974
 

Echinacoside elicits endothelium-dependent relaxation in rat aortic rings via an NO-cGMP pathway.

He WJ1, Fang TH, Ma X, Zhang K, Ma ZZ, Tu PF.

Author information

 

Abstract

The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinalherb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 microM) and KCl (60 mM). Echinacoside (30-300 microM) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, N(W)-nitro-L-arginine methyl ester (L-NNA, 100 microM), an unselective soluble guanylate cyclase blocker, methylene blue (10 microM), the selective sGC inhibitor 1 H-[1, 2, 4]oxadiazolo[4,3- A]quinoxalin-1-one (ODQ, 1 microM); in addition, atropine (1 microM), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 microM) had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE. These results indicate for the first time that echinacoside mediates the endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide (NO)-cGMP pathway.

Georg Thieme Verlag KG Stutt

 

[lostfalco]

Gonna be trying xanthinol nicotinate soon. Anybody tried this before? Looks very interesting (based on fairly limited studies). 

 

Apparently it enhances, "cell metabolism and oxygen supply in the brain." The hypothesis is that it works intracellularly as opposed to niacin which works primarily extracellularly. It was mainly effective in older healthy people but I'm already taking niacin so I figured it would interesting to try XN and see if I notice a difference.  

 

I ordered mine from here (no affiliation)  http://www.antiaging...cotinate-xanpro

 

http://www.ncbi.nlm..../pubmed/3936095

 

Psychopharmacology (Berl). 1985;87(4):390-5.

The effects of nicotinic acid and xanthinol nicotinate on human memory in different categories of age. A double blind study.

Loriaux SM, Deijen JB, Orlebeke JF, De Swart JH.

Abstract

The treatment effect of nicotinic acid and xanthinol nicotinate on human memory was compared with placebo in 96 healthy subjects. Forty-three subjects were young (35-45 years), 30 subjects middle aged (55-65 years) and 23 subjects were old aged (75-85 years). Pre- and post-treatment scores were measured on a battery of memory tasks, covering sensory register, short-term memory and long-term memory. The treatment regime was 1 dragee t.i.d. for 8 weeks. The administration of xanthinol nicotinate (500 mg, containing 141.7 mg nicotinic acid), nicotinic acid (141.7 mg) and placebo (lactose) was double-blind. Pre- and post-treatment scores were analysed by means of a multivariate covariance technique, the pre-treatment score serving as covariate. Nicotinic acid treatment resulted in improvement of sensory register and short-term memory, while xanthinol nicotinate improved sensory register, short-term memory and long-term memory. In comparison with placebo, both active compounds yielded improvements of 10-40%, depending on type of task. Treatment effects of nicotinic acid were predominantly found in the young and middle-aged, whereas treatment effects of xanthinol nicotinate were predominantly found in the old. These results are interpreted by the supposed activity of nicotinic acid at the cell membrane, improving neuronal transmission, and of xanthinol nicotinate inside the cell, enhancing cell metabolism and oxygen supply in the brain.

 

Edited by lostfalco, 11 April 2015 - 10:19 PM.

[lostfalco]

A Quick Update: I will most likely be getting back to testing ICES within the next month or so. I'm currently working on an absurdly massive stack that combines PDE4i, PDE5i, nitric oxide enhancement, GSK-3i, HDACi, acetyl groups, ATP enhancement, kynurenic acid inhibition, and neural cell adhesion molecule enhancement. I've been jokingly calling it "The God Stack." If I live...I'll let you guys know how it goes. =)  

 

 

 

 

 

 

Edited by lostfalco, 11 April 2015 - 10:54 PM.

[mettmett]

I'm already a fan of niacin and xanthinol nicotinate seems even better. I will definitely be buying some in the near future.  I've currently paused my tadalifil usage because I came close to getting a nosebleed a couple times - which isn't normal for me.  So I'm seeing if they were connected or just coincidence.

Good luck on your "god stack" falco, seems pretty awesome! 
 

[lostfalco]

Sounds good, mettmett. Let me know when you try XN. Most of the anecdotes online have been really positive...but you never know.

[lostfalco]

This is one of the coolest mechanisms of potential enhancement that I've come across in a while...mRNA modulation. In C Elegans a protein called musashi actively breaks down memories. Musashi binds to mRNA's related to Arp2/3 and downregulates memory related translation. Therefore, if you inhibit musashi then it is possible that memories will persist for a much longer period of time. Will this work in humans? Not sure.

