4029 replies to this topic

[lostfalco]

 

Also, anyone who wants to improve ghrelin the "natural way," could considering drinking Oolong Tea.

 

http://www.sciencedi...02194981500054X

 

"It is expected that more candidate compounds for ghrelin analogues should be continually identified from natural sources."

 

Very interesting. Will have to look into this. Thanks, mettmett. 

[lostfalco]

And since we're on the subject of risky research chemicals I might as well post on SR9009 and SR9011. Pharmacological modulation of clock genes is just so damn cool and sleep, the suprachiasmatic nucleus, circadian biology, etc. are essential to learning and memory. 

 

Ceretropic sells this as well. http://www.ceretropi...-9009-solution/

I've had good results over the years with 465nm light on my intrinsically photosensitive retinal ganglion cells. This the device I have. I use it in the morning and if I need to pull an all-nighter I use it at night. http://www.amazon.co.../dp/B000W8Y7FY/

 

http://www.ncbi.nlm....les/PMC4495958/

 

Nat Commun. 2014 Dec 23;5:5759. doi: 10.1038/ncomms6759.

Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour.

Banerjee S1, Wang Y2, Solt LA1, Griffett K2, Kazantzis M1, Amador A1, El-Gendy BM1, Huitron-Resendiz S3, Roberts AJ3, Shin Y1, Kamenecka TM1, Burris TP2.

Author information

Abstract

Synthetic drug-like molecules that directly modulate the activity of key clock proteins offer the potential to directly modulate the endogenous circadian rhythm and treat diseases associated with clock dysfunction. Here we demonstrate that synthetic ligands targeting a key component of the mammalian clock, the nuclear receptors REV-ERBα and β, regulate sleep architecture and emotional behaviour in mice. REV-ERB agonists induce wakefulness and reduce REM and slow-wave sleep. Interestingly, REV-ERB agonists also reduce anxiety-like behaviour. These data are consistent with increased anxiety-like behaviour of REV-ERBβ-null mice, in which REV-ERB agonists have no effect. These results indicate that pharmacological targeting of REV-ERB may lead to the development of novel therapeutics to treat sleep disorders and anxiety.

 

 

Edited by lostfalco, 10 December 2015 - 05:25 AM.

[resveratrol_guy]

 

...and the drug best targetted to treat acromegaly is pegvisomant, which hammers down IGF1, and with it, cancer risk. So I really wouldn't mess with GH unless I had exhausted all other options for neurological enhancement. But if you have a way to know how much you can safely get away with, go for it.

 

My other 2 cents, as to cold exposure, is that phosphotau development is stimulated by low body temperature. (See my post here on 7/27/2015 for context.) I always figured that hot implies high entropy, and cold implies more order, so cold must be superior for fundamental thermodynamic reasons. So much for logic; I'll stick to cooking my scalp with LLLT.

Hey resveratrol_guy, I totally understand if you want to keep IGF1 low. However, people with acromegaly usually have pituitary tumors (or tumors elsewhere) that result in extremely elevated growth hormone levels...sometimes 10 times higher than normal. We are not going to get anywhere close to that with MK-677. 

 

The study you linked on cold exposure discussed anesthesia induced hypothermia for long periods of time (at least 60 minutes in vivo). Very different than cold thermogenesis. 

 

"Anesthesia induced a progressive and drastic drop in temperature reaching ∼26°C after 60 minutes of anesthesia." 

 

"All general anesthetics induce hypothermia through the deregulation of both non- shivering and shivering thermogenesis regulation." 

 

"This hypothermia directly results in an in vivo increase of AD-related tau phospho-epitopes..."

 

http://www.nature.co...icles/srep00480

 

Do you have a study showing that cold thermogenesis causes tau hyperphosphorylation?

 

I'm with you about logic...that's why we do experiments! I've been surprised more times than I can count. 

 

LLLT (at the power density and wavelength we currently use) has a very minimal heating effect and current evidence indicates that this is not a major contributor to its effects. So, hopefully your scalp will remain uncooked. =)

 

 

I see your point about the modest effects of MK-677 as opposed to a pituitary tumor resulting in pathologically high IGF1. My point was really that IGF1 appears to be almost totally nefarious in adults who value longevity. In particular, I'm referring to this epidemiological observation. So really this was more of a general comment on why I think we want to avoid all but absolutely necessary levels of IGF1 in mature adults.

 

As to cold and phosphotau, I think you've presented a compelling argument that hypothermia due to moderate cold exposure (in the sense of chronic cold exposure which must have occurred often in our ancestors' history) is vastly smaller in magnitude than that which was demonstrated to amplify phosphotau production. Unfortunately, I have no studies to offer by way of the former, so now I suppose we're left with an annoying open question.

 

I agree with Papa's implicit assertion that, because an organism is not a closed system, its intrinsic entropy level might oscillate nonmonotonically throughout life. I was just making the point that it's thermodynamically counterintuitive that LLLT works at all -- and yeah, that's why we do experiments -- in the same sense that hormesis can facilitate therapeutic benefit from various toxins within certain dosing envelopes.
 

[lostfalco]

I see your point about the modest effects of MK-677 as opposed to a pituitary tumor resulting in pathologically high IGF1. My point was really that IGF1 appears to be almost totally nefarious in adults who value longevity. In particular, I'm referring to this epidemiological observation. So really this was more of a general comment on why I think we want to avoid all but absolutely necessary levels of IGF1 in mature adults.

 

As to cold and phosphotau, I think you've presented a compelling argument that hypothermia due to moderate cold exposure (in the sense of chronic cold exposure which must have occurred often in our ancestors' history) is vastly smaller in magnitude than that which was demonstrated to amplify phosphotau production. Unfortunately, I have no studies to offer by way of the former, so now I suppose we're left with an annoying open question.

 

I agree with Papa's implicit assertion that, because an organism is not a closed system, its intrinsic entropy level might oscillate nonmonotonically throughout life. I was just making the point that it's thermodynamically counterintuitive that LLLT works at all -- and yeah, that's why we do experiments -- in the same sense that hormesis can facilitate therapeutic benefit from various toxins within certain dosing envelopes.
 

Yeah, I totally get where you're coming from on IGF-1 (even in normal ranges)...which is why I mentioned that I completely understand the desire to keep it as low as possible. I don't really want to jump into the IGF-1/cancer debate so I'll just say that my current reading of the evidence and the results of recent experiments have led me to the profound conclusion that....it's still an open question. I'm definitely keeping an eye on the research though and if someone isn't comfortable with bumping their levels up to the high-normal range then I understand. 

 

The anesthetic/phosphotau connection is very interesting as was the role of lithium in attenuating it. The study was actually a very good read. I'm with you though, the dose makes the poison and with CT we are dealing with a significantly smaller dose. 

