Hair grow Accelerators..
- Thread starter squeegee
- Start date
squeegee
Banned
- Reaction score
- 132
Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian gland.
Schirra F, Richards SM, Sullivan DA.
Source
Harvard Medical School, Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA.
Abstract
PURPOSE:
We tested our hypothesis that testosterone increases the meibomian gland gene expression of numerous enzymes in the cholesterol biosynthetic pathway.
METHODS:
Meibomian glands were obtained from castrated mice treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR.
RESULTS:
Our research demonstrates that testosterone stimulates a significant increase in the mRNA levels of mevalonate kinase, phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl pyrophosphate isomerase, geranylgeranyl pyrophosphate synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and Delta 7-sterol reductase.
CONCLUSIONS:
Our findings indicate that androgens may promote cholesterol biosynthesis in the meibomian gland.
http://www.freepatentsonline.com/y2008/0176908.html
Method of using squalene monooxygenase inhibitors to treat acne
A method for the treatment of acne comprising the administration, to a patient afflicted therewith, of a effective amount of a squalene monooxygenase inhibitor such as tolnaftate, naftifine, terbinafine, butenafine or ciclopirox. An advantage of the present invention relates to the surprisingly speedy onset of effectiveness in relieving acne symptoms. The compound may be administered orally or topically.
DETAILED DESCRIPTION OF THE INVENTION
The term “squalene monooxygenase inhibitor†or “SMI†used herein to refer to a class of substances from the thiocarbamate, allylamine, benzylamine or hydroxypryridone chemical structural classes.
An exemplary thiocarbamate is tolnaftate and its pharmaceutically acceptable salts, prodrugs and esters such as its hydrochloride and phosphates. Tolnaftate is known by the IUPAC name of O-(2-naphthyl)methyl(3-methylphenyl)thiocarbamate. Tolnaftate is disclosed in U.S. Pat. No. 3,334,126 (Miyazaki) as being useful as a fungicide for fungal infections on the human skin. This patent is incorporated herein by reference.
Exemplary allylamines include terbinafine and naftifine and their pharmaceutically acceptable salts, prodrugs and esters such as their hydrochlorides and phosphates. Terbinafine is known by the IUPAC name N,6,6-trimethyl-N-(naphthalene-1-ylmethyl)hept-2-en-4-yn-1-a mine and is disclosed in U.S. Pat. No. 4,755,534 (Stuetz) as possessing chemotherapeutic activity, specifically as antimycotic agents when administered orally. Naftifine is known by the IUPAC name (E)-N-cinnamyl-N-methyl-1-naphthalenemethylamine and is disclosed in U.S. Pat. No. 4,282,251 (Berney) as possessing chemotherapeutic activity, specifically as antimycotic agents when administered orally. This patent is incorporated herein by reference.
An exemplary benzylamine is butenafine and its pharmaceutically acceptable salts, prodrugs and esters such as hydrochloride and phosphates. Butenafine is known by the IUPAC name N-methyl-1-naphthalen-1-yl-{(4-tert-butylphenyl)methyl}methe namine. Butenafine is disclosed in U.S. Pat. No. 5,021,458 (Maeda et al.) as an antifungal compound in the form of liquid preparations, ointment, cream and the like at a concentration of 0.01 to 5%. This patent is incorporated herein by reference.
An exemplary hydroxypryridone is ciclopirox and its pharmaceutically acceptable salts, esters, prodrugs and olamine derivatives. Ciclopirox is known by the IUPAC name 6-cylcohexyl-1-hydroxy-4-methyl-pyridin-2-one. Ciclopirox is disclosed in U.S. Pat. No. 7,026,337 (Bohn et al.) as a topically applied antimycotic preparation suitable for the treatment of prophylaxis of dermatomycoses. This patent is incorporated herein by reference.
In the treatment of acne, a topical solution containing a squalene monooxygenase inhibitor is applied to an affected area, once or twice daily or as needed. The topical solution may be a gel, spray, lotion, wash, shampoo, liquid, cream or any other suitable medium for topical solutions. The solution has an effective amount of squalene monooxygenase inhibitor. The amount of squalene monooxygenase inhibitor may be 0.01 to 50 wt. percent.
