384 replies to this topic

[wolfeye]

Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue.


Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro.

PMID: 11145393

[MrHappy]

Hmmm dosage?

[wolfeye]

Hmmm dosage?

Sorry, I don't have access to full study.

[rwac]

You can download it here: http://informahealth...164700317362299

The study is talking about concentrations of 5-30 microM in vitro.

[wolfeye]

Thanx rwac

Pain on injection of propofol: a comparison of methylene blue and lidocaine.


STUDY OBJECTIVE:
To investigate whether methylene blue, given before injection of propofol, was effective in reducing the frequency and severity of pain associated with propofol injection.

DESIGN:
Prospective, randomized, double-blinded clinical study.

SETTING:
Operating room of a university hospital.

PATIENTS:
90 adult, ASA physical status 1 and 2 patients undergoing elective surgery.

INTERVENTIONS:
Patients were randomly allocated to one of three groups of 30 patients each. Group I received 50 mg of methylene blue, Group II received 40 mg of lidocaine, and Group III, the control group, was given normal saline. All drugs were given as a 2.0 mL bolus 45 seconds before propofol administration.

MEASUREMENTS:
Injection pain using vocal responses, facial grimacing, arm withdrawal, tears, and questioning of the patient were noted. A 4-point scale was used for documenting pain.

MAIN RESULTS:
Pain frequency was 90% in the saline group, whereas the frequencies were significantly lower in the lidocaine and methylene blue groups (26.7% and 40%, respectively).

CONCLUSIONS:
Intravenous pretreatment with methylene blue appears to be effective in reducing the pain during propofol injection.

PMID: 21663809

Edited by wolfeye, 17 October 2011 - 04:03 PM.

[thedevinroy]

I took some pretty high doses... they are posted somewhere... I believe 200mg. It was definitely not that great of an experience. However, with 60mg, I felt a pretty good antidepressant effect all day into the next. This is the dose for Alzheimer's and Parkinson's research I believe.

This is a little off-topic, but does Vitamin C or another reducer take away the mutagenic effects? I think that link says it is a possibility, but I wasn't sure if there was more research on it confirming the hypothesis.

[MrHappy]

I vaguely recall vitamin E being a possibility. On my phone so no link at the moment.

[thedevinroy]

I vaguely recall vitamin E being a possibility. On my phone so no link at the moment.

*Patiently awaits.*

[keflex]

Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue.


Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro.

PMID: 11145393

I did a search but no luck so I'm wondering, has anyone with MB experience noticed a reduction in frequency or quality of erections?

Androgenic maintenance of the rat erectile response via a non-nitric-oxide-dependent pathway.
Reilly CM, Lewis RW, Stopper VS, Mills TM.

Source

Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000, USA.

Abstract

Prior studies have demonstrated that the erectile response in the rat penis is androgen dependent and is mediated by nitric oxide (NO), the neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS). The present studies used L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, to determine if androgens also regulate alternative pathways leading to the erectile response but not mediated by NO. Castrated rats that were treated with L-NAME (L-NAME CASTRATE) exhibited little or no increase in intracavernosal pressure in response to stimulation of the major pelvic ganglion. This ganglion controls blood flow into the penis and, when stimulated, normally leads to erection. However, when castrated animals were treated with testosterone along with L-NAME (L-NAME TESTO), the animals responded to the ganglionic stimulation with increased intracavernosal pressure. This finding suggests that there are other androgen-dependent pathways that lead to penile erection but are not mediated by NO. Erection occurred in both L-NAME CASTRATE and L-NAME TESTO rats in response to intracavernosal injection of sodium nitroprusside (an NO donor drug), proving that the NO responsive mechanisms were unaffected by the inhibition of NOS activity. To investigate further the nature of this NO independent pathway, L-NAME CASTRATE and L-NAME TESTO rats were treated with either zaprinast (a specific phosphodiesterase 5 inhibitor), which would block the breakdown of cGMP to 5'GMP, or methylene blue (an inhibitor of guanylate cyclase) to prevent the synthesis of cGMP. Zaprinast treatment led to increased erectile response in L-NAME TESTO rats but not in L-NAME CASTRATE rats, demonstrating that androgen-sensitive alternative pathways increased guanylate cyclase activity. Methylene blue inhibited the erectile response in all treatment groups, showing that cyclic GMP is critical to the NO-independent pathway as well as the NO-dependent pathway. Taken together, these results support the hypothesis that androgens maintain the erectile response by alternate pathways, including one that is independent of NO but involves the synthesis of cyclic GMP. PMID: 9432131 [PubMed - indexed for MEDLINE]