 

You bring up a great point about hormesis...in fact, that is one of the primary ways that LLLT works. You ultimately end up with a genetic response to a mild stressor and that is why one dose of LLLT can still have effects weeks later. Pretty cool, imo. 

Edited by lostfalco, 10 December 2015 - 06:53 AM.

[Lsdium]

 

Molecular hydrogen increases ghrelin increases growth hormone. I use this (sorry it's so expensive!) http://www.amazon.co.../dp/B00FBSST8G/

 

 

 

 

Lostfalco, may i ask how long you have used the Hydrogen Water Generator, and do you feel any difference using it?

[lostfalco]

Lostfalco, may i ask how long you have used the Hydrogen Water Generator, and do you feel any difference using it?

 

Hey Lsdium, I bought the generator in late Sept, early Oct of 2014...so a year and a few months. I do notice a small difference on its own which becomes more noticeable in combination with other things. It's a very difficult thing for me to fully recommend at this point (given the price and the small (very possibly placebo) effect) but I think the H2 science is worth keeping an eye on going forward.  

[Kalliste]

Been using 750w halogen lights. No water or color filter though. Just a fan to cool things down and UVEX glasses to protect my eyes. It lifted my winter depression after 15 minutes of light applied to my head in a single session. It also has profound ability to damp my chronic hurting neck. I was partly inspired from this thread since this summer, glad to have found this.

[lostfalco]

Been using 750w halogen lights. No water or color filter though. Just a fan to cool things down and UVEX glasses to protect my eyes. It lifted my winter depression after 15 minutes of light applied to my head in a single session. It also has profound ability to damp my chronic hurting neck. I was partly inspired from this thread since this summer, glad to have found this.

That's awesome, Cosmicalstorm. Light can be a very powerful thing. Thanks for reporting back! 

 

How close did you place your head to the halogen lights? Did you irradiate your entire head, just certain parts?

[lostfalco]

A nice recent article on the cognitive benefits of concentrated oxygen...one of my favorite noots. The study is focused on developmentally disabled individuals but it gives a good summary and links to results in healthy subjects that you can check out if you are so inclined. I think it's fairly safe if you keep your doses reasonably low. 

 

http://www.ncbi.nlm....les/PMC4337321/

 

"The administration of high-concentration oxygen increases memory capability of healthy young and elderly individuals [8-12]. As well, exposure to highly concentrated oxygen positively affects n-back tasks, visuospatial perception, use of verbs, and efficiency in addition performance of healthy young adults [13-19]. Recently, external oxygen administration has been shown to have positive effects on visual matching task performance of intellectually and developmentally disabled individuals [20].

The administration of high-concentration oxygen also leads to cognitive enhancement, as revealed by increases in accuracy [8,10,11,13-18] and/or decreases in response time [8-12,14,16,19,20] during cognitive tasks. Physiological responses such as increased blood oxygen saturation (SpO2) as well as decreased heart rate (HR) have supported the contribution of high-concentration oxygen administration to cognitive performance [8-12,14,16-20].

Many studies with a variety of cognitive tasks were performed using various verification methods to clarify how the administration of high-concentration oxygen enhances cognitive capability of normal people [8-19]."

 

J Physiol Anthropol. 2015 Feb 20;34:3. doi: 10.1186/s40101-015-0043-9.

Effects of 92% oxygen administration on cognitive performance and physiological changes of intellectually and developmentally disabled people.

Kim HS, Choi MH, Baek JH, Park SJ, Lee JC, Jeong UH, Kim SP, Kim HJ, Choi Y, Lim DW, Chung SC.

Abstract

BACKGROUND: 

The present study addressed how 92% oxygen administration affects cognitive performance, blood oxygen saturation (SpO2), and heart rate (HR) of intellectually and developmentally disabled people.

METHODS: 

Seven males (28.9 ± 1.8 years) and seven females (34.4 ± 8.3 years) with intellectual and developmental disabilities (disabled level 2.1 ± 0.5) completed an experiment consisting a 0-back task with normal air (21% oxygen) administered in one run and hyperoxic air (92% oxygen) administered in the other run. The experimental sequence in each run consisted of a 1-min adaptation phase, 2-min control phase, and 2-min 0-back task phase, where SpO2 and HR were gauged for each phase.

RESULTS: 

The administration of 92% oxygen increased 0-back task performance of intellectually and developmentally disabled people, in association with increased SpO2 and decreased HR. Our results demonstrate that sufficient oxygen supply subserving cognitive functions, even as a short-term effect, could increase cognitive ability for the intellectually and developmentally disabled people.

CONCLUSIONS: 

It is concluded that enriched oxygen can positively affect, at least in the short-term, the working memory of those with intellectual and developmental disability.

 

Edited by lostfalco, 10 December 2015 - 05:57 PM.

[BieraK]

I'm really interested by oxygen therapy, is a bit expensive the machine I'm saving money for that.

Have you conducted more experiments with oxygen Lostfalco? 

 

That study shows a short-term effect with oxygen... But as I understand you can extend the effects with a vassodilator or not? If I remember well the effects that you experienced with oxygen concretrator+vibration plate (microvessels vassodilation) was for many hours in the day.

On the otherhand Methylene blue can enhance the effects for a longer time.


I've felt the power of oxygen by methylene blue, the chemical alone enhances oxygen consumption by cells, Oxygen feels great I love that sensation, great clarity and energy, mood is also enhanced by that, breathe is easier and effortless you can feel more oxygen passing.

A combination of Methylene blue+Oxygen Therapy could be really powerful for cognitive function and health... What I still wonder about the possible side effects of MB+Oxygen concentrator? 

Edited by BieraK, 11 December 2015 - 05:29 AM.

[Kalliste]

 

Been using 750w halogen lights. No water or color filter though. Just a fan to cool things down and UVEX glasses to protect my eyes. It lifted my winter depression after 15 minutes of light applied to my head in a single session. It also has profound ability to damp my chronic hurting neck. I was partly inspired from this thread since this summer, glad to have found this.

That's awesome, Cosmicalstorm. Light can be a very powerful thing. Thanks for reporting back! 

 

How close did you place your head to the halogen lights? Did you irradiate your entire head, just certain parts?

 

 

I put the lights extremly close and direct a fan to avoid issues of over-heating. Reading about light treatments I've been getting the impression that very high lux is necessary to combat SAD. Typically I will put the two smaller 150w lights against my ears and the bigger 500w unit leaning towards the back of my head from above (it can be bent 180 degrees so it can be made to "look down on the floor" from a chair.)

