Jacob
Senior Member
- Reaction score
- 44
Newly Discovered Factor in Androgenetic Alopecia. The Cure is Near?
- Thread starter yassin
- Start date
can someone give a quick overview of whats going on? Did we figure out right now that COX is the culprit and cause of male pattern baldness? I'm confused...
young trunks
New Member
- Reaction score
- 0
me too...and why does it take half a day or a whole day for people to respond? we should just have a chat room..
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check this out: http://relax-health.blogspot.com/2011/08/block-cyclooxygenase-in-order-to-reduce.html
These drugs work to block cyclooxygenase in order to reduce and prevent inflammation. Ibuprofen, steroids, Aleve, Vioxx, aspirin, and Celebrex are just some of the names used for over-the-counter and prescription medications that are in this class. As these drugs have become more popular with each passing year the side effects have become more apparent. Patients are showing increased risks of heart attacks and strokes, prolonged stomach irritation, ulcers, and lethal gastric hemorrhages. In their practice they have begun to use fish oil and omega-3 essential fatty acids in an attempt to reduce or replace as many manufactured anti-inflammatory medications as possible. In their experience they found enough anecdotal evidence to believe that fish oil is one of the most promising natural anti-inflammatory supplements available today. The real plus to using fish oil is a lack of lethal side effects.
OMEGA 3
Saint-Loup
Member
- Reaction score
- 1
A new involvement of PGD2 and CRTH2 receptor in apoptosis of cells ??
Prostaglandin D(2) induces apoptosis of human osteoclasts by activating the CRTH2 receptor and the intrinsic apoptosis pathway.
Prostaglandin D(2) (PGD(2)) is a lipid mediator synthesized from arachidonic acid that directly activates two specific receptors, the D-type prostanoid (DP) receptor and chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). PGD(2) can affect bone metabolism by influencing both osteoblast and osteoclast (OC) functions, both cells involved in bone remodeling and in in vivo fracture repair as well. The objective of the present study was to determine the effects of PGD(2), acting through its two specific receptors, on human OC apoptosis. Human OCs were differentiated in vitro from peripheral blood mononuclear cells in the presence of receptor activator for nuclear factor κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), and treated with PGD(2), its specific agonists and antagonists. Treatment with PGD(2) for 24hours in the presence of naproxen (10μM) to inhibit endogenous prostaglandin production increased the percentage of apoptotic OCs in a dose-dependent manner, as did the specific CRTH2 agonist compound DK-PGD(2) but not the DP agonist compound BW 245C. In the absence of naproxen, the CRTH2 antagonist compound CAY 10471 reduced OC apoptosis rate but the DP antagonist BW A868C had no effect. The induction of PGD(2)-CRTH2 dependent apoptosis was associated with the activation of caspase-9, but not caspase-8, leading to caspase-3 cleavage. These data show that PGD(2) induces human OC apoptosis through activation of CRTH2 and the apoptosis intrinsic pathway.
http://www.ncbi.nlm.nih.gov/pubmed/22705147
Prostaglandin D(2) induces apoptosis of human osteoclasts by activating the CRTH2 receptor and the intrinsic apoptosis pathway.
Prostaglandin D(2) (PGD(2)) is a lipid mediator synthesized from arachidonic acid that directly activates two specific receptors, the D-type prostanoid (DP) receptor and chemoattractant receptor homologous molecule expressed on T-helper type 2 cells (CRTH2). PGD(2) can affect bone metabolism by influencing both osteoblast and osteoclast (OC) functions, both cells involved in bone remodeling and in in vivo fracture repair as well. The objective of the present study was to determine the effects of PGD(2), acting through its two specific receptors, on human OC apoptosis. Human OCs were differentiated in vitro from peripheral blood mononuclear cells in the presence of receptor activator for nuclear factor κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), and treated with PGD(2), its specific agonists and antagonists. Treatment with PGD(2) for 24hours in the presence of naproxen (10μM) to inhibit endogenous prostaglandin production increased the percentage of apoptotic OCs in a dose-dependent manner, as did the specific CRTH2 agonist compound DK-PGD(2) but not the DP agonist compound BW 245C. In the absence of naproxen, the CRTH2 antagonist compound CAY 10471 reduced OC apoptosis rate but the DP antagonist BW A868C had no effect. The induction of PGD(2)-CRTH2 dependent apoptosis was associated with the activation of caspase-9, but not caspase-8, leading to caspase-3 cleavage. These data show that PGD(2) induces human OC apoptosis through activation of CRTH2 and the apoptosis intrinsic pathway.
