Topical Nitric Oxide as a First - in - Class, Local Antiandrogen Therapy

Sparky4444

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Is there anything that molecule can't do??? Good find squeeg'!!


There is reason that guy won a Nobel prize for his working in NO...In the meantime, I'll continue to wash down those two huge glasses of beet juice a day...it makes you feel pretty damn good and it gives your face a rosy glow -- must be helping somewhat with your scalp
 

IDW2BB

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http://www.specialchem4cosmetics.com/markets/skin-care/news.aspx?id=9848
Novan's Clinical Trial Demonstrates Effective Anti-acne Property of SB204 by Reducing Sebum

SpecialChem - Jun 4, 2013

DURHAM, N.C. -- Novan Therapeutics has announced results from a recent clinical trial demonstrating that nitric oxide releasing drug candidate SB204 reduces colonization of the acne causing bacteria Propionibacterium acnes (P. acnes) in the skin of healthy volunteers. This study in combination with Novan's earlier findings regarding sebum production, suggests the formulation may be capable of targeting multiple factors in acne.
The Phase 1, thirty-subject study was conducted by Dr. James Leyden (KGL, Inc.). This predictive human model has been used to demonstrate the activity of anti-acne therapies like traditional oral antibiotics and topical antibiotics such as clindamycin. In this study, twice daily administration of the topical product was safe and "the treatment was extremely well tolerated," added Dr. Leyden. Several subjects demonstrated a greater than 90 percent reduction of P. acnes when treated with SB204; no vehicle-treated subjects exhibited such a response. A statistically significant difference (p < 0.05) in P. acnescounts was observed between active and vehicle after two weeks.
Acne is the most common skin disease in the United States, affecting more than 50 million people. Antibiotics have been a mainstay for dermatologists due to the ability to reduce P. acnes colonization in the skin and the documented ability to treat inflammatory lesions in acne patients. However, monotherapy usage of these drugs has slowed due to the onset of antibiotic resistance. Nitric oxide is an antimicrobial with a low propensity for resistance and is part of the human body's natural immune response to bacteria. "These unique properties of nitric oxide, in conjunction with the potential to reduce sebum, provide the basis for our belief that SB204 has the possibility to transform acne care," says Dr. Nathan Stasko, Novan President.
"I have always said the 'Holy Grail' of acne treatments would be a topical that can influence sebum production or the physicochemical properties of sebum. If you can do that, the ability to kill P. acnes is icing on the cake," said Dr. Leyden.
SB204 is currently being examined in a Phase 2 study for the treatment of acne. Results of that study are expected early 2014.

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I guess Bryan was wrong about minoxidil. not having an effect on Androgenetic Alopecia like finasteride. does.:hmmm: Would love to hear his explanation.:dunno:

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Now playing 6 degrees to sb204:http://www.ncbi.nlm.nih.gov/pubmed/?term=ondansetron+wnt
Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-hair transplant reuptake inhibitors (e.g. fluoxetine), 5-hair transplant(1) receptor agonists (e.g. buspirone), 5-hair transplant(2) receptor antagonists (e.g. ritanserin), 5-hair transplant(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies. However, further randomized studies with larger samples are warranted to establish their efficacy and safety profiles in the treatment of alcohol dependence.
wait for it....................................................................................................................................................................................................................http://www.ncbi.nlm.nih.gov/pubmed/23493539
What do the Atkins Diet and the traditional Japanese diet have in common? The Atkins Diet is low in carbohydrate and usually high in fat; the Japanese diet is high in carbohydrate and usually low in fat. Yet both work to promote weight loss. One commonality of both diets is that they both eliminate the monosaccharide fructose. Sucrose (table sugar) and its synthetic sister high fructose corn syrup consist of 2 molecules, glucose and fructose. Glucose is the molecule that when polymerized forms starch, which has a high glycemic index, generates an insulin response, and is not particularly sweet. Fructose is found in fruit, does not generate an insulin response, and is very sweet. Fructose consumption has increased worldwide, paralleling the obesity and chronic metabolic disease pandemic. Sugar (i.e., fructose-containing mixtures) has been vilified by nutritionists for ages as a source of "empty calories," no different from any other empty calorie. However, fructose is unlike glucose. In the hypercaloric glycogen-replete state, intermediary metabolites from fructose metabolism overwhelm hepatic mitochondrial capacity, which promotes de novo lipogenesis and leads to hepatic insulin resistance, which drives chronic metabolic disease. Fructose also promotes reactive oxygen species formation, which leads to cellular dysfunction and aging, and promotes changes in the brain's reward system, which drives excessive consumption. Thus, fructose can exert detrimental health effects beyond its calories and in ways that mimic those of ethanol, its metabolic cousin. Indeed, the only distinction is that because fructose is not metabolized in the central nervous system, it does not exert the acute neuronal depression experienced by those imbibing ethanol. These metabolic and hedonic analogies argue that fructose should be thought of as "alcohol without the buzz."
.......................and there you have it.
 