The compound may also be provides in tablet, pill, liquid or other acceptable medium for oral administration. The compound can also be combined with other acne treatments such as benzoyl peroxide, clindamycin, erythromycin, sulfur, sodium sulfacetamide, tretinoin, adapalene. A tablet of 250 milligrams, taken once a day, would be sufficient but the dosage can be tailored for each individual patient. The medication may also be ‘pulse’ dosed, with one tablet a day for a week, then skip three weeks and repeated.
Although the exact mechanism for relief of acne symptoms by squalene monooxygenase inhibitors is unknown, the following mechanism is a theory:
Squalene is a 30-carbon linear isoprenoid compound structurally similar to beta-carotene. It is primarily known for its key role as an intermediate in cholesterol production. Squalene monooxygenase catalyzes the insertion of an oxygen atom across a carbon-carbon double bond to form an epoxide. Squalene is distributed ubiquitously in human tissues with the greatest concentration in the skin, where it has a continual presence of 10 to 15 percent.
Squalene is not very susceptible to peroxidation and thus functions in the skin as a quencher of singlet oxygen, protecting human skin surface from lipid peroxidation due to UV radiation. While vital to cholesterol synthesis, from a dermatological standpoint, oxidized squalene has been described a cytotoxic, irritant and strongly comedogenic. Peroxidated squalene induces the production of inflammatory mediators leading to increased lipoxygenase activity and increased inflammation. Oxidized squalene appears to produce micro-aerophilic conditions in the skin and sets up and ecological niche for anaerobic flora leading to bacterial colonization. Bacterial colonization is a secondary effect of comedogenesis induced by formation of squalene oxides.
Squalene monooxygenase inhibitors block the action of squalene monooxygenase in the skin and thus the production of 2, 3 oxidosqualene is reduced. Since 2, 3 oxidosqualene is pro-inflammatory, inflammation and redness of acne lesions are reduced. Ciclopirox, naftifine and terbinafine have been shown to have greater anti-inflammatory ability than 2.5% hydrocortisone. Due to their similar mechanism of action, it can be assumed that butenafine and tolnaftate would have similar anti-inflammatory action. Although not specifically found in the literature, I believe ciclopirox to be an SMI. The major pathway of action for ciclopirox involves chelation of polyvalent cations such as Fe3+. Inhibition of these cations results in inhibition of metal dependent enzymes such as squalene monooxygenase. Squalene monooxygenase is dependent on NADPH cytochrome P450 reductase to donate an electron to the reaction. Ciclopirox chelates the ferric component of NADPH cytochrome p450 reductase thus inhibiting the electron transfer to squlane monooxygenase. Squalene monooxygenase is thus inhibited from oxidizing squalene to 2, 3 oxidosqualane.
The mechanisms by which squalene monooxygenase inhibitors are effective in treating acne are as follows:
1. SMI compounds prevent the formation of pro-inflammatory 2, 3 oxidosqualene in the skin.
2. SMI compounds increase the level of oxygen quenching, anti-inflammatory squalene in the skin.
3. Increased levels of squalene and decreased levels of oxidosqualene in the skin prevent micro-aerophilic conditions that promote anaerobic bacteria colonization. This colonization would lead to comedogenesis and acne formation.
4. By increasing squalene levels and decreasing oxidosqualene levels, SMI compounds can deter or even prevent future acne lesion formation.
These mechanisms lead to decreased redness and inflammation in existing acne lesions resulting in expedited resolution of acne symptoms. In addition, these mechanisms aid in prevention of future acne lesion formation.
While the invention has been disclosed with reference to preferred embodiments, variations and modifications would be apparent to one of ordinary skill in the art. The invention encompasses such variations and modifications.
Schirra F, Richards SM, Sullivan DA.
Source
Harvard Medical School, Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114, USA.
Abstract
PURPOSE:
We tested our hypothesis that testosterone increases the meibomian gland gene expression of numerous enzymes in the cholesterol biosynthetic pathway.