http://www.ncbi.nlm.nih.gov/pubmed/22705147
Saint-Loup
Member
- Reaction score
- 1
PGH1, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP2
Prostaglandin H(1) (PGH(1)) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as "anti-inflammatory". Herein we present evidence that PGH(1) is a potent activator of the pro-inflammatory PGD(2) receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca(2+) flux studies reveal that PGH(1) activates CRTH2 as PGH(2), PGD(2) or PGD(1) do. The PGH(1) precursor DGLA and the other PGH(1) metabolites did not display such effect. PGH(1) specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH(1) is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH(1) mediates migration of and Ca(2+) flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH(1) as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase.
http://www.ncbi.nlm.nih.gov/pubmed/22442685
Prostaglandin H(1) (PGH(1)) is the cyclo-oxygenase metabolite of dihomo-γ-linolenic acid (DGLA) and the precursor for the 1-series of prostaglandins which are often viewed as "anti-inflammatory". Herein we present evidence that PGH(1) is a potent activator of the pro-inflammatory PGD(2) receptor CRTH2, an attractive therapeutic target to treat allergic diseases such as asthma and atopic dermatitis. Non-invasive, real time dynamic mass redistribution analysis of living human CRTH2 transfectants and Ca(2+) flux studies reveal that PGH(1) activates CRTH2 as PGH(2), PGD(2) or PGD(1) do. The PGH(1) precursor DGLA and the other PGH(1) metabolites did not display such effect. PGH(1) specifically internalizes CRTH2 in stable CRTH2 transfectants as assessed by antibody feeding assays. Physiological relevance of CRTH2 ligation by PGH(1) is demonstrated in several primary human hematopoietic lineages, which endogenously express CRTH2: PGH(1) mediates migration of and Ca(2+) flux in Th2 lymphocytes, shape change of eosinophils, and their adhesion to human pulmonary microvascular endothelial cells under physiological flow conditions. All these effects are abrogated in the presence of the CRTH2 specific antagonist TM30089. Together, our results identify PGH(1) as an important lipid intermediate and novel CRTH2 agonist which may trigger CRTH2 activation in vivo in the absence of functional prostaglandin D synthase.
http://www.ncbi.nlm.nih.gov/pubmed/22442685
Nice work, The more reason we should USE an CRTH2 ANTAGONIST. for the moment, we have these Options:
OC000459: which still not ready!!..
Ramatroban, Widely available for cheap.
TM30089, Which seems very nice also because its not an TP Antagonist. its more selective then ramatroban.
.
Ive looked the the structures of TM30089 and Ramatroban they are ALmost the same!
Ramatroban: http://www.chemietek.com/products.aspx?pid=133
TM30089: http://www.chemietek.com/products.aspx?pid=134
as you see they are almost identical, and we should try to get TM30089, I havent done reasearch yet, but maybe this cas number is already pre produced and on stock by some chinese labs/traders.
As for Ramatroban. Im Using it now for couple of weeks. I do notice Shedding stop, and My ACNE did 100% disappeared. But I can not really see an positive effect on my hairline at the moment. Im sure I need PGE2 as addon to see some regrowth.
OC000459: which still not ready!!..
Ramatroban, Widely available for cheap.
TM30089, Which seems very nice also because its not an TP Antagonist. its more selective then ramatroban.