 

As it turns out, oleic acid (olive oil, avocado oil, etc.) inhibits musashi as do a couple of other omega 9 fatty acids. (see second study below) Oleic acid binds to musashi, changes musashi's conformation, and prevents it from binding to mRNA. 

 

This is all related to the actin cytoskeleton and microtubules and the role that they play in learning and memory. This is potentially huge and I will be discussing this further as I move forward with The God Stack.

 

http://www.ncbi.nlm....pubmed/24630719

 

Cell. 2014 Mar 13;156(6):1153-66. doi: 10.1016/j.cell.2014.01.054.

Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex.

Hadziselimovic N1, Vukojevic V1, Peter F1, Milnik A2, Fastenrath M3, Fenyves BG4, Hieber P1, Demougin P1, Vogler C5, de Quervain DJ6, Papassotiropoulos A7, Stetak A8.

Author information

Abstract

A plastic nervous system requires the ability not only to acquire and store but also to forget. Here, we report that musashi (msi-1) is necessary for time-dependent memory loss in C. elegans. Tissue-specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-binding protein immunoprecipitation (IP), we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2, and ARX-3 translation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning-induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.

 

http://www.ncbi.nlm....les/PMC4094780/

 

Elife. 2014 Jun 16;3. doi: 10.7554/eLife.02848.

Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite.

Clingman CC1, Deveau LM1, Hay SA1, Genga RM1, Shandilya SM1, Massi F1, Ryder SP1.

Author information

Abstract

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon ω-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA association. Musashi proteins are critical for development of the brain, blood, and epithelium. We identify stearoyl-CoA desaturase-1 as a MSI1 target, revealing a feedback loop between ω-9 fatty acid biosynthesis and MSI1 activity. We propose that other RRM proteins could act as metabolite sensors to couple gene expression changes to physiological state.

 

Humans have a musashi gene. http://www.ncbi.nlm.nih.gov/gene/4440

 

 

Edited by lostfalco, 12 April 2015 - 10:46 PM.

[Kalliste]

My 808nm 200mW laser from Ebay arrived today. It was supposed to be focusable but I have been unable to change the shape of it from a small rectangle. I also bought 808nm protective glasses that makes the laser-rectangle invisible.

 

Any suggestions for how to proceed.

[lostfalco]

mRNA moving in brain cells in real time. Frickin' cool. 

 

[Kalliste]

My 808nm 200mW laser from Ebay arrived today. It was supposed to be focusable but I have been unable to change the shape of it from a small rectangle. I also bought 808nm protective glasses that makes the laser-rectangle invisible.

 

Any suggestions for how to proceed.

 

The laser feels good just holding it to my skin. I can only cover small areas for a few minutes before it gets warm. I've begun with my head. I'm currently on the third day of a faste so I can't say there were any fireworks. I did have vivid dreams tonight after a session before going to bed. I will update here in a few weeks.

[lostfalco]

This post is extremely speculative on my part and requires a significant amount of additional fact checking (aka I'm making A LOT of assumptions that could very well be wrong)...but I'm short on time and thought I would share anyway. =)

 

"We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1 (musashi)." http://www.ncbi.nlm....pubmed/24630719

 

So, activating adducin and inhibiting musashi might have a synergistic effect on retaining (not acquiring) memories. Adducin is activated by rho-kinase and rho-kinase is activated by arachidonic acid. Therefore, take arachidonic acid (not too much) to enhance adducin. Additionally, DHA synergizes extremely well with arachidonic acid and has been shown to enhance memory in humans. 

 

Egg yolks, chicken, and organ meats are good sources of arachidonic acid. It is also sold online as a supplement. 

 

To sum up:

1. Oleic Acid (olive oil) inhibits musashi

2. Arachidonic Acid enhances adducin

3. DHA combines well with Arachidonic Acid

4. Boswellia prevents the breakdown of Arachidonic Acid into its inflammatory metabolites.  

 

**Note: some studies have indicated that arachidonic acid causes significant inflammation but there is disagreement on this. Check out the research and decide if it's something you're interested in testing out. =) Most of us probably get a decent amount from our diet as well so supplementation may be unnecessary. 

 

http://www.ncbi.nlm....pubmed/22307086

 

EMBO J. 2012 Mar 21;31(6):1453-66. doi: 10.1038/emboj.2012.14. Epub 2012 Feb 3.

A role for α-adducin (ADD-1) in nematode and human memory.

Vukojevic V1, Gschwind L, Vogler C, Demougin P, de Quervain DJ, Papassotiropoulos A, Stetak A.