[MrHappy]

Hmm still on my phone.. This may have been it, if not, it's an interesting read, anyway

http://www.google.co...Gia1RAMO1Q_BZjA

[thedevinroy]

Hmm still on my phone.. This may have been it, if not, it's an interesting read, anyway

http://www.google.co...Gia1RAMO1Q_BZjA

Na, that's not it, but pretty sure you are right.

Try this one: http://www.ncbi.nlm....pubmed/10793887 I got to go...

[rwac]

Basically, the normal Electron Transport Chain goes through Complex I, Complex III (CoQ10) and Complex IV (cytochrome C).
At each stage, 1 H+ is transported which results in formation of 1 ATP each and 3ATP overall.

On the other hand Methylene Blue bypasses complexes I & III and directly oxidizes cyt-c to run Complex IV, resulting in production of a single ATP instead of three. This prevents formation of free radicals and is thus mitoprotective.

This is my understanding of the matter. I believe exposure to methylene blue actually reduces concentration of complex iii and increases that of complex iv.

[niner]

This is a little off-topic, but does Vitamin C or another reducer take away the mutagenic effects? I think that link says it is a possibility, but I wasn't sure if there was more research on it confirming the hypothesis.

I don't think the in vitro mutagenic effects are a problem in vivo:

Transfusion. 1995 May;35(5):407-13.
Mammalian genotoxicity assessment of methylene blue in plasma: implications for virus inactivation.
Wagner SJ, Cifone MA, Murli H, Dodd RY, Myhr B.

BACKGROUND:

The risk of adverse consequences of virus-inactivation procedures for plasma and cellular blood components must be less than the risk of transfusion-associated viral disease. Previous studies demonstrated that methylene blue, which is currently used in Europe for virus inactivation in fresh-frozen plasma, can elicit mutations in bacterial test systems. This study investigates the potential for methylene blue genotoxicity in two mammalian test systems.
STUDY DESIGN AND METHODS:

Different concentrations of methylene blue were prepared in plasma (heat-treated at 56 degrees C for 1 hour to reduce cytotoxicity) and used, without illumination, in an in vitro mouse lymphoma cell assay designed to detect forward mutations in the gene encoding thymidine kinase. The assay was performed in the presence or absence of rat liver S9 microsomal fraction. Similarly prepared samples of methylene blue in heat-treated plasma were used in an in vivo mouse micronucleus assay. Each system included a negative vehicle control (heat-treated plasma without methylene blue) and a positive control consisting of a known genotoxic agent.
RESULTS:

Intravenous administration to mice of 62 mg per kg of methylene blue did not increase the frequency of micronuclei in polychromatic red cells harvested from bone marrow. However, methylene blue concentrations of 10 micrograms per mL (with S9 activation) and 30 micrograms per mL (without S9 activation) significantly increased the thymidine kinase mutation frequency of mouse lymphoma cells to approximately 110 x 10(-6), from a spontaneous frequency of 28 x 10(-6).
CONCLUSION:

Methylene blue is mutagenic in cultured mammalian cells. In contrast, results from the mouse micronucleus assay suggest that the genotoxicity is not expressed in vivo. Considerably more investigation will be required to assess the genotoxic potential of intravenously administered methylene blue used in virus-inactivation procedures, because of the likelihood of the formation of methylene blue photoproducts or the impact of metabolic conversion of methylene blue to leukomethylene blue in vivo.
Comment in Transfusion. 1995 May;35(5):367-70.

PMID: 7740612

[thedevinroy]

This is a little off-topic, but does Vitamin C or another reducer take away the mutagenic effects? I think that link says it is a possibility, but I wasn't sure if there was more research on it confirming the hypothesis.