squeegee

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Is there anything that molecule can't do??? Good find squeeg'!!


There is reason that guy won a Nobel prize for his working in NO...In the meantime, I'll continue to wash down those two huge glasses of beet juice a day...it makes you feel pretty damn good and it gives your face a rosy glow -- must be helping somewhat with your scalp

Happy now? lol you own me a grasshoper on tap at the Druides :beer:

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Sparky4444

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Happy now? lol you own me a grasshoper on tap at the Druides :beer:

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well, I'll be happy when we have something to apply -- then you might get that beer ;-)

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..ummm, now we're blaming fructose??? Let's keep this thread on track...humans evolved on fruits just as much as they did on meat...

...cutting back your fruit intake won't help now, even if it is linked..
 

IDW2BB

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well, I'll be happy when we have something to apply -- then you might get that beer ;-)

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..ummm, now we're blaming fructose??? Let's keep this thread on track...humans evolved on fruits just as much as they did on meat...

...cutting back your fruit intake won't help now, even if it is linked..

well.... that would explain why humans have always been bald/balding even before agriculture. What do macaque eat? Also, fruit + booze + western diet is a WHOLE lot of influence on all those pathways and microRNA mentioned in the prior link. Heck, what if during pregnancy, an expectant mother eats a whole bunch of fruit and pasta? What if her mother before her did that? I'm not say'n....I'm just say'n.:dunno:
 

Sparky4444

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well.... that would explain why humans have always been bald/balding even before agriculture. What do macaque eat? Also, fruit + booze + western diet is a WHOLE lot of influence on all those pathways and microRNA mentioned in the prior link. Heck, what if during pregnancy, an expectant mother eats a whole bunch of fruit and pasta? What if her mother before her did that? I'm not say'n....I'm just say'n.:dunno:

Right...but the point is moot now...this is about counter-acting it

NO gets the blood flowin -- but I think we need something in the blood to fight this...NO won't be enough on its own.
 

Armando Jose

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"I have always said the 'Holy Grail' of acne treatments would be a topical that can influence sebum production or the physicochemical properties of sebum. If you can do that, the ability to kill P. acnes is icing on the cake," said Dr. Leyden.
Dr. Jame J Leyden is a good investigator about acne during decades, from early 70`s. He clearly talks about the “physicochemical properties of sebum” Acne and common hairloss are linked in my idea.
I think that the modification of sebum flux acts as a trigger in common hair loss. Sebum is altered passing the time, it is important that sebaceous gland produce sebum but it is necessary that this sebum can be remove from the scalp and pilosebaceous unit. I have also the idea that sebum not only dischard towards the surface of the scalp, Sebum is not only directed outwards but can travel into the hair follicle. In this narrow zone, sebum meets the stem cells and melanocytes. If can be confirmed this assumption, then we can explain the miniaturization of hair loss before the terminal lost of it, and at the same time it could be explain the specific model of hair loss, because it does not affect the sides of head because this area does not occur alterations in sebum flow, creation and elimination of fat.
 