.
Ive looked the the structures of TM30089 and Ramatroban they are ALmost the same!
Ramatroban: http://www.chemietek.com/products.aspx?pid=133
TM30089: http://www.chemietek.com/products.aspx?pid=134
as you see they are almost identical, and we should try to get TM30089, I havent done reasearch yet, but maybe this cas number is already pre produced and on stock by some chinese labs/traders.
As for Ramatroban. Im Using it now for couple of weeks. I do notice Shedding stop, and My ACNE did 100% disappeared. But I can not really see an positive effect on my hairline at the moment. Im sure I need PGE2 as addon to see some regrowth.
squeegee
Banned
- Reaction score
- 132
"Our previous studies show that long-term testosterone treatment augments vascular tone under physiological conditions and exacerbates endotoxin-induced inflammation in the cerebral circulation. However, testosterone can be metabolized by aromatase to estrogen, evoking a balance between androgenic and estrogenic effects. Therefore, we investigated the effect of the nonaromatizable androgen receptor agonist, dihydrotestosterone (DHT), on the inflammatory nuclear factor-κB (NFκB) pathway in cerebral blood vessels. Cerebral arteries were isolated from orchiectomized male rats treated chronically with DHT in vivo. Alternatively, pial arteries were isolated from orchiectomized males and were exposed ex vivo to DHT or vehicle in culture medium. DHT treatment, in vivo or ex vivo, increased nuclear NFκB activation in cerebral arteries and increased levels of the proinflammatory products of NFκB activation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Effects of DHT on COX-2 and iNOS were attenuated by flutamide. In isolated pressurized middle cerebral arteries from DHT-treated rats, constrictions to the selective COX-2 inhibitor NS398 or the selective iNOS inhibitor L-nil, [L-N6-(Iminoethyl)lysine], were increased, confirming a functional consequence of DHT exposure. In conclusion, activation of the NFκB-mediated COX-2/iNOS pathway by the selective androgen receptor agonist, DHT, results in a state of vascular inflammation. This effect may contribute to sex-related differences in cerebrovascular pathophysiology."
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Suppression of cyclooxygenase-2 overexpression by 15S-hydroxyeicosatrienoic acid in androgen-dependent prostatic adenocarcinoma cells.
Pham H, Banerjee T, Ziboh VA.
Source
Department of Dermatology, School of Medicine, University of California-Davis, 95616, USA.
Abstract
Emerging reports now implicate alterations of arachidonic acid (AA) metabolism with prostate carcinogenesis. To test this hypothesis, androgen-primed benign hyperplastic (BHC) and malignant tumorigenic (MTC) cells derived from the Lobund-Wistar rat model of autochthonous prostate adenocarcinoma were incubated with (14)C-AA. Our data using MTCs revealed enhanced dual metabolism of (14)C-AA via COX to generate increased PGE(2) and via 5-lipoxygenase (LOX) to generate increased 5S-HETE in tumorigenic cells. Western blot of MTCs revealed upregulation of COX-2 expression. This paralleled the increased biosynthesis of PGE(2). Since some polyunsaturated fatty acids have been reported to modulate AA metabolism and tumorigenesis, we primed the cells with either gamma-linolenic acid (GLA) or its in vivo metabolite, 15S-HETrE, prior to incubation with AA. Our data revealed suppression of COX-2 expression/PGE(2) biosynthesis. In parallel, priming cells with 15S-HETrE resulted in greater suppression of COX-2 expression/PGE(2) biosynthesis. These findings suggest that 15S-HETrE could function in vivo after dietary intake of GLA to suppress DHT-enhanced prostatic COX-2 expression/PGE(2) biosynthesis and, thus, alleviate tumor growth and progression.
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Suppression of cyclooxygenase-2 overexpression by 15S-hydroxyeicosatrienoic acid in androgen-dependent prostatic adenocarcinoma cells.
Pham H, Banerjee T, Ziboh VA.