Here is a pic of my crude setup, I move it around depending on what body part I want to light up. Also unscrew the cover glass to get some UV though I don't do that a lot because of uncertainty about the danger. Should be good for my winter D-vitamin status.

Attached Files

•  lamp.jpg   62.53KB   4 downloads

Edited by Cosmicalstorm, 11 December 2015 - 05:59 AM.

[lostfalco]

Have you conducted more experiments with oxygen Lostfalco? 

 

That study shows a short-term effect with oxygen... But as I understand you can extend the effects with a vassodilator or not? If I remember well the effects that you experienced with oxygen concretrator+vibration plate (microvessels vassodilation) was for many hours in the day.
 

Hey BieraK, I just set my concentrator back up again today. I'll start testing it out again tomorrow. 

 

The science does indicate short bursts (minutes) of oxygen followed by short term (minutes) learning and memory enhancement. I usually keep my concentrator running and take 'sips' of oxygen ever so often. I have a pulse oximeter that I use to make sure my blood oxygen level is enhanced.  

 

I have combined it with a vibration plate (for microcirculation enhancement) and noticed hours of enhanced energy. There is no science on this that I am aware of. Just an anecdote from my experimentation. 

[lostfalco]

 

I put the lights extremly close and direct a fan to avoid issues of over-heating. Reading about light treatments I've been getting the impression that very high lux is necessary to combat SAD. Typically I will put the two smaller 150w lights against my ears and the bigger 500w unit leaning towards the back of my head from above (it can be bent 180 degrees so it can be made to "look down on the floor" from a chair.)

Here is a pic of my crude setup, I move it around depending on what body part I want to light up. Also unscrew the cover glass to get some UV though I don't do that a lot because of uncertainty about the danger. Should be good for my winter D-vitamin status.

 

Thanks for the report and pic Cosmicalstorm! That's cool it's working so well for you. Have you also tried 460 to 500nm bright light therapy for SAD?

[mettmett]

 

Hey guys,

 

I just finished part I of my II part series on mitochondria.

 

You might find it interesting:  http://remedyrising....tochondria-atp/

What's up mettmett? Nice article man. I'm a big fan of mitochondria myself. =)

 

Yeah, MK-677 is very interesting. Not only does it maintain the pulsatile GH but it also doesn't raise cortisol. Regarding learning and memory, growth hormone causes instant working memory improvements in young and old rodents through enhanced NMDA and AMPA activity. http://www.ncbi.nlm....pubmed/23590874   Could mix very well with an ampakine (obligatory excitotoxicity warning). 

 

Not much, just doing a lot of work!  I thought you might appreciate that article, you are the one who got me interested in mitochondria afterall :P

 

 

 

Also, anyone who wants to improve ghrelin the "natural way," could considering drinking Oolong Tea.

Very interesting. Will have to look into this. Thanks, mettmett. 

 

 

Yeah it's always cool to see that plant substances can interact with the human body.

And since we're on the subject of risky research chemicals I might as well post on SR9009 and SR9011. Pharmacological modulation of clock genes is just so damn cool and sleep, the suprachiasmatic nucleus, circadian biology, etc. are essential to learning and memory. 

 

Ceretropic sells this as well. http://www.ceretropi...-9009-solution/

I've had good results over the years with 465nm light on my intrinsically photosensitive retinal ganglion cells. This the device I have. I use it in the morning and if I need to pull an all-nighter I use it at night. http://www.amazon.co.../dp/B000W8Y7FY/

I am aware of those compounds but I haven't done much research on them yet myself.  I am a fan of bright light, and in my office I currently sit under ~22,000 lumens in the 6500k temperature range.  It feels natural and uplifting.

[mettmett]

 

 

 

 

I see your point about the modest effects of MK-677 as opposed to a pituitary tumor resulting in pathologically high IGF1. My point was really that IGF1 appears to be almost totally nefarious in adults who value longevity. In particular, I'm referring to this epidemiological observation. So really this was more of a general comment on why I think we want to avoid all but absolutely necessary levels of IGF1 in mature adults.

 

 

The sentence in bold is key here and I agree with you.  But isn't having the absolute necessary levels of anything ideal?  Example: exercise, sun light, vitamins, sleep, hormones, etc, etc, etc.  There are many theories on how cancer starts, but if we really knew the main cause then it wouldn't be an issue.  I THINK IGF is bad for cancer because it is growth promoting.  But what if we kept the cancer from ever being formed in the first place?  Then the IGF wouldn't be able to promote the cancerous growth because the cancer cell never existed.  Growth does not equal cancer.  But cancer plus growth factors does mean faster cancer growth.  So essentially I agree with you.

 

A nice recent article on the cognitive benefits of concentrated oxygen...one of my favorite noots. The study is focused on developmentally disabled individuals but it gives a good summary and links to results in healthy subjects that you can check out if you are so inclined. I think it's fairly safe if you keep your doses reasonably low. 

 

http://www.ncbi.nlm....les/PMC4337321/

I am very interested in an oxygen concentration device...especially after reading  a book where they used hyperbaric oxygen therapy + injectable glutiathone.  One day...

 

I'm really interested by oxygen therapy, is a bit expensive the machine I'm saving money for that...

A combination of Methylene blue+Oxygen Therapy could be really powerful for cognitive function and health... What I still wonder about the possible side effects of MB+Oxygen concentrator? 

Me too.  Side effects?  Oxygen Toxicity.  But if my memory serves me correctly, Meth Blue has antioxidant capabilites?  So maybe there is synergy there?  But as always, I think it is another case of the dose makes the poison.  Same deal with IGF... So who's going to be the first to test this out...falco?

Edited by mettmett, 11 December 2015 - 01:47 PM.

[lostfalco]

Since I've been focusing on hormones and their role in learning and memory lately....

 

http://www.ncbi.nlm....pubmed/20018181

 

Brain Res. 2010 Feb 8;1313:9-24. doi: 10.1016/j.brainres.2009.12.010. Epub 2009 Dec 16.

Administration of thyroid hormone increases reelin and brain-derived neurotrophic factor expression in rat hippocampus in vivo.

Sui L1, Ren WW, Li BM.

Author information

Abstract

Thyroid hormones play important roles in the maturation and function of the central nervous system. However, the underlying mechanism behind thyroid hormone-regulated gene expression in the adult brain is not well understood. Two genes critical for neuronal plasticity and implicated in psychiatric disorders, reelin and brain-derived neurotrophic factor (BDNF), were investigated in the present study. Triiodothyronine (T3), the active form of thyroid hormone was administered to young adult rats in two different manners: systemic injection or local brain infusion. Real time RT-PCR results revealed that T3 administration lead to a significant increase in reelin, total BDNF and exon-specific BDNF mRNA expression in the hippocampus. Furthermore, the association of transcriptional coactivators (including steroid receptor coactivator-1 (SRC-1), cAMP response element binding protein-binding protein (CBP), and thyroid hormone receptor associated protein 220 (TRAP 220)) and RNA polymerase II (RNA Pol II), with reelin and BDNF genes in the rat hippocampus displayed a distinct process following thyroid hormone administration. These findings suggest that association of transcriptional coactivators and RNA Pol II with gene promoters may be a possible mechanism explaining T3-induced reelin and BDNF expression in the hippocampus of young adult rats.