METHODS:
Meibomian glands were obtained from castrated mice treated with vehicle or testosterone for 2 weeks. Tissues were processed for the analysis of selected mRNAs by real-time PCR.
RESULTS:
Our research demonstrates that testosterone stimulates a significant increase in the mRNA levels of mevalonate kinase, phosphomevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl pyrophosphate isomerase, geranylgeranyl pyrophosphate synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and Delta 7-sterol reductase.
CONCLUSIONS:
Our findings indicate that androgens may promote cholesterol biosynthesis in the meibomian gland.
http://www.freepatentsonline.com/y2008/0176908.html
Method of using squalene monooxygenase inhibitors to treat acne
A method for the treatment of acne comprising the administration, to a patient afflicted therewith, of a effective amount of a squalene monooxygenase inhibitor such as tolnaftate, naftifine, terbinafine, butenafine or ciclopirox. An advantage of the present invention relates to the surprisingly speedy onset of effectiveness in relieving acne symptoms. The compound may be administered orally or topically.
DETAILED DESCRIPTION OF THE INVENTION
The term “squalene monooxygenase inhibitor†or “SMI†used herein to refer to a class of substances from the thiocarbamate, allylamine, benzylamine or hydroxypryridone chemical structural classes.
An exemplary thiocarbamate is tolnaftate and its pharmaceutically acceptable salts, prodrugs and esters such as its hydrochloride and phosphates. Tolnaftate is known by the IUPAC name of O-(2-naphthyl)methyl(3-methylphenyl)thiocarbamate. Tolnaftate is disclosed in U.S. Pat. No. 3,334,126 (Miyazaki) as being useful as a fungicide for fungal infections on the human skin. This patent is incorporated herein by reference.
Exemplary allylamines include terbinafine and naftifine and their pharmaceutically acceptable salts, prodrugs and esters such as their hydrochlorides and phosphates. Terbinafine is known by the IUPAC name N,6,6-trimethyl-N-(naphthalene-1-ylmethyl)hept-2-en-4-yn-1-a mine and is disclosed in U.S. Pat. No. 4,755,534 (Stuetz) as possessing chemotherapeutic activity, specifically as antimycotic agents when administered orally. Naftifine is known by the IUPAC name (E)-N-cinnamyl-N-methyl-1-naphthalenemethylamine and is disclosed in U.S. Pat. No. 4,282,251 (Berney) as possessing chemotherapeutic activity, specifically as antimycotic agents when administered orally. This patent is incorporated herein by reference.
An exemplary benzylamine is butenafine and its pharmaceutically acceptable salts, prodrugs and esters such as hydrochloride and phosphates. Butenafine is known by the IUPAC name N-methyl-1-naphthalen-1-yl-{(4-tert-butylphenyl)methyl}methe namine. Butenafine is disclosed in U.S. Pat. No. 5,021,458 (Maeda et al.) as an antifungal compound in the form of liquid preparations, ointment, cream and the like at a concentration of 0.01 to 5%. This patent is incorporated herein by reference.
An exemplary hydroxypryridone is ciclopirox and its pharmaceutically acceptable salts, esters, prodrugs and olamine derivatives. Ciclopirox is known by the IUPAC name 6-cylcohexyl-1-hydroxy-4-methyl-pyridin-2-one. Ciclopirox is disclosed in U.S. Pat. No. 7,026,337 (Bohn et al.) as a topically applied antimycotic preparation suitable for the treatment of prophylaxis of dermatomycoses. This patent is incorporated herein by reference.
In the treatment of acne, a topical solution containing a squalene monooxygenase inhibitor is applied to an affected area, once or twice daily or as needed. The topical solution may be a gel, spray, lotion, wash, shampoo, liquid, cream or any other suitable medium for topical solutions. The solution has an effective amount of squalene monooxygenase inhibitor. The amount of squalene monooxygenase inhibitor may be 0.01 to 50 wt. percent.