Author information

Abstract

Identifying molecular mechanisms that underlie learning and memory is one of the major challenges in neuroscience. Taken the advantages of the nematode Caenorhabditis elegans, we investigated α-adducin (add-1) in aversive olfactory associative learning and memory. Loss of add-1 function selectively impaired short- and long-term memory without causing acquisition, sensory, or motor deficits. We showed that α-adducin is required for consolidation of synaptic plasticity, for sustained synaptic increase of AMPA-type glutamate receptor (GLR-1) content and altered GLR-1 turnover dynamics. ADD-1, in a splice-form- and tissue-specific manner, controlled the storage of memories presumably through actin-capping activity. In support of the C. elegans results, genetic variability of the human ADD1 gene was significantly associated with episodic memory performance in healthy young subjects. Finally, human ADD1 expression in nematodes restored loss of C. elegans add-1 gene function. Taken together, our findings support a role for α-adducin in memory from nematodes to humans. Studying the molecular and genetic underpinnings of memory across distinct species may be helpful in the development of novel strategies to treat memory-related diseases.

 

http://www.ncbi.nlm....pubmed/10209029

 

J Cell Biol. 1999 Apr 19;145(2):347-61.

Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility.

Fukata Y1, Oshiro N, Kinoshita N, Kawano Y, Matsuoka Y, Bennett V, Matsuura Y, Kaibuchi K.

Author information

Abstract

Adducin is a membrane skeletal protein that binds to actin filaments (F-actin) and thereby promotes the association of spectrin with F-actin to form a spectrin-actin meshwork beneath plasma membranes such as ruffling membranes. Rho-associated kinase (Rho- kinase), which is activated by the small guanosine triphosphatase Rho, phosphorylates alpha-adducin and thereby enhances the F-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by Rho-kinase as Thr445 and Thr480. We prepared antibody that specifically recognized alpha-adducin phosphorylated at Thr445, and found by use of this antibody that Rho-kinase phosphorylated alpha-adducin at Thr445 in COS7 cells in a Rho-dependent manner. Phosphorylated alpha-adducin accumulated in the membrane ruffling area of Madin-Darby canine kidney (MDCK) epithelial cells and the leading edge of scattering cells during the action of tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF). The microinjection of Botulinum C3 ADP-ribosyl-transferase, dominant negative Rho-kinase, or alpha-adducinT445A,T480A (substitution of Thr445 and Thr480 by Ala) inhibited the TPA-induced membrane ruffling in MDCK cells and wound-induced migration in NRK49F cells. alpha-AdducinT445D,T480D (substitution of Thr445 and Thr480 by Asp), but not alpha-adducinT445A,T480A, counteracted the inhibitory effect of the dominant negative Rho-kinase on the TPA-induced membrane ruffling in MDCK cells. Taken together, these results indicate that Rho-kinase phosphorylates alpha-adducin downstream of Rho in vivo, and that the phosphorylation of adducin by Rho-kinase plays a crucial role in the regulation of membrane ruffling and cell motility.

 

http://www.ncbi.nlm....pubmed/11294240

 

Pflugers Arch. 2001 Feb;441(5):596-603.

Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase.

Araki S1, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T.

Author information

Abstract

Arachidonic acid activates isolated Rho-kinase and contracts permeabilized smooth muscle fibres. Various assays were carried out to examine the mechanism of this activation. Native Rho-kinase was activated 5-6 times by arachidonic acid but an N-terminal, constitutively-active fragment of Rho-kinase, expressed as a glutathione-S-transferase (GST) fusion protein and including the catalytic subunit (GST-Rho-kinase-CAT), was not. GST-Rho-kinase-CAT was inhibited by a C-terminal fragment of Rho-kinase and arachidonic acid removed this inhibition. These results suggest that the C-terminal part of Rho-kinase, containing the RhoA binding site and the pleckstrin homology domain, acts as an autoinhibitor. It is suggested further that activation by arachidonic acid is due to its binding to the autoinhibitory region and subsequent release from the catalytic site. Arachidonic acid, at concentrations greater than 30 microM, increases force in alpha-toxin-permeabilized femoral artery but not in Triton X-100-skinned fibres. The content of Rho-kinase in the latter was lower than in alpha-toxin-treated or intact fibres. The arachidonic acid-induced contraction was not observed at a pCa above 8.0 and was inhibited by Y-27632 and wortmannin, inhibitors of Rho-kinase and myosin light-chain kinase (MLCK), respectively. The activation of Rho-kinase and subsequent phosphorylation of the myosin phosphatase target subunit inhibits myosin phosphatase and increases myosin phosphorylation.