 

 

http://www.ncbi.nlm....les/PMC4146262/

 

Neural Regen Res. 2014 Apr 15;9(8):864-71. doi: 10.4103/1673-5374.131602.

The synthetic thyroid hormone, levothyroxine, protects cholinergic neurons in the hippocampus of naturally aged mice.

Fu A1, Zhou R1, Xu X1.

Author information

Abstract

The thyroid hormones, triiodothyronine and thyroxine, play important roles in cognitive function during the mammalian lifespan. However, thyroidhormones have not yet been used as a therapeutic agent for normal age-related cognitive deficits. In this study, CD-1 mice (aged 24 months) were intraperitoneally injected with levothyroxine (L-T4; 1.6 μg/kg per day) for 3 consecutive months. Our findings revealed a significant improvement in hippocampal cytoskeletal rearrangement of actin and an increase in serum hormone levels of L-T4-treated aged mice. Furthermore, the survival rate of these mice was dramatically increased from 60% to 93.3%. The Morris water maze task indicated that L-T4 restored impaired spatial memory in aged mice. Furthermore, level of choline acetyltransferase, acetylcholine, and superoxide dismutase were increased in these mice, thus suggesting that a possible mechanism by which L-T4 reversed cognitive impairment was caused by increased activity of these markers. Overall, supplement of low-dosage L-T4 may be a potential therapeutic strategy for normal age-related cognitive deficits.

 

Edited by lostfalco, 11 December 2015 - 03:27 PM.

[BieraK]

 

Have you conducted more experiments with oxygen Lostfalco? 

 

That study shows a short-term effect with oxygen... But as I understand you can extend the effects with a vassodilator or not? If I remember well the effects that you experienced with oxygen concretrator+vibration plate (microvessels vassodilation) was for many hours in the day.
 

Hey BieraK, I just set my concentrator back up again today. I'll start testing it out again tomorrow. 

 

The science does indicate short bursts (minutes) of oxygen followed by short term (minutes) learning and memory enhancement. I usually keep my concentrator running and take 'sips' of oxygen ever so often. I have a pulse oximeter that I use to make sure my blood oxygen level is enhanced.  

 

I have combined it with a vibration plate (for microcirculation enhancement) and noticed hours of enhanced energy. There is no science on this that I am aware of. Just an anecdote from my experimentation. 

 

 

That is what most intrigues me. It is likely to be able to extend the effects of oxygen supplementation with vascular supplements, Niacin/B3 for example.
 

 

 

 

I'm really interested by oxygen therapy, is a bit expensive the machine I'm saving money for that...

A combination of Methylene blue+Oxygen Therapy could be really powerful for cognitive function and health... What I still wonder about the possible side effects of MB+Oxygen concentrator? 

Me too.  Side effects?  Oxygen Toxicity.  But if my memory serves me correctly, Meth Blue has antioxidant capabilites?  So maybe there is synergy there?  But as always, I think it is another case of the dose makes the poison.  Same deal with IGF... So who's going to be the first to test this out...falco?

 

According to wikipedia article oxygen toxicity is a concern with hyperbaric oxygen therapy also, so Hyperbaric oxygen chamber+methylene blue does not sound like a good idea?.
You have the reason the dose makes the poison here... but this makes think in Myo-inositol tryspyrophosphate:
http://www.longecity...-supply-to-tis/
http://www.longecity...ve-enhancement/

That drug can enhance oxygenation by enhancing hemoglobin...I will search about hemoglobin and methylene in the afternoon.

A small dose of methylene blue like 10 mg could be a good starting point, This really intrigues me.... Why not to try first with bottled oxygen like this? http://mlc-s1-p.mlst...49_032015-F.jpg

[mettmett]

According to wikipedia article oxygen toxicity is a concern with hyperbaric oxygen therapy also, so Hyperbaric oxygen chamber+methylene blue does not sound like a good idea?.

You have the reason the dose makes the poison here...

 

In the book I read they used injectable glutathione which is a strong antioxidant.  In theory this should counter the possible oxygen damage that could occur from excessive oxygen treatment.

So to be clear, with my current knowledge I think that methylene blue + oxygen is a good idea.

But as always proceed with caution and start with a low dose of each.  

 

The only reason I posted that link to oxygen toxicity is because you asked for a possible side effect.  I don't think you will actually reach that toxic level as long as you stay within therapeutic doses.
 

 

but this makes think in Myo-inositol tryspyrophosphate:
http://www.longecity...-supply-to-tis/
http://www.longecity...ve-enhancement/

 

I'll have to check that out!

 

A small dose of methylene blue like 10 mg could be a good starting point, This really intrigues me.... Why not to try first with bottled oxygen like this? http://mlc-s1-p.mlst...49_032015-F.jpg

 

 

 

I haven't done much research on bottled oxygen water but I feel like you would run into similar problems with it as you do with Hydrogen infused water.  I think earlier in this thread someone, maybe falco, discovered that only certain metals can retain Hydrogen in liquid. So by the time the drink made it out of the factory and into your hands, there is likely to be little left. I could be wrong though.  

 

If they do work, these drinks would definitely be a more convenient way to give oxygen a test drive..but the machine would save you money in the long run.

 

Edited by mettmett, 11 December 2015 - 09:58 PM.

[lostfalco]

Light and food are massively important regulators of circadian rhythms and coordinate all of our body's systems so that they work seamlessly together (in large part through clock gene expression). Since we've been talking about 465 to 500nm light and ghrelin lately I figured this study might be of interest. Check it out if you have the time!

 

http://www.ncbi.nlm....les/PMC3796263/

 

Front Neurosci. 2013 Oct 14;7:185. doi: 10.3389/fnins.2013.00185.

Circadian adaptations to meal timing: neuroendocrine mechanisms.

Patton DF1, Mistlberger RE.

Author information

Abstract

Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is directly entrained by daily light-dark (LD) cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs) that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this system.

 

Edited by lostfalco, 12 December 2015 - 01:51 AM.

[lostfalco]

Not necessarily recommending taking it...but melanotan II is an agonist of the melanocortin-4 receptor (and other melanocortin receptors).

 

http://www.jneurosci...t/33/2/464.long

 

J Neurosci. 2013 Jan 9;33(2):464-72. doi: 10.1523/JNEUROSCI.3282-12.2013.