Source
Department of Dermatology, School of Medicine, University of California-Davis, 95616, USA.
Abstract
Emerging reports now implicate alterations of arachidonic acid (AA) metabolism with prostate carcinogenesis. To test this hypothesis, androgen-primed benign hyperplastic (BHC) and malignant tumorigenic (MTC) cells derived from the Lobund-Wistar rat model of autochthonous prostate adenocarcinoma were incubated with (14)C-AA. Our data using MTCs revealed enhanced dual metabolism of (14)C-AA via COX to generate increased PGE(2) and via 5-lipoxygenase (LOX) to generate increased 5S-HETE in tumorigenic cells. Western blot of MTCs revealed upregulation of COX-2 expression. This paralleled the increased biosynthesis of PGE(2). Since some polyunsaturated fatty acids have been reported to modulate AA metabolism and tumorigenesis, we primed the cells with either gamma-linolenic acid (GLA) or its in vivo metabolite, 15S-HETrE, prior to incubation with AA. Our data revealed suppression of COX-2 expression/PGE(2) biosynthesis. In parallel, priming cells with 15S-HETrE resulted in greater suppression of COX-2 expression/PGE(2) biosynthesis. These findings suggest that 15S-HETrE could function in vivo after dietary intake of GLA to suppress DHT-enhanced prostatic COX-2 expression/PGE(2) biosynthesis and, thus, alleviate tumor growth and progression.
Nice work, The more reason we should USE an CRTH2 ANTAGONIST. for the moment, we have these Options:
OC000459: which still not ready!!..
Ramatroban, Widely available for cheap.
TM30089, Which seems very nice also because its not an TP Antagonist. its more selective then ramatroban.
.
Ive looked the the structures of TM30089 and Ramatroban they are ALmost the same!
Ramatroban: http://www.chemietek.com/products.aspx?pid=133
TM30089: http://www.chemietek.com/products.aspx?pid=134
as you see they are almost identical, and we should try to get TM30089, I havent done reasearch yet, but maybe this cas number is already pre produced and on stock by some chinese labs/traders.
As for Ramatroban. Im Using it now for couple of weeks. I do notice Shedding stop, and My ACNE did 100% disappeared. But I can not really see an positive effect on my hairline at the moment. Im sure I need PGE2 as addon to see some regrowth.
Ramatroban and TM30089 are as effective according to CRTH2 Antagonism., But TM30089 is much more sellective!
http://www.ncbi.nlm.nih.gov/pubmed/17328802
Abstract
BACKGROUND:
Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit asthma-like pathology.
METHODS:
Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histopathology were examined in a mouse asthma model.
RESULTS:
TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia.
CONCLUSION:
This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.
squeegee
Banned
- Reaction score
- 132
Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression.
Müller-Decker K, Leder C, Neumann M, Neufang G, Bayerl C, Schweizer J, Marks F, Fürstenberger G.
Source
Section of Eicosanoids and Epithelial Tumor Development, Deutsches Krebsforschungszentrum, Heidelberg, Germany. K.Mueller-Decker@dkfz.de
Abstract
Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.
Müller-Decker K, Leder C, Neumann M, Neufang G, Bayerl C, Schweizer J, Marks F, Fürstenberger G.
Source
Section of Eicosanoids and Epithelial Tumor Development, Deutsches Krebsforschungszentrum, Heidelberg, Germany. K.Mueller-Decker@dkfz.de
Abstract
Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.
squeegee
Banned
- Reaction score
- 132
Role of COX-1 and COX-2 on skin PGs biosynthesis by mechanical scratching in mice.
Sugimoto M, Arai I, Futaki N, Hashimoto Y, Honma Y, Nakaike S.
Source
Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Kita-ku, Saitama 331-9530, Japan. masanori.sugimoto@po.rd.taisho.co.jp
Abstract
We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.
Sugimoto M, Arai I, Futaki N, Hashimoto Y, Honma Y, Nakaike S.