I don't think the in vitro mutagenic effects are a problem in vivo:

http://www.ncbi.nlm....pubmed/18685714

2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered methylene blue trihydrate in a 0.5% aqueous methylcellulose solution by gavage at doses of 0, 2.5, 12.5, or 25 mg/kg, 5 days per week for 2 years. Additional groups of 30 male and 30 female mice were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, or 18 months for hematology. Survival of dosed male and female groups exceeded that of the vehicle controls in a generally dose-related manner. Mean body weights of dosed female mice began to increase after weeks 29, 61, and 85, reaching final values that were 113%, 111%, and 106% of vehicle controls for the 2.5, 12.5, and 25 mg/kg groups, respectively.Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. The incidences of carcinoma and of adenoma or carcinoma (combined) of the small intestine occurred with a positive trend in males. The incidences of malignant lymphoma occurred with a positive trend in females, and the incidence in 25 mg/kg males exceeded the historical control range. The incidences of hematopoietic cell proliferation of the spleen were significantly increased in 12.5 and 25 mg/kg males and in 25 mg/kg females. The incidences of inflammation of the nose were significantly increased in 12.5 and 25 mg/kg females. GENETIC TOXICOLOGY:Methylene blue trihydrate was mutagenic in Salmonella typhimurium strains TA98 and TA100 with and without rat or hamster liver S9 activation enzymes; mutagenicity was also observed in Escherichia coli strain WP2 uvrA/pKM101 with and without rat liver S9. In cytogenetic tests with cultured Chinese hamster ovary cells, methylene blue trihydrate induced sister chromatid exchanges and chromosomal aberrations with and without S9. (ABSTRACT TRUNCATED).

This was an in vivo study done on mice and hamsters with a crystal form of the drug (the tihydrate version I believe is methylene blue with water in crystal structure, though in aqueous, it would disperse to normal ... same thing, basically). No human studies on mutagenic effects have been studied. Also, it seems that the reduced form of Methylene Blue and Vitamin C is the active and non-toxic version. This, to me, just means to never take it without Vitamin C or, as mentioned, Vitamin E, or some other reducing agent.

[thedevinroy]

More on Vitamin E: http://www.ncbi.nlm....pubmed/15580660 (notice how it says it can be a pro-oxidant)
More on Pro-Oxidant Vitamins: http://en.wikipedia....xidant_vitamins (pro-oxidants can be reducing agents)

[niner]

http://www.ncbi.nlm....pubmed/18685714

2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered methylene blue trihydrate in a 0.5% aqueous methylcellulose solution by gavage at doses of 0, 2.5, 12.5, or 25 mg/kg, 5 days per week for 2 years. Additional groups of 30 male and 30 female mice were administered the same doses for up to 18 months and were evaluated at 2 weeks and 3, 12, or 18 months for hematology. Survival of dosed male and female groups exceeded that of the vehicle controls in a generally dose-related manner. Mean body weights of dosed female mice began to increase after weeks 29, 61, and 85, reaching final values that were 113%, 111%, and 106% of vehicle controls for the 2.5, 12.5, and 25 mg/kg groups, respectively.Dosed mice developed methemoglobinemia and a regenerative Heinz body anemia. The incidences of carcinoma and of adenoma or carcinoma (combined) of the small intestine occurred with a positive trend in males. The incidences of malignant lymphoma occurred with a positive trend in females, and the incidence in 25 mg/kg males exceeded the historical control range. The incidences of hematopoietic cell proliferation of the spleen were significantly increased in 12.5 and 25 mg/kg males and in 25 mg/kg females. The incidences of inflammation of the nose were significantly increased in 12.5 and 25 mg/kg females. GENETIC TOXICOLOGY:Methylene blue trihydrate was mutagenic in Salmonella typhimurium strains TA98 and TA100 with and without rat or hamster liver S9 activation enzymes; mutagenicity was also observed in Escherichia coli strain WP2 uvrA/pKM101 with and without rat liver S9. In cytogenetic tests with cultured Chinese hamster ovary cells, methylene blue trihydrate induced sister chromatid exchanges and chromosomal aberrations with and without S9. (ABSTRACT TRUNCATED).

[...] Also, it seems that the reduced form of Methylene Blue and Vitamin C is the active and non-toxic version. This, to me, just means to never take it without Vitamin C or, as mentioned, Vitamin E, or some other reducing agent.