Melanocortin-4 receptor regulates hippocampal synaptic plasticity through a protein kinase A-dependent mechanism.

Shen Y1, Fu WY, Cheng EY, Fu AK, Ip NY.

Author information

• 1Division of Life Science, Molecular Neuroscience Center and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Abstract

Learning and memory require orchestrated regulation of both structural and functional synaptic plasticity in the hippocampus. While a neuropeptide alpha-melanocyte-stimulating hormone, α-MSH, has been implicated in memory acquisition and retention, the functional role of its cognate receptor, melanocortin-4 receptor (MC4R), in hippocampal-dependent synaptic plasticity has not been explored. In this study, we report that activation of MC4R enhances synaptic plasticity through the regulation of dendritic spine morphology and abundance of AMPA receptors. We show that activation of postsynaptic MC4R increases the number of mature dendritic spines and enhances surface expression of AMPA receptor subunit GluA1, resulting in synaptic accumulation of GluA1-containing AMPA receptors. Moreover, MC4R stimulates surface GluA1 trafficking through phosphorylation of GluA1 at Ser845 in a Gα(s)-cAMP/PKA-dependent manner. Blockade of protein kinase A (PKA) signaling abolishes the MC4R-mediated enhancement of neurotransmission and hippocampal long-term potentiation. Importantly, in vivo application of MC4R agonists increases LTP in the mouse hippocampal CA1 region. These findings reveal that MC4R in the hippocampus plays a critical role in the regulation of structural and functional plasticity.

 

 

http://www.ncbi.nlm....pubmed/26003413

 

Mol Cell Neurosci. 2015 Jul;67:13-21. doi: 10.1016/j.mcn.2015.05.004. Epub 2015 May 21.

NDP-α-MSH induces intense neurogenesis and cognitive recovery in Alzheimer transgenic mice through activation of melanocortin MC4 receptors.

Giuliani D1, Neri L2, Canalini F2, Calevro A2, Ottani A2, Vandini E2, Sena P3, Zaffe D3, Guarini S4.

Author information

Abstract

Melanocortins exert neuroprotection in a variety of experimental neurodegenerative disorders, including Alzheimer's disease (AD). Further, in previous research we showed that these endogenous peptides stimulate neurogenesis in an acute neurodegenerative disorder such as ischemic stroke. In the present research, we investigated the potential neurogenic effect of melanocortins in AD using APPSwe transgenic mice (Tg2576). To this purpose, 24week-old animals were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells on days 1-11 of the study. Treatment of Tg2576 mice with nanomolar doses of the melanocortin analog [Nle(4),D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH), administered once daily from day 1 to 50, improved brain histology and cognitive functions relative to saline-treated Tg2576 animals. No signs of toxicity were observed. Immunohistochemical examination of the hippocampus at the end of the study (day 50) showed that NDP-α-MSH-treated Tg2576 mice had a greater number of BrdU immunoreactive cells colocalized with NeuN (an indicator of mature neurons) and Zif268 (an indicator of functionally integrated neurons) in the dentate gyrus, relative to saline-treated Tg2576 animals; no newly formed astrocytes were found. Animal pretreatment with the selective melanocortin MC4 receptor antagonist HS024 before each NDP-α-MSH administration prevented all the beneficial effects of the peptide. The present data indicate that MC4 receptor stimulation by a melanocortin prevents cognitive decline in experimental AD, this effect being associated not only with neuroprotection but also with an intense neurogenesis. MC4 receptor agonists could be innovative and safe candidates to counteract AD progression in humans.

 

Edited by lostfalco, 12 December 2015 - 02:29 AM.

[resveratrol_guy]

With regards to oxygen, there are clearly different benefits on different time scales. On the longterm scale, the Navy studied hyperbaric oxygen therapy in cognitive remediation and concluded that it was bunk. However, as I explained here, I think their analysis was flawed. What they did appear to demonstrate was that merely mild elevation in the partial pressure of oxygen incident to the alveoli is sufficient to obtain substantially all of the benefits. This makes intuitive sense, as the difference between modestly senescent respiration (say, 95% SpO2) and healthy respiration (99%) is merely a small fractional increment in oxyhemoglobin. This is all to say that 92% oxygen concentration strikes me as overkill and perhaps overtaxing of superoxide dismutase. I wonder if the same longterm cognitive benefits could be obtained by using a CPAP while awake, for example.

@mettmett: I think there are plenty of examples where we want to drive certain endogenous substances to thresholds well beyond what's absolutely necessary for survival, for example, vitamin D. With repect to IGF1, the epidemiology suggests to me that we want to drive it far below normal levels. Granted, I agree that growth does not equal cancer. The problem is, there is no current test for one's proximity to cancer. (The theoretical lysis scanner device is IMO the best current proposal for this.) But for now, I suppose the best we can do is to police growth promotion by following an otherwise strict anticancer regimen. Believe me, I'm quite emphathetic to those of us who, like me, are willing to take some risks in order to accelerate neuron growth, for example.
 

@lostfalco: Thanks for drawing attention to MC4, which is amazing news to me. Unfortunately, Melanotan 2 looks like it's suffering from a spate of product fraud. Here's hoping we can find a clean source...

 

[BieraK]

 

According to wikipedia article oxygen toxicity is a concern with hyperbaric oxygen therapy also, so Hyperbaric oxygen chamber+methylene blue does not sound like a good idea?.

You have the reason the dose makes the poison here...

 

In the book I read they used injectable glutathione which is a strong antioxidant.  In theory this should counter the possible oxygen damage that could occur from excessive oxygen treatment.

So to be clear, with my current knowledge I think that methylene blue + oxygen is a good idea.

But as always proceed with caution and start with a low dose of each.  

 

The only reason I posted that link to oxygen toxicity is because you asked for a possible side effect.  I don't think you will actually reach that toxic level as long as you stay within therapeutic doses.
 

 

but this makes think in Myo-inositol tryspyrophosphate:
http://www.longecity...-supply-to-tis/
http://www.longecity...ve-enhancement/

 

I'll have to check that out!

 

A small dose of methylene blue like 10 mg could be a good starting point, This really intrigues me.... Why not to try first with bottled oxygen like this? http://mlc-s1-p.mlst...49_032015-F.jpg

 

 

 

I haven't done much research on bottled oxygen water but I feel like you would run into similar problems with it as you do with Hydrogen infused water.  I think earlier in this thread someone, maybe falco, discovered that only certain metals can retain Hydrogen in liquid. So by the time the drink made it out of the factory and into your hands, there is likely to be little left. I could be wrong though.  