Source
Department of Pharmacology, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Kita-ku, Saitama 331-9530, Japan. masanori.sugimoto@po.rd.taisho.co.jp
Abstract
We examined the involvement of cyclooxygenase (COX)-1 and COX-2 on mechanical scratching-induced prostaglandins (PGs) production in the skin of mice. The dorsal regions of mice were scratched using a stainless brush. COXs expressions in the skin were analyzed using real-time PCR and Western blotting. The effect of acetylsalicylic acid (ASA) on the ability of PGs production were determined based on skin PGs level induced by arachidonic acid (AA) application. Mechanical scratching increased PGD2, PGE2, PGI2 and PGF(2 alpha). COX-1 was constitutively expressed and COX-2 expression was enhanced by scratching. Intravenous administration of ASA inhibited PGs biosynthesis in the normal skin. PGs levels of the skin 6h after ASA administration (ASA 6 h) were almost equal to those of the skin 10 min after ASA administration (ASA 10 min). In the scratched skin, AA-induced PGE2 and PGI2 of ASA 6 h were significantly higher than those of ASA 10 min. The skin PGD2 and PGF(2 alpha) of ASA 10 min were almost same to those of ASA 6 h. In the normal skin of COX-1-deficient mice, skin PGD2 level was lower than that of wild-type mice, although PGE2, PGI2 and PGF(2 alpha) levels were almost equal to those of wild type. In the scratched skin of COX-1-deficient mice, PGD2, PGE2, PGI2 and PGF(2 alpha) levels were lower than those of wild-type mice. These results suggested that cutaneous PGD2 could be mainly produced by COX-1, and PGE2 and PGI2 could be produced by COX-1 and COX-2, respectively, in mice.
Well, I'm trying my best to Obtain chemicals Like PGE2 at the moment, but its kind of hard to get.
it would go allot faster, If more people would help to get our hands on these chemicals. instead of having the awaiting intill someone else does the work attitude.
it would go allot faster, If more people would help to get our hands on these chemicals. instead of having the awaiting intill someone else does the work attitude.
squeegee
Banned
- Reaction score
- 132
Miconazole inhibition of platelet aggregation by inhibiting cyclooxygenase.
Ishikawa S, Manabe S, Wada O.
Abstract
Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment.
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Effect of minoxidil on platelet function and the synthesis of prostaglandins in platelets.
O'Barr TP, Swanson EW, Fitzpatrick JE, Corby DG.
Source
Department of Clinical Investigation, Fitzsimons Army Medical Center.
Abstract
At the 12.5 micrograms level, minoxidil prevents the irreversible aggregation of platelets by 2 x 10(-6) mol/L adenosine diphosphate (ADP). Levels of minoxidil greater than 12.5 micrograms cause a reversal of primary aggregation by 2 x 10(-6) mol/L ADP. Aggregation of platelets in response to 125 micrograms of arachidonic acid is measurably reduced by 12.5 micrograms of minoxidil and totally suppressed by 30 micrograms. Concurrent with the inhibition of platelet aggregation, increasing concentrations of minoxidil cause a gradual reduction in the synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2). In the presence of 100 micrograms of minoxidil, PGE2 is reduced from a control value of 87.7 +/- 2.2 pg/ml to 23.9 +/- 3.2 pg/ml. At this level of minoxidil, TxB2 drops from 105 +/- 3.3 ng/ml to 10.5 +/- 2.6 ng/ml. The effect of minoxidil on platelet aggregation is not associated with increased cyclic adenosine monophosphate synthesis. All data support the conclusion that minoxidil functions (in platelet metabolism) primarily as a cyclooxygenase inhibitor.
Ishikawa S, Manabe S, Wada O.