Thanks Devin, that is a really interesting abstract. As typical in a tox study, most of the doses are huge, though 2.5 mg/kg isn't crazy. I wonder what those survival numbers looked like for the various doses? They say "generally dose-related". Could that mean the lower dose was better? The body weight numbers are consistent with the lower doses providing better mitochondrial efficiency. They still see an effect even at the megadose, but the trend is consistent with Atamna's observations of an optimum at 100nM in vitro. If only the 25mg/kg dosed males exceeded the historical control range, then the lower doses can't be that bad. It might even be the case that the trend was due to some amount of suppression of illness at the lower doses. Overall, I don't see anything to worry about here. Quite the opposite, in fact. Any drug will cause problems if you dose it high enough, and even the lowest dose they used is way higher than we're using.

[thedevinroy]

Thanks Devin, that is a really interesting abstract. As typical in a tox study, most of the doses are huge, though 2.5 mg/kg isn't crazy. I wonder what those survival numbers looked like for the various doses? They say "generally dose-related". Could that mean the lower dose was better? The body weight numbers are consistent with the lower doses providing better mitochondrial efficiency. They still see an effect even at the megadose, but the trend is consistent with Atamna's observations of an optimum at 100nM in vitro. If only the 25mg/kg dosed males exceeded the historical control range, then the lower doses can't be that bad. It might even be the case that the trend was due to some amount of suppression of illness at the lower doses. Overall, I don't see anything to worry about here. Quite the opposite, in fact. Any drug will cause problems if you dose it high enough, and even the lowest dose they used is way higher than we're using.

Right. I'm not worried about it either. Especially, when you consider the active, reduced form was not found to be genotoxic. 2.5mg/kg is pretty huge of dose, in my opinion. When allometrically scaled (0.02kg mouse, 70kg human, 0.75 exponent) it ends up being 22.75mg for a human dose equivalent. I feel MAO inhibition from as low as 1mg, so for me, 22.75mg is pretty high.

I really don't think they should be giving Alzheimer's and Parkinson's sufferers 60mg or better of the blue, non-reduced form. That's my personal opinion. I do believe that much to be genotoxic. I love old people, and I'd hate them to go from this world with a thousand different disorders from taking some "miracle" drug.

Don't get me wrong, I like methylene blue, but not while it's still blue.

[MrHappy]

I think they realised it too. All of the pharma versions are now using azure-b or leucu-mb.. 2nd generation versions.

[niner]

Don't get me wrong, I like methylene blue, but not while it's still blue.

How are you doing the reduction? Do you mix the MB with the reducing agent and let it sit, or just pop a vitamin C along with the oxidized MB? It was reported somewhere or other that it took three hours to reduce it with ascorbic acid. My only experiment was to grind up a vitamin C/bioflavonoid tablet (all I had on hand) and mix it with about a milligram of MB. It got a lot lighter, but didn't lose all its color. I let it sit overnight. I drank the reduced solution, but it didn't subjectively feel any different than the oxidized stuff.

I think they realised it too. All of the pharma versions are now using azure-b or leucu-mb.. 2nd generation versions.

That's interesting... This is the first I've heard of that.

[thedevinroy]

I take 500mg of Vitamin C and hope my blood stream is a good stirring stick. I really want to get the powder and throw it into the whole bottle so it doesn't stain when it hits the floor. Scrubbing the counter with Vitamin C tablets and water gets kind of annoying.

[niner]

I take 500mg of Vitamin C and hope my blood stream is a good stirring stick. I really want to get the powder and throw it into the whole bottle so it doesn't stain when it hits the floor. Scrubbing the counter with Vitamin C tablets and water gets kind of annoying.

Well, you probably ought to mix up a bottle of leucoMB; it looks like the kinetics of the redox is too slow for it to happen in the tummy. Kind of surprising, imho. That sort of thing is usually pretty fast. And yeah, the staining thing is kind of annoying. Considering the way it stains everything else, I suspect it stains teeth too.

[rwac]

Well, you probably ought to mix up a bottle of leucoMB; it looks like the kinetics of the redox is too slow for it to happen in the tummy. Kind of surprising, imho.

I believe oxygen from dissolved air is sufficient to oxidize LeucoMB, just shaking a bottle of lmb in water will bring some of the color back. It's not that surprising since MB is used for it's redox properties.

[niner]

I believe oxygen from dissolved air is sufficient to oxidize LeucoMB, just shaking a bottle of lmb in water will bring some of the color back. It's not that surprising since MB is used for it's redox properties.