 

If they do work, these drinks would definitely be a more convenient way to give oxygen a test drive..but the machine would save you money in the long run.

 

That bottled is Oxygen for breathing, not oxygenated water... is 99% oxygen in a bottle, so apparently is similar in the effects to the oxygen concentrator. Here cost around 20 dollars.

Well perhaps 30 mg of methylene blue is better? hahhaa.... Methylene blue has antioxidant properties per se, and NAC looks like a good idea, I was thinking in the same thing. C60 Could be another good choice, just for stay in the safe zone.

This makes me think in interesting protocols for health, for example 2 or 3 day fasting with methylene blue+oxygen+c60. Hyperbaric Oxygen Chamber is used with Ketone Bodies for starving cells that rely on glycolysis (Search for Dr D'agostino studies on pubmed).
Methylene blue enhances oxygen consumption, and has interesting properties like Sirt1 activation, AMPK activation, Nrf2 genes upregulation. Fasting with that thing in the body+oxygen could be an excellent approach for mitohormesis, mitophagy, stem cell proliferation and autophagy.

ITPP looks good but has a high price, and I don't know if has some of the methylene blue properties
Just look at this: http://www.ncbi.nlm....pubmed/26603930
 

Edited by BieraK, 12 December 2015 - 03:49 AM.

[mettmett]

Falco, you forgot to include that MT-II can make you tan as fuck.

Bierak, Yeah I am loving methylene blue. I dose between 20-80mg. It's some good stuff.

I'm glad I bought a lot of the powdered variety from bluebrainboost before they went out of business.

I've been reading about ITPP and it seems promising.

[lostfalco]

Check out this vision of beauty...

 

http://www.nature.co...ll/nrn3657.html

 

http://www.ncbi.nlm....pubmed/24588018

 

Nat Rev Neurosci. 2014 Feb;15(2):98-110.

Synaptic changes induced by melanocortin signalling.

Caruso V, Lagerström MC, Olszewski PK, Fredriksson R, Schiöth HB.

Abstract

The melanocortin system has a well-established role in the regulation of energy homeostasis, but there is growing evidence of its involvement in memory, nociception, mood disorders and addiction. In this Review, we focus on the role of the melanocortin 4 receptor and provide an integrative view of the molecular mechanisms that lead to melanocortin-induced changes in synaptic plasticity within these diverse physiological systems. We also highlight the importance of melanocortin peptides and receptors in chronic pain syndromes, memory impairments, depression and drug abuse, and the possibility of targeting them for therapeutic purposes.

 

 

 

 

 

"Short-term plasticity (STP) involves phases of facilitation, depression, augmentation and potentiation, and it strengthens or weakens synaptic transmission. During synaptic facilitation, the arrival of two or more presynaptic action potentials (red dashed lines) leads to the opening of voltage-gated Ca²⁺ channels (VGCCs) for 1 to 10 milliseconds, which enhances synaptic strength, whereas the phase of depression lowers Ca²⁺ entry, causing the opposite effect. An increase in the level of intracellular Ca²⁺ enables synaptic vesicles to fuse with the plasma membrane over a different timescale during augmentation (1 to 10 seconds) or potentiation (10 seconds to minutes). Then, glutamate is released into the synaptic cleft and binds to NMDA receptors (NMDARs) and AMPA receptors (AMPARs). Under these conditions, the pore of the NMDAR is blocked by Mg²⁺ and no current can flow through the channel until prolonged and simultaneous depolarization of the postsynaptic neurons occurs. After the expulsion of Mg²⁺ from the NMDAR channel, Ca²⁺ entry into the pore of the channel promotes long-term plasticity, which results in long-lasting changes such as gene expression and protein synthesis. During long-term potentiation (LTP), cytoskeletal proteins are synthesized and promote the formation of new dendritic spines or the enlargement of pre-existing dendritic spines^201, 202. LTP results in the increased expression of AMPARs, which in turn enhances the strength of the glutamatergic synapse during LTP. Conversely, during long-term depression, dendritic arborization is reduced and is accompanied by decreased surface expression of AMPARs (not shown)^40, 203. Activation of melanocortin 4 receptor (MC4R) enhances LTP through cyclic AMP–protein kinase A (PKA) activity along the Schaffer collaterals, which are axons of pyramidal cells in the CA3 and CA1 region of hippocampus. Once Mg²⁺ is expelled from the NMDAR channel, entry of Ca²⁺into the pore of the channel stimulates production of the second messenger cAMP, which releases the catalytic subunit regulatory site of PKA. PKA induces the association of repressor/activator protein 1 homologue (RAP1; also known as TERF2IP), which in turn activates BRAF-induced phosphorylation of mitogen-activated protein kinase (MAPK) kinase (MEK), which then activates MAPK. MAPK activates transcriptional factor cAMP-responsive element-binding protein (CREB) and the transcription of plasticity-associated genes^59, 75, 76. During the late phase of LTP (L-LTP), the secretory brain-derived neurotrophic factor (BDNF) is synthesized. Other mediators such as Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and PKC promote MAPK phosphorylation via RAS signalling during Ca²⁺ influx; however, the cascade is blocked by PKA and SYNGAP activation²⁰⁴. Postsynaptic Ca²⁺ influx can also induce CREB phosphorylation via CaMKIV and MAPK²⁰⁵. Activation of MC4R enhances cAMP–PKA signalling, which leads to the phosphorylation of the GluA1 subunit of the AMPAR at Ser845. Activation of the MC4R promotes surface expression of AMPARs and maturation of immature dendritic spines, which in turn potentiates L-LTP. As a result, surface trafficking of AMPARs increases and so does the postsynaptic response to glutamate released from the presynaptic terminal. Glutamate released into the synaptic cleft is removed via glial cell-facilitated uptake or enzymatic degradation (not shown). RASGRF, Ras-specific guanine nucleotide-releasing factor 2."

Edited by lostfalco, 15 December 2015 - 05:10 AM.

[lostfalco]

Me too.  Side effects?  Oxygen Toxicity.  But if my memory serves me correctly, Meth Blue has antioxidant capabilites?  So maybe there is synergy there?  But as always, I think it is another case of the dose makes the poison.  Same deal with IGF... So who's going to be the first to test this out...falco?

haha So much pressure. =) We'll see. I'm currently pretty obsessed with peptides and hormones...I kinda feel like I'm raiding a bodybuilder's medicine cabinet. ha I do have some oxygen experiments coming up so I'll let you know when I get to them. 

[lostfalco]

 

You have the reason the dose makes the poison here... but this makes think in Myo-inositol tryspyrophosphate:
http://www.longecity...-supply-to-tis/
http://www.longecity...ve-enhancement/

That drug can enhance oxygenation by enhancing hemoglobin...I will search about hemoglobin and methylene in the afternoon.
 