Abstract
Platelet dysfunction was found in rabbits to which a dose of miconazole nitrate (1.6 mg/kg body wt) therapeutic for human subjects had been given intravenously. The present experiments were conducted to elucidate the mechanism of inhibitory effects of miconazole on platelet function. After administration of a single dose of miconazole, rabbit platelet aggregation induced by collagen and sodium arachidonate was inhibited significantly for approximately 24 hr. On the other hand, hypertriglycemia, one of the major side effects of this drug, was not seen during 2 days of observations, nor were any other outstanding manifestations observed. In in vitro experiments, miconazole nitrate (10 microM) also significantly inhibited rabbit and human platelet aggregation (P less than 0.01). Biochemical analyses revealed that the stimulant-induced formation of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), metabolites via cyclooxygenase, was inhibited by miconazole nitrate in both human and rabbit platelets in vitro. PGE2 production was decreased dose-dependently with the increase of miconazole concentration (10 to 100 microM), and the decrease was in parallel with a decrease of TXB2 production. In addition, malondialdehyde (MDA) production of human and rabbit platelets induced by exogenous arachidonate and collagen was also inhibited significantly by miconazole. Chromatographic studies showed that the amount of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), a metabolite via lipoxygenase, was increased markedly in accordance with the miconazole-induced decrease of TXB2 and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) formation in both human and rabbit platelets. These results indicate that miconazole nitrate inhibits platelet cyclooxygenase, without affecting the stimulant-induced release of arachidonic acid from platelet phospholipids. Use of this drug in the treatment of systemic fungal infection appears to be increasing. Careful attention should be paid to the inhibitory effects of miconazole on platelet function, especially in the case of intravenous treatment.
- - - Updated - - -
Effect of minoxidil on platelet function and the synthesis of prostaglandins in platelets.
O'Barr TP, Swanson EW, Fitzpatrick JE, Corby DG.
Source
Department of Clinical Investigation, Fitzsimons Army Medical Center.
Abstract
At the 12.5 micrograms level, minoxidil prevents the irreversible aggregation of platelets by 2 x 10(-6) mol/L adenosine diphosphate (ADP). Levels of minoxidil greater than 12.5 micrograms cause a reversal of primary aggregation by 2 x 10(-6) mol/L ADP. Aggregation of platelets in response to 125 micrograms of arachidonic acid is measurably reduced by 12.5 micrograms of minoxidil and totally suppressed by 30 micrograms. Concurrent with the inhibition of platelet aggregation, increasing concentrations of minoxidil cause a gradual reduction in the synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2). In the presence of 100 micrograms of minoxidil, PGE2 is reduced from a control value of 87.7 +/- 2.2 pg/ml to 23.9 +/- 3.2 pg/ml. At this level of minoxidil, TxB2 drops from 105 +/- 3.3 ng/ml to 10.5 +/- 2.6 ng/ml. The effect of minoxidil on platelet aggregation is not associated with increased cyclic adenosine monophosphate synthesis. All data support the conclusion that minoxidil functions (in platelet metabolism) primarily as a cyclooxygenase inhibitor.
squeegee
Banned
- Reaction score
- 132
Combination therapy with rofecoxib and finasteride in the treatment of men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).
Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, Cardi A, Salvatori G, Sciarra A.
Source
Department Urology, University La Sapienza, Urology U Bracci, V. Policlinico, 00161 Rome, Italy.
Abstract
PURPOSE:
Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays either a pro-inflammatory effect or a proliferative effect on prostate cells. The aim of this study is to analyze whether combination therapy with rofecoxib, a COX-2 inhibitor, and finasteride offers an advantage compared to finasteride monotherapy in patients with BPH.
MATERIALS AND METHODS:
This is a single centre unblinded trial. Forty-six consecutive men with LUTS and BPH were entered into the study and were randomized to receive rofecoxib 25mg/day plus finasteride 5mg/day (group B) versus finasteride 5mg/day alone (group A) for 24 weeks. Inclusion criteria included also a prostate size greater than 40 cc. The efficacy and safety of treatments were assessed at baseline and at week 4, 12 and 24.