Sparky4444

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" and at the same time it could be explain the specific model of hair loss, because it does not affect the sides of head because this area does not occur alterations in sebum flow, creation and elimination of fat.

...at that point, we're damn near there....if anyone can explain why the sides don't bald but the top does, then bingo...need more on this angle...
 

IDW2BB

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...at that point, we're damn near there....if anyone can explain why the sides don't bald but the top does, then bingo...need more on this angle...

from Armando's post:" I have also the idea that sebum not only dischard towards the surface of the scalp, Sebum is not only directed outwards but can travel into the hair follicle."
 

resu

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The sides do thin, the areas where the frames of my glasses touch the head are thin in a very obvious vertical line till the back of the ear. I think my hair loss is a mix of male pattern baldness with something else that I haven't found any info since the same happens on my legs, the areas where the socks end are hairless. The only common thing is sebum, I think the glasses touching the head and socks (etc..) compress the sebum into the pores or block it causing inflammation and killing the follicle. Sebum and bacteria/fungus shouldn't be overlooked, not the cause but can cause damage in the male pattern baldness region.

Karl Pilkington has thinning on the sides too, google him up.
 

IDW2BB

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"I have always said the 'Holy Grail' of acne treatments would be a topical that can influence sebum production or the physicochemical properties of sebum. If you can do that, the ability to kill P. acnes is icing on the cake," said Dr. Leyden.
Dr. Jame J Leyden is a good investigator about acne during decades, from early 70`s. He clearly talks about the “physicochemical properties of sebum” Acne and common hairloss are linked in my idea.
I think that the modification of sebum flux acts as a trigger in common hair loss. Sebum is altered passing the time, it is important that sebaceous gland produce sebum but it is necessary that this sebum can be remove from the scalp and pilosebaceous unit. I have also the idea that sebum not only dischard towards the surface of the scalp, Sebum is not only directed outwards but can travel into the hair follicle. In this narrow zone, sebum meets the stem cells and melanocytes. If can be confirmed this assumption, then we can explain the miniaturization of hair loss before the terminal lost of it, and at the same time it could be explain the specific model of hair loss, because it does not affect the sides of head because this area does not occur alterations in sebum flow, creation and elimination of fat.

what are your thoughts on the paper Dr. Kelce presented in squeegee's link? what are your thoughts on sb204 based on your theory?

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Armando Jose

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...at that point, we're damn near there....if anyone can explain why the sides don't bald but the top does, then bingo...need more on this angle...

Yeah, it is right ....
sides don't suffer from excess of sebum..... why? Because all days, these hairs, are in contact with an absorbent surface during some hours. Clear and simple.

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from Armando's post:" I have also the idea that sebum not only dischard towards the surface of the scalp, Sebum is not only directed outwards but can travel into the hair follicle."

this explain, in my opinion, the miniaturization of hairs because there is less stem cells arriving to the dermal papilla

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The sides do thin, the areas where the frames of my glasses touch the head are thin in a very obvious vertical line till the back of the ear. I think my hair loss is a mix of male pattern baldness with something else that I haven't found any info since the same happens on my legs, the areas where the socks end are hairless. The only common thing is sebum, I think the glasses touching the head and socks (etc..) compress the sebum into the pores or block it causing inflammation and killing the follicle. Sebum and bacteria/fungus shouldn't be overlooked, not the cause but can cause damage in the male pattern baldness region.

Karl Pilkington has thinning on the sides too, google him up.

good point

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what are your thoughts on the paper Dr. Kelce presented in squeegee's link? what are your thoughts on sb204 based on your theory?