Thanks for drawing my attention to myo-inositol trypyrophosphate, BieraK! I was vaguely familiar with it but you inspired me to look deeper into the research. That is one badass mechanism of action...allosteric modulation of red blood cells causing enhanced oxygen delivery to cells (it does not increase red blood cell mass like EPO). The exercise gains in rodents are pretty astonishing. This might have some serious nootropic potential. I obviously have some concerns...but I couldn't resist and ordered a gram from Nyles7. http://www.ebay.ph/i...nmUPuGk28FY3h2Q

 

 

http://www.ncbi.nlm....les/PMC2644140/

 

Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1926-9. doi: 10.1073/pnas.0812381106. Epub 2009 Feb 9.

Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin, myo-inositol trispyrophosphate.

Biolo A1, Greferath R, Siwik DA, Qin F, Valsky E, Fylaktakidou KC, Pothukanuri S, Duarte CD, Schwarz RP, Lehn JM, Nicolau C, Colucci WS.

Author information

Abstract

A major determinant of maximal exercise capacity is the delivery of oxygen to exercising muscles. myo-Inositol trispyrophosphate (ITPP) is a recently identified membrane-permeant molecule that causes allosteric regulation of Hb oxygen binding affinity. In normal mice, i.p. administration of ITPP (0.5-3 g/kg) caused a dose-related increase in the oxygen tension at which Hb is 50% saturated (p50), with a maximal increase of 31%. In parallel experiments, ITPP caused a dose-related increase in maximal exercise capacity, with a maximal increase of 57 +/- 13% (P = 0.002). In transgenic mice with severe heart failure caused by cardiac-specific overexpression of G alpha q, i.p. ITPP increased exercise capacity, with a maximal increase of 63 +/- 7% (P = 0.005). Oral administration of ITPP in drinking water increased Hb p50 and maximal exercise capacity (+34 +/- 10%; P < 0.002) in normal and failing mice. Consistent with increased tissue oxygen availability, ITPP decreased hypoxia inducible factor-1alpha mRNA expression in myocardium. It had no effect on myocardial contractility in isolated mouse cardiac myocytes and did not affect arterial blood pressure in vivo in mice. Thus, ITPP decreases the oxygen binding affinity of Hb, increases tissue oxygen delivery, and increases maximal exercise capacity in normal mice and mice with severe heart failure. ITPP is thus an attractive candidate for the therapy of patients with reduced exercise capacity caused by heart failure.

 

Edited by lostfalco, 15 December 2015 - 08:44 PM.

[lostfalco]

@lostfalco: Thanks for drawing attention to MC4, which is amazing news to me. Unfortunately, Melanotan 2 looks like it's suffering from a spate of product fraud. Here's hoping we can find a clean source...

No problem, resveratrol_guy. MC4 increases neurogenesis, reduces inflammation, increases BDNF, etc. Pretty crazy. 

 

I have this to try out. http://www.antiaging...om/256-msh2-pro

 

I heard Ceretropic was making a melanotan 2 nasal spray. I'll send an email over to /u/misteryouaresodumb on reddit and see if that's still in the works. 

Edited by lostfalco, 15 December 2015 - 08:48 PM.

[mettmett]

haha So much pressure. =) We'll see. I'm currently pretty obsessed with peptides and hormones...I kinda feel like I'm raiding a bodybuilder's medicine cabinet. ha I do have some oxygen experiments coming up so I'll let you know when I get to them. 

 

yes hormones are pretty awesome.  testosterone is probably the greatest nootropic...from what i've heard

 

(ITPP)This might have some serious nootropic potential. I obviously have some concerns...but I couldn't resist and ordered a gram from Nyles7. http://www.ebay.ph/i...nmUPuGk28FY3h2Q

 

I have some on the way as well XD

Relevant Reddit Thread: https://www.reddit.c...find_some_itpp/

 

I heard Ceretropic was making a melanotan 2 nasal spray. I'll send an email over to /u/misteryouaresodumb on reddit and see if that's still in the works. 

 

Ceretropic is still quite busy trying to figure out their payment system.  I know there is a lot of stuff they want to do, but they have a lot going on behind the scenes that's holding them back.  

Nasal sprays aren't hard to make yourself.  Just need a (1) nasal spray bottle (2) insulin needle(for reconstitution) (3) uv-treated deionized water(best) or you can use distilled water with NaCl as a preservative(not as stable)

Edited by mettmett, 15 December 2015 - 09:40 PM.

[lostfalco]

 

I have some on the way as well XD

Relevant Reddit Thread: https://www.reddit.c...find_some_itpp/

 

Nice, mettmett. Let me know how it goes for you. I'm gonna start off trying about 20mg and go from there. I only ordered a gram so 100mg doses won't last me too long...although it does appear to have a pretty long half life. 

Edited by lostfalco, 16 December 2015 - 12:45 AM.

[lostfalco]

The Cholinergic Anti-Inflammatory Pathway

 

The "cholinergic anti-inflammatory pathway" is a master regulator of inflammation and is mediated primarily through alpha7 nicotinic acetylcholine receptors and the vagus nerve. Here's what I'm currently experimenting with (I'm currently looking into cheaper options!). 

 

Galantamine  http://www.powdercit...antamine-powder

MSH   http://www.antiaging...om/256-msh2-pro

Ghrelin   http://www.ceretropi...k-677-solution/

 

 

 

 

 

http://www.ncbi.nlm....les/PMC4533839/

 

Brain Behav Immun. 2009 Jan;23(1):41-5. doi: 10.1016/j.bbi.2008.06.011. Epub 2008 Jun 27.

Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway.

Pavlov VA1, Parrish WR, Rosas-Ballina M, Ochani M, Puerta M, Ochani K, Chavan S, Al-Abed Y, Tracey KJ.

Author information

Abstract

The excessive release of cytokines by the immune system contributes importantly to the pathogenesis of inflammatory diseases. Recent advances in understanding the biology of cytokine toxicity led to the discovery of the "cholinergic anti-inflammatory pathway," defined as neural signals transmitted via the vagus nerve that inhibit cytokine release through a mechanism that requires the alpha7 subunit-containing nicotinic acetylcholine receptor (alpha7nAChR). Vagus nerve regulation of peripheral functions is controlled by brain nuclei and neural networks, but despite considerable importance, little is known about the molecular basis for central regulation of the vagus nerve-based cholinergic anti-inflammatory pathway. Here we report that brain acetylcholinesterase activity controls systemic and organ specific TNF production during endotoxemia. Peripheral administration of the acetylcholinesterase inhibitor galantamine significantly reduced serum TNF levels through vagus nerve signaling, and protected against lethality during murine endotoxemia. Administration of a centrally-acting muscarinic receptor antagonist abolished the suppression of TNF by galantamine, indicating that suppressing acetylcholinesterase activity, coupled with central muscarinic receptors, controls peripheral cytokine responses. Administration of galantamine to alpha7nAChR knockout mice failed to suppress TNF levels, indicating that the alpha7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of galantamine. These findings show that inhibition of brain acetylcholinesterase suppresses systemic inflammation through a central muscarinic receptor-mediated and vagal- and alpha7nAChR-dependent mechanism. Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage.