RESULTS:
In our population, both treatments (groups A and B) produced statistically significant improvements in total IPSS and Q(max) from baseline during follow-up, although they were very low in particular for the finasteride alone group at 4 weeks. We found that finasteride monotherapy produces very little improvement at the 1 month interval. In comparing group A with group B, a significantly higher improvement in IPSS (p=0.0001) and Q(max) (p=0.03) was obtained in group B at 4 weeks interval (% cases with IPSS reduction >4 points: group B=34.7, group A=0; % cases with Q(max) improvement >3 ml/s: group B=8.7, group A=0), whereas at week 24, the differences between the two treatments were not significant (p>0.05).
CONCLUSIONS:
In our population, the advantage of the combination therapy compared to finasteride alone is significant in a short-term interval (4 weeks). It can be hypothesized that the association of rofecoxib with finasteride induces a more rapid improvement in clinical results until the effect of finasteride becomes predominant.
Di Silverio F, Bosman C, Salvatori M, Albanesi L, Proietti Pannunzi L, Ciccariello M, Cardi A, Salvatori G, Sciarra A.
Source
Department Urology, University La Sapienza, Urology U Bracci, V. Policlinico, 00161 Rome, Italy.
Abstract
PURPOSE:
Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays either a pro-inflammatory effect or a proliferative effect on prostate cells. The aim of this study is to analyze whether combination therapy with rofecoxib, a COX-2 inhibitor, and finasteride offers an advantage compared to finasteride monotherapy in patients with BPH.
MATERIALS AND METHODS:
This is a single centre unblinded trial. Forty-six consecutive men with LUTS and BPH were entered into the study and were randomized to receive rofecoxib 25mg/day plus finasteride 5mg/day (group B) versus finasteride 5mg/day alone (group A) for 24 weeks. Inclusion criteria included also a prostate size greater than 40 cc. The efficacy and safety of treatments were assessed at baseline and at week 4, 12 and 24.
RESULTS:
In our population, both treatments (groups A and B) produced statistically significant improvements in total IPSS and Q(max) from baseline during follow-up, although they were very low in particular for the finasteride alone group at 4 weeks. We found that finasteride monotherapy produces very little improvement at the 1 month interval. In comparing group A with group B, a significantly higher improvement in IPSS (p=0.0001) and Q(max) (p=0.03) was obtained in group B at 4 weeks interval (% cases with IPSS reduction >4 points: group B=34.7, group A=0; % cases with Q(max) improvement >3 ml/s: group B=8.7, group A=0), whereas at week 24, the differences between the two treatments were not significant (p>0.05).
CONCLUSIONS:
In our population, the advantage of the combination therapy compared to finasteride alone is significant in a short-term interval (4 weeks). It can be hypothesized that the association of rofecoxib with finasteride induces a more rapid improvement in clinical results until the effect of finasteride becomes predominant.
zombiehair
Member
- Reaction score
- 3
here is an interesting write up. Lots of stuff here we have at home now we can try.backed up by links to studys.
this bloke has also been on the search. http://www.bodyhealth-mindhealth.com/2012/03/hair-loss-prevention.html
Hair Loss Prevention?
Could tea, ginger or aspirin reduce or prevent hair loss? If some recent findings about male pattern baldness are true they just might be able to. But I'm not talking about eating or drinking them. They would need to be applied to the scalp. This might seem like the strange things people have done over the years to regrow hair, such as putting cow pats on their heads or rubbing in strange concoctions, but there is science behind it.
A team of researchers at the University of Pennsylvania say that an enzyme called prostaglandin D2 synthase (PTGDS) and its product, a protein called prostaglandin D2 (PDG2), is three times more prevalent in the bald scalp areas of men with male pattern baldness than in the areas with hair (1). It is thought that PDG2 interferes with the growth of hair follicle stem cells in their scalps.
Bald areas of scalp still have the hair follicle stem cells but they don't develop into mature hair follicles capable of growing normal hair.