It's weird that it seems to be asymmetric. It seems like the reduction is harder than the oxidation. Maybe it's just that all it takes is a little bit of the oxidized product to see the blue color, but for it to be completely colorless, you really have to reduce all of it?

[manic_racetam]

It gets pretty close to colorless but always seems to keep a tiny hint of blue. I've tried adding ridiculous amounts of ascorbic acid and leaving it over night but it seems to never fully turn clear.

I have a bottle at work with about 30mgs that I was sipping from for a few days. I added about 3g's of ascorbic acid. It has a tiny tint of blue, but my boss couldn't tell. He asked why I was leaving a half full bottle of water laying around the office.

Still makes your pee blue though.

[rwac]

It's weird that it seems to be asymmetric. It seems like the reduction is harder than the oxidation. Maybe it's just that all it takes is a little bit of the oxidized product to see the blue color, but for it to be completely colorless, you really have to reduce all of it?

MB is a pretty strong dye, so yeah you would have to reduce all of it. Did you try reducing the air in the bottle and sealing it overnight? An airtight container might do the trick ...

[niner]

Still makes your pee blue though.

That means it's getting re-oxidized in the body. Well, it's probably better to ingest it in the reduced form so you don't use up your endogenous antioxidants reducing it.

Did you try reducing the air in the bottle and sealing it overnight? An airtight container might do the trick ...

You know, I think it was open to the air, and now that I think about it, I seem to remember that it was stratified, with more blue on top. I think I'll re-do this...

[wolfeye]

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice

Background and Objective: The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS).
Materials and Methods: Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1 ^st , 3 ^rd , 5 ^th , 7 ^th ). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days.
Results: The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05).
Conclusion: The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.

http://www.ijp-onlin...29;aulast=Kumar

Edited by wolfeye, 20 October 2011 - 02:06 PM.

[wolfeye]

Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.

ETHNOPHARMACOLOGICAL RELEVANCE:
Aloysia gratissima (Gill. et Hook) Tronc. (Verbenaceae) is used traditionally for the treatment of headache, bronchitis, and nervous systems disorders including depression.
AIM OF THE STUDY:

To investigate the antidepressant-like and neuroprotective effects of Aloysia gratissima aqueous extract (AE) and the involvement of l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway.

MATERIALS AND METHODS:
The antidepressant-like effect of AE was evaluated through behavioral despair in forced swimming test (FST) and tail suspension test (TST). Swiss albino mice were treated by oral route and after 1h were analyzed the time of immobility in the FST and TST. In addition, the neuroprotective effect of AE against glutamate excitotoxicity was evaluate through cell viability of hippocampal slices, phosphorylation of Akt, and the immunocontent of inducible oxide nitric synthase (iNOS) were investigated by western blotting.

RESULTS:
The immobility time in the FST and TST were reduced by AE (100-1000 and 10-300 mg/kg, respectively). The antidepressant-like effect of AE in the TST was prevented by the pretreatment with N-methyl-d-aspartate (NMDA), l-arginine or sildenafil. The subeffective dose of AE produced a synergistic antidepressant-like effect with MK-801 (an antagonist of NMDA receptor), methylene blue, l-NNA (an inhibitor of NO synthase) or ODQ (an inhibitor of soluble guanylate cyclase). In ex vivo experiments, pretreatment with AE prevented the loss of cell viability induced by glutamate, thus affording neuroprotection. Glutamate toxicity caused a decreased Akt phosphorylation and an increased iNOS expression.

CONCLUSIONS:
The present study provides convincing evidence of neuroprotection and the involvement of the l-arginine-NO-cGMP pathway in the antidepressant-like effect of AE. Therefore, AE could be of potential interest for the treatment of depressive disorders and neurological conditions associated with glutamate excitotoxicity.

PMID: 21767626

[noos]

In which areas does MB inhibit NO production, because NO is protective for cardiovascular health, it is in certain areas of the brain?

[thedevinroy]

Oh and I didn't (say or) mean that Methylene Blue is de-oxidized in my stomach. I said in my blood stream. I know Methylene Blue is a stubborn son of a gun to get to reduced form... but my blood stream seems to be a pretty darn good stirring stick, mixing it with Vitamin C or whatever.

Edited by devinthayer, 20 October 2011 - 08:55 PM.