 

http://www.ncbi.nlm....les/PMC4532414/

 

PLoS One. 2015 Aug 11;10(8):e0134648. doi: 10.1371/journal.pone.0134648. eCollection 2015.

Antidiabetic Effect of Galantamine: Novel Effect for a Known Centrally Acting Drug.

Ali MA1, El-Abhar HS2, Kamel MA3, Attia AS4.

Author information Abstract

The cholinergic anti-inflammatory pathway is one of the putative biochemical pathways that link diabetes with Alzheimer disease. Hence, we aimed to verify the potential antidiabetic effect of galantamine, unveil the possible mechanisms and evaluate its interaction with vildagliptin. The n5-STZ rat model was adopted and the diabetic animals were treated with galantamine and/or vildagliptin for 4 weeks. Galantamine lowered the n5-STZ-induced elevation in body weight, food/water intake, serum levels of glucose, fructosamine, and ALT/AST, as well as AChE in the tested organs. Moreover, it modulated successfully the lipid profile assessed in serum, liver, and muscle, and increased serum insulin level, as well as % β-cell function, in a pattern similar to that of vildagliptin. Additionally, galantamine confirmed its antioxidant (Nrf2, TAC, MDA), anti-inflammatory (NF-κB, TNF-α, visfatin, adiponectin) and anti-apoptotic (caspase-3, cytochrome c) capabilities by altering the n5-STZ effect on all the aforementioned parameters. On the molecular level, galantamine/vildagliptin have improved the insulin (p-insulin receptor, p-Akt, GLUT4/GLUT2) and Wnt/β-catenin (p-GSK-3β, β-catenin) signaling pathways. On almost all parameters, the galantamine effects surpassed that of vildagliptin, while the combination regimen showed the best effects. The present results clearly proved that galantamine modulated glucose/lipid profile possibly through its anti-oxidant, -apoptotic, -inflammatory and -cholinesterase properties. These effects could be attributed partly to the enhancement of insulin and Wnt/β-catenin signaling pathways. Galantamine can be strongly considered as a potential antidiabetic agent and as an add-on therapy with other oral antidiabetics.

 

http://www.ncbi.nlm....pubmed/21222261

 

Adv Exp Med Biol. 2010;681:71-87. doi: 10.1007/978-1-4419-6354-3_6.

Melanocortins and the cholinergic anti-inflammatory pathway.

Giuliani D1, Ottani A, Altavilla D, Bazzani C, Squadrito F, Guarini S.

Author information

Abstract

Experimental evidence indicates that small concentrations of inflammatory molecules produced by damaged tissues activate afferent signals through ascending vagus nerve fibers, that act as the sensory arm of an "inflammatory reflex". The subsequent activation of vagal efferent fibers, which represent the motor arm of the inflammatory reflex, rapidly leads to acetylcholine release in organs of the reticuloendothelial system. Acetylcholine interacts with α7 subunit-containing nicotinic receptors in tissue macrophages and other immune cells and rapidly inhibits the synthesis/release of tumor necrosis factor-α and other inflammatory cytokines. This neural anti-inflammatory response called "cholinergic anti-inflammatory pathway" is fast and integrated through the central nervous system. Preclinical studies are in progress, with the aim to develop therapeutic agents able to activate the cholinergic anti-inflammatory pathway. Melanocortin peptides bearing the adrenocorticotropin/α-melanocyte-stimulating hormone sequences exert a protective and life-saving effect in animals and humans in conditions of circulatory shock. These neuropeptides are likewise protective in other severe hypoxic conditions, such as prolonged respiratory arrest, myocardial ischemia, renal ischemia and ischemic stroke, as well as in experimental heart transplantation. Moreover, experimental evidence indicates that melanocortins reverse circulatory shock, prevent myocardial ischemia/reperfusion damage and exert neuroprotection against ischemic stroke through activation of the cholinergic anti-inflammatory pathway. This action occurs via stimulation of brain melanocortin MC3/MC4 receptors. Investigations that determine the molecular mechanisms of the cholinergic anti-inflammatory pathway activation could help design of superselective activators of this pathway.

 

http://www.ncbi.nlm....pubmed/25870195

 

Hypertension. 2015 Jun;65(6):1238-44. doi: 10.1161/HYPERTENSIONAHA.114.04864. Epub 2015 Apr 13.

Endogenous ghrelin attenuates pressure overload-induced cardiac hypertrophy via a cholinergic anti-inflammatory pathway.

Mao Y1, Tokudome T1, Kishimoto I2, Otani K1, Nishimura H1, Yamaguchi O1, Otsu K1, Miyazato M1, Kangawa K1.

Author information

Abstract

Cardiac hypertrophy, which is commonly caused by hypertension, is a major risk factor for heart failure and sudden death. Endogenous ghrelin has been shown to exert a beneficial effect on cardiac dysfunction and postinfarction remodeling via modulation of the autonomic nervous system. However, ghrelin's ability to attenuate cardiac hypertrophy and its potential mechanism of action are unknown. In this study, cardiac hypertrophy was induced by transverse aortic constriction in ghrelin knockout mice and their wild-type littermates. After 12 weeks, the ghrelin knockout mice showed significantly increased cardiac hypertrophy compared with wild-type mice, as evidenced by their significantly greater heart weight/tibial length ratios (9.2±1.9 versus 7.9±0.8 mg/mm), left ventricular anterior wall thickness (1.3±0.2 versus 1.0±0.2 mm), and posterior wall thickness (1.1±0.3 versus 0.9±0.1 mm). Furthermore, compared with wild-type mice, ghrelin knockout mice showed suppression of the cholinergic anti-inflammatory pathway, as indicated by reduced parasympathetic nerve activity and higher plasma interleukin-1β and interleukin-6 levels. The administration of either nicotine or ghrelin activated the cholinergic anti-inflammatory pathway and attenuated cardiac hypertrophy in ghrelin knockout mice. In conclusion, our results show that endogenous ghrelin plays a crucial role in the progression of pressure overload-induced cardiac hypertrophy via a mechanism that involves the activation of the cholinergic anti-inflammatory pathway.

 

Edited by lostfalco, 16 December 2015 - 05:32 PM.