 

http://www.ncbi.nlm....pubmed/16905216

 

Neurosci Res. 2006 Oct;56(2):159-64. Epub 2006 Aug 14.

Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction.

Kotani S1, Sakaguchi E, Warashina S, Matsukawa N, Ishikura Y, Kiso Y, Sakakibara M, Yoshimoto T, Guo J, Yamashima T.

Author information

Abstract

Age-dependent increase of peroxidation of membrane fatty acids such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) in neurons was reported to cause a decline of the hippocampal long-term potentiation (LTP) and cognitive dysfunction in rodents. Although supplementation of ARA and DHA can improve LTP and cognitive function in rodents, their effects in humans are unknown. The present work was undertaken to study whether ARA and DHA have beneficial effects in human amnesic patients. The subjects were 21 mild cognitive dysfunction (12 MCI-A with supplementation and 9 MIC-P with placebo), 10 organic brain lesions (organic), and 8 Alzheimer's disease (AD). The cognitive functions were evaluated using Japanese version of repeatable battery for assessment of neuropsychological status (RBANS) at two time points: before and 90 days after the supplementation of 240 mg/day ARA and DHA, or 240 mg/day of olive oil, respectively. MCI-A group showed a significant improvement of the immediate memory and attention score. In addition, organic group showed a significant improvement of immediate and delayed memories. However, there were no significant improvements of each score in AD and MCI-P groups. It is suggested from these data that ARA and DHA supplementation can improve the cognitive dysfunction due to organic brain damages or aging.

 

 

 

Edited by lostfalco, 15 April 2015 - 02:52 PM.

[lostfalco]

Pictures illustrating the roles of adducin, musashi, actin, etc. in causing synapses to grow. Larger synapses = greater memory. 

 

 

 

 

 

 

 

Edited by lostfalco, 15 April 2015 - 02:44 PM.

[lostfalco]

Sorry about all the pics. =) Just one more. This one shows the relationship between microtubules and actin in dendrites. 

 

[BigPapaChakra]

WIth DHA, it would make sense to use forms in the sn-2 glycerol position as they are incorporated into neural lipid structures more readily; I've heard good things about this: http://mawulf.com/wh...hc_location=ufiwhich is DHA-ethyl ester (EE). This is purportedly a good source of it, free from contaminants: http://www.iherb.com/Doctor-s-Best-Best-DHA-500-from-Calamari-500-mg-180-Softgels/37105

 

The DHA contained in seafood is primarily in the sn-2 position (1, 2). 

 

Fresh, raw seafood seems best, as even freezing can denature DHA at the sn-2 position; it will still be effective, and it won't decrease the total amount of DHA (in the sn-2 position) a ton, but it likely can make a meaningful difference (3, 4), especially if one is consuming copious amounts or over the long haul.

 

 

(1) http://link.springer...1007/BF02531280

(2) http://link.springer...1007/BF02523923

(3) http://onlinelibrary...08.01176.x/full

(4) http://jast.modares....cle_4597_0.html

 

I generally believe that low tissue unsaturation is best, but this doesn't mean one can't consume modest amounts of DHA and AA whilst maintaining overall low tissue unsaturation (look up the work of Hulbert et al and his colleagues for studies on tissue unsaturation, longevity, metabolism, etc). Thus, I'm trying to consume a low PUFA diet though with moderately large amounts of DHA, which should also take care of AA. I'm thinking about adding in that calamari sourced DHA-EE as well. 

 

Also, as most know, the Happy Stack incorporates nucleotides in addition to DHA. Well, Dr. Benjamin Frank, MD, PhD has authored books and textbooks on the use of nucleotides and a seafood laden diet; sardines appear to be LOADED in bioavailable nucleotides: http://warddeanmd.co...-acid-part-one/(I have one of Dr. Frank's books and he includes a couple really old studies on the nucleotide content of foods and included tables from them; sardines were the highest, but pinto beans had lots as well, as did anchovies, chicken liver, and some other lentils). 

 

So, DHA-EE + when available, sushi/sashimi, eggs and liver (for AA and choline) and maybe some UMP or detoxadine...  