The compound may also be provides in tablet, pill, liquid or other acceptable medium for oral administration. The compound can also be combined with other acne treatments such as benzoyl peroxide, clindamycin, erythromycin, sulfur, sodium sulfacetamide, tretinoin, adapalene. A tablet of 250 milligrams, taken once a day, would be sufficient but the dosage can be tailored for each individual patient. The medication may also be ‘pulse’ dosed, with one tablet a day for a week, then skip three weeks and repeated.
Although the exact mechanism for relief of acne symptoms by squalene monooxygenase inhibitors is unknown, the following mechanism is a theory:
Squalene is a 30-carbon linear isoprenoid compound structurally similar to beta-carotene. It is primarily known for its key role as an intermediate in cholesterol production. Squalene monooxygenase catalyzes the insertion of an oxygen atom across a carbon-carbon double bond to form an epoxide. Squalene is distributed ubiquitously in human tissues with the greatest concentration in the skin, where it has a continual presence of 10 to 15 percent.
Squalene is not very susceptible to peroxidation and thus functions in the skin as a quencher of singlet oxygen, protecting human skin surface from lipid peroxidation due to UV radiation. While vital to cholesterol synthesis, from a dermatological standpoint, oxidized squalene has been described a cytotoxic, irritant and strongly comedogenic. Peroxidated squalene induces the production of inflammatory mediators leading to increased lipoxygenase activity and increased inflammation. Oxidized squalene appears to produce micro-aerophilic conditions in the skin and sets up and ecological niche for anaerobic flora leading to bacterial colonization. Bacterial colonization is a secondary effect of comedogenesis induced by formation of squalene oxides.
Squalene monooxygenase inhibitors block the action of squalene monooxygenase in the skin and thus the production of 2, 3 oxidosqualene is reduced. Since 2, 3 oxidosqualene is pro-inflammatory, inflammation and redness of acne lesions are reduced. Ciclopirox, naftifine and terbinafine have been shown to have greater anti-inflammatory ability than 2.5% hydrocortisone. Due to their similar mechanism of action, it can be assumed that butenafine and tolnaftate would have similar anti-inflammatory action. Although not specifically found in the literature, I believe ciclopirox to be an SMI. The major pathway of action for ciclopirox involves chelation of polyvalent cations such as Fe3+. Inhibition of these cations results in inhibition of metal dependent enzymes such as squalene monooxygenase. Squalene monooxygenase is dependent on NADPH cytochrome P450 reductase to donate an electron to the reaction. Ciclopirox chelates the ferric component of NADPH cytochrome p450 reductase thus inhibiting the electron transfer to squlane monooxygenase. Squalene monooxygenase is thus inhibited from oxidizing squalene to 2, 3 oxidosqualane.
The mechanisms by which squalene monooxygenase inhibitors are effective in treating acne are as follows:
1. SMI compounds prevent the formation of pro-inflammatory 2, 3 oxidosqualene in the skin.
2. SMI compounds increase the level of oxygen quenching, anti-inflammatory squalene in the skin.
3. Increased levels of squalene and decreased levels of oxidosqualene in the skin prevent micro-aerophilic conditions that promote anaerobic bacteria colonization. This colonization would lead to comedogenesis and acne formation.
4. By increasing squalene levels and decreasing oxidosqualene levels, SMI compounds can deter or even prevent future acne lesion formation.
These mechanisms lead to decreased redness and inflammation in existing acne lesions resulting in expedited resolution of acne symptoms. In addition, these mechanisms aid in prevention of future acne lesion formation.
While the invention has been disclosed with reference to preferred embodiments, variations and modifications would be apparent to one of ordinary skill in the art. The invention encompasses such variations and modifications.
squeegee
Banned
- Reaction score
- 132
Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes: a possible role in acne vulgaris.
Ottaviani M, Alestas T, Flori E, Mastrofrancesco A, Zouboulis CC, Picardo M.
Source
San Gallicano Dermatological Institute IRCCS, Rome, Italy.