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It is possibe that Nitric oxide can reduce sebocytes proliferation. lipid synthesis and sebum production.... but the real problem in my opinion is that sebum is not eliminated at the proper time

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By the way, I remember my patent with no success with melatonin
http://www.espatentes.com/pdf/2101660_a1.pdf

It was a disappointment, from the beginning, because they had patents in this time I saw the two patents (Regelson and one from Japan) that appeared at the same time, ..., passing the time it continued
http://www.google.com/patents/US6281241 in this patent cited mine


Anyway I do not get to see in those persons who tested it, the holy grail of new hair was impossible, so I thought it should be more useful to keep the hair and that's when I just started to look for alternative method aforementioned
 

Sparky4444

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there is no doubt about it -- as I have aged, my sides and back have gotten finer, not as thick and dense....but it isn't falling out -- yet! :badmood:
 

squeegee

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Sparky4444

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Nitric Oxide with Cialis?.. I have pure Nitrate in a topical form.. and that stuff is so powerful.. I cannot even tolerate it at small dose..it goes in the bloodstream within 2 minutes.. then look like Dracula for 3 days LOL..

IF it would have worked, it would have been out by now....
 

Mr White

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Nitric Oxide is a cool substance. Isn't this used to treat erectile dysfunction, as well? I believe v**** (and other PDE-5 inhibitors) increase NO levels so that more blood can get into the penis.
 

squeegee

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Bump!

[h=1]Inhibition of cytochromes P450 by nitric oxide and a nitric oxide-releasing agent.[/h]Wink DA, Osawa Y, Darbyshire JF, Jones CR, Eshenaur SC, Nims RW.
[h=3]Source[/h]Chemistry Section, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.

[h=3]Abstract[/h]The effect of nitric oxide (NO) on cytochrome P450-mediated benzyloxyresorufin and ethoxyresorufin O-dealkylase activity of rat hepatic postmitochondrial (S-9) or microsomal subfractions, or purified rat liver CYP2B1, was examined. Two distinct inhibitory phases were observed regardless of whether the NO was added prior to initiation of the reactions with NADPH or during the course of substrate turnover. The first was a reversible inhibition characterized by complete cessation of catalytic activity, the duration of which was NO concentration-dependent with an IC50 in the range of 8-60 microM. This phase was followed by a second, irreversible, inhibitory phase characterized by a varying extent of recovery of activity, with inhibition ranging from < 1 to approximately 100%. The extent of this diminution in substrate conversion rate was also NO concentration-dependent, with an IC50 in the range of 13-72 microM, and could be partially abrogated by the inclusion of bovine serum albumin in the reaction mixture. Lower IC50 values for both inhibitory phases were obtained in the case of benzyloxyresorufin O-dealkylase activity than in the case of ethoxyresorufin O-dealkylase activity, suggesting a differential susceptibility to inhibition by NO for the two O-dealkylase activities. A nitric oxide-releasing compound ([Et2NN(O)NO]Na,DEA/NO) caused qualitatively similar inhibitory effects on benzyloxyresorufin O-dealkylase activity when added prior to the initiation of the reactions with NADPH, or during the course of substrate turnover. Based upon these results, it is possible that NO may play a role in the regulation of P450 activity in vivo.

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At the occipital scalp, androgens enhance inducible nitric oxide synthase (iNOS), which catalyzes production of nitric oxide from L-arginine.[SUP][14][/SUP] The induction of nitric oxide synthase usually occurs in an oxidative environment, where high levels of nitric oxide produced interact with superoxide, leading to peroxynitrite formation and cell toxicity. iNOS has been suggested to play a role in host immunity by participating in anti-microbial and anti-tumor activities as part of the oxidative burst[SUP][29][/SUP] of macrophages.[SUP][30][/SUP] The gene coding for nitric oxide synthase is on human chromosome

http://en.wikipedia.org/wiki/Androgenic_alopecia
 

Armando Jose

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the key question could be, androgens enhance inducible iNOS, only in occipital scalp?
 
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