[BigPapaChakra]

WIth DHA, it would make sense to use forms in the sn-2 glycerol position as they are incorporated into neural lipid structures more readily; I've heard good things about this: http://mawulf.com/wh...hc_location=ufiwhich is DHA-ethyl ester (EE). This is purportedly a good source of it, free from contaminants: http://www.iherb.com/Doctor-s-Best-Best-DHA-500-from-Calamari-500-mg-180-Softgels/37105

 

The DHA contained in seafood is primarily in the sn-2 position (1, 2). 

 

Fresh, raw seafood seems best, as even freezing can denature DHA at the sn-2 position; it will still be effective, and it won't decrease the total amount of DHA (in the sn-2 position) a ton, but it likely can make a meaningful difference (3, 4), especially if one is consuming copious amounts or over the long haul.

 

 

(1) http://link.springer...1007/BF02531280

(2) http://link.springer...1007/BF02523923

(3) http://onlinelibrary...08.01176.x/full

(4) http://jast.modares....cle_4597_0.html

 

I generally believe that low tissue unsaturation is best, but this doesn't mean one can't consume modest amounts of DHA and AA whilst maintaining overall low tissue unsaturation (look up the work of Hulbert et al and his colleagues for studies on tissue unsaturation, longevity, metabolism, etc). Thus, I'm trying to consume a low PUFA diet though with moderately large amounts of DHA, which should also take care of AA. I'm thinking about adding in that calamari sourced DHA-EE as well. 

 

Also, as most know, the Happy Stack incorporates nucleotides in addition to DHA. Well, Dr. Benjamin Frank, MD, PhD has authored books and textbooks on the use of nucleotides and a seafood laden diet; sardines appear to be LOADED in bioavailable nucleotides: http://warddeanmd.co...-acid-part-one/(I have one of Dr. Frank's books and he includes a couple really old studies on the nucleotide content of foods and included tables from them; sardines were the highest, but pinto beans had lots as well, as did anchovies, chicken liver, and some other lentils). 

 

So, DHA-EE + when available, sushi/sashimi, eggs and liver (for AA and choline) and maybe some UMP or detoxadine...  

[lostfalco]

WIth DHA, it would make sense to use forms in the sn-2 glycerol position as they are incorporated into neural lipid structures more readily

Hey Papa, thanks for the info. The site that you linked to specifically indicates that DHA-EE was better for those with Peroxisomal Biogenesis Disorders which disrupts fat metabolism. Is there any evidence (studies) that it is better for those without such disorders?

 

Also, there is evidence (in cell studies) that DHA is incorporated into mitochondrial cardiolipin. How would the DHA-EE form affect it's absorption and activity in mitochondria?

 

http://www.ncbi.nlm....pubmed/25866137

 

J Nutr Biochem. 2015 Mar 26. pii: S0955-2863(15)00066-2. doi: 10.1016/j.jnutbio.2015.02.005. [Epub ahead of print]

Polyunsaturated fatty acids incorporation into cardiolipin in H9c2 cardiac myoblast.

Ting HC1, Chao YJ1, Hsu YH2.

Author information

Abstract

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), known as ω-3 polyunsaturated fatty acid (PUFA), are common nutrients in daily food intake and have been shown to prevent cardiovascular disease and improve cardiac functions. Cardiolipin is a mitochondrial phospholipid necessary for maintaining physiological function of mitochondria. Several studies have indicated that the cardiolipin acyl chain compositions affect the function of cardiolipin and mitochondria. Here, we investigated the structural changes of cardiolipin after DHA and EPA supplementation and compared them to arachidonic acid (AA) treatment. H9c2 cardiac myoblast was used as a cell model, and cardiolipin species was monitored and identified via LC-MS and MS/MS. Our results showed distinct mass envelopes of cardiolipin with the same carbon number but different double bonds in mass spectrum. There were 116 cardiolipin species with 36 distinct mass in 6 mass envelopes identified by MS/MS. Three days of PUFA treatment resulted in decreases of low-molecular-weight cardiolipin and increases of high-molecular-weight cardiolipin, suggesting the incorporation of exogenous DHA, EPA and AA into mitochondrial cardiolipin. PUFA incorporation was further verified by MS/MS analysis. More importantly, we found that DHAsupplementation elevated the percent content of less unsaturated cardiolipin species and highly unsaturated cardiolipin species, containing ω-3 fatty acyl chains, indicating a ω-3 fatty acid incorporation mechanism with peroxidation protection. Our results indicate that PUFA supplementation differentially perturbed the fatty acyl chain compositions in the mitochondrial cardiolipin in the H9c2 cardiac myoblast, suggesting that mitochondrial membrane and the function of mitochondria are susceptible to exogenous lipid species.