Abstract
In order to investigate whether products derived from the oxidation of sebum can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with peroxidated squalene. NF-kappaB activation, secretion, and expression of IL-6, as well as peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA and protein levels, were measured at the end of the treatment and after 24 and 48 hours of recovery. Squalene peroxidation products were administered in amounts able to elicit significant hyperproliferation and to induce lipoxygenase (LOX) activity. The results showed an early activation of NF-kappaB followed by an increase in PPARalpha mRNA and protein levels. Moreover, squalene peroxides induced an initial upregulation of IL-6 production and secretion that was counteracted by PPARalpha activation, as suggested by the subsequent decrease of NF-kappaB nuclear translocation and IL-6 levels. Inflammatory processes play an important role in the development of acne vulgaris. In combination with our own previous findings, which indicated an association between LOX stimulation and increased percentage of proinflammatory lipids in acne as well as a correlation between increased cytokine levels in the infundibulum, pilosebaceous duct hyperkeratinization, and augmented sebogenesis, the present data further support the involvement of lipid peroxides, in particular squalene peroxides, in establishing an inflammatory process in acne.
Ottaviani M, Alestas T, Flori E, Mastrofrancesco A, Zouboulis CC, Picardo M.
Source
San Gallicano Dermatological Institute IRCCS, Rome, Italy.
Abstract
In order to investigate whether products derived from the oxidation of sebum can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with peroxidated squalene. NF-kappaB activation, secretion, and expression of IL-6, as well as peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA and protein levels, were measured at the end of the treatment and after 24 and 48 hours of recovery. Squalene peroxidation products were administered in amounts able to elicit significant hyperproliferation and to induce lipoxygenase (LOX) activity. The results showed an early activation of NF-kappaB followed by an increase in PPARalpha mRNA and protein levels. Moreover, squalene peroxides induced an initial upregulation of IL-6 production and secretion that was counteracted by PPARalpha activation, as suggested by the subsequent decrease of NF-kappaB nuclear translocation and IL-6 levels. Inflammatory processes play an important role in the development of acne vulgaris. In combination with our own previous findings, which indicated an association between LOX stimulation and increased percentage of proinflammatory lipids in acne as well as a correlation between increased cytokine levels in the infundibulum, pilosebaceous duct hyperkeratinization, and augmented sebogenesis, the present data further support the involvement of lipid peroxides, in particular squalene peroxides, in establishing an inflammatory process in acne.
Squeegee,
whats the latest? I am beginning to experiment with this, at 2%. Im concerned that the 2% has mineral oil in it and am wondering both what you (and anyone else) uses and what the results are to date.
I also addressed this in the growth stimulant forum
thank you!!
whats the latest? I am beginning to experiment with this, at 2%. Im concerned that the 2% has mineral oil in it and am wondering both what you (and anyone else) uses and what the results are to date.
I also addressed this in the growth stimulant forum
thank you!!
squeegee
Banned
- Reaction score
- 132
2020 said:
Did we mention that we cure hair loss? We are curious, interested in about the subject and like to experiment out of the box ideas.. Anything wrong with this? Stick with minoxidil,Finasteride if you like to have a weak dick and Nizoral. Acquire some knowledge then you can come here and judge.
squeegee
Banned
- Reaction score
- 132
2020 said:
stick with the big three treatments.. you are a f*****g annoying troll.. oh yeah BTW.. look at this thread : viewtopic.php?f=23&t=64750&start=0
If you have nothing to back up your mocking or bitching ***.. just stay a lurker.
squeegee
Banned
- Reaction score
- 132
2020 said:
He used minoxidil with Miconazole Nitrate 4% which I have pretty much the same results with. Minoxidil alone wasn't enough to get that kind of regrowth.
Not mad, just fed up with bozos coming on here with limited knowledge on the subject mocking the people experimenting new ideas in a section of the forum dedicated for it. If you hate or disagree on something just add some content to back it up or don't post at all.
Einstein
Established Member
- Reaction score
- 110
2020 said:
Dude everywhere I read your posts you have troll written all over you. You're a fukcing douchebag, either contribute or shut the fukc up and stop barking at members. Go play a video game on your computer or something or go fukc the leprechaun you have hidden in your closet. Just get lost