The research team believe that if PGD2's effects could be blocked it might allow the stem cells to do their job of creating mature hair follicles. There are various types of prostaglandins and they have many effects throughout the body. Some, including PGD2, are involved in inflammatory responses. To have an effect they must bind to a receptor on their target cells. PGD2 binds to a receptor on hair follicles called GPR44, also called CRTH2 (yes, I know, very boring names). If the receptor could be blocked, PDG2 wouldn't be able to act and this should result in normal hair growth. If this idea is correct, it might stop further hair loss and it might lead to growth on the bald patches. Or it might stop further loss but have no effect on the bald patches. There are experimental compounds in development now which are designed to block PGD2 from binding to GPR44. These are new drugs that can only be made in a laboratory and that will make a lot of money for the companies that produce them. And cost a lot of money to buy. The good news is that there might be a way to save money and make your own treatments.
As far as I know, there aren't any natural substances in everyday use that have the ability to bind with GPR44 but there definitely are others that can inhibit the production of PGD2. I will deal with the latter, the inhibitors of PGD2, in this article. These substances that can inhibit PGD2 are found in the foodstuffs I mentioned above.
An enzyme called cyclo-oxegenase-2 (COX-2) converts the omega-6 fatty acid, arachidonic acid (AA) to PGD2. If that conversion can be stopped or reduced anywhere along the chain it will stop or reduce the effects of PGD2 on the hair follicles. Constituents of the foodstuffs I mentioned can stop or reduce how much AA is converted to PGD2 or they can reduce the effectiveness or production of COX-2.
The active ingredients in those foodstuffs that could inhibit the production of this prostaglandin are quercetin in tea and various compounds in ginger.
I mentioned aspirin too but this is the drug form of salicylic acid. Salicylic acid is found in many plants (and we also manufacture it in our bodies). Salicylic acid, the stuff found in plants, can be toxic if too much is absorbed through the skin. And, as the form used to test inhibition of COX in vitro is aspirin or sodium salicylate, I'm not sure if salicylic acid from plants such as meadowsweet or willow bark would be safe or even if it would work.
You might be tempted to dissolve an aspirin tablet in water and then apply that to your skin but you'll also be rubbing in all the fillers and caking agents that are used to make tablets. Aspirin toxicity could also be a problem. And some people would get skin reactions. I think it would be better to use tea or ginger. But ginger can also cause skin rashes in some people. If you decide to use these substances you should test some on a small area of skin first where a rash won't be noticeable, such as an arm. No doubt, there will even be some people who would develop a rash after applying tea to their skin, so you must decide if the potential risks are worth it.
I found lots of studies which showed the required effects of quercetin, aspirin and ginger on COX-2 and PDG2. But then I realised that I couldn't use those studies. I forgot about metabolism. In all those studies the foods were fed to the participants. They had the required effects on COX-2 and PGD2 but, as they had gone through the digestive system, their actions could have been due to the changes they underwent during digestion. I needed to find if these substances would have similar effects on isolated cells because, when they are rubbed on the scalp, they will come into direct contact with the skin and follicle cells. They won't be changed by metabolism as they would be if they were eaten as foods. Luckily, there are studies which show that they do affect cells directly and inhibit or reduce the actions of PGD2 or COX-2. This is one case where I will use the results of in vitro studies where cells in a dish are treated with some substance to see what happens. I would usually ignore such studies because I normally deal with substances that are eaten or drunk and so are subjected to all the processes of metabolism.
I have spent more than a week researching this and I want to get on with it so I'll quickly list the studies which I want to use as evidence. They are not about reducing or stopping hair loss. As far as I know there aren't any that examine the properties of these foodstuffs for that purpose. These studies are mainly about cancer and arthritis because of the role played in those diseases by COX-2 and inflammation. They found that the substances under discussion here inhibited COX-2 or the production of PGD2 and they were done with isolated cells - which is what I was looking for.
Quercetin was found to inhibit the enzymatic activity of COX-2(2) and to reduce its production (3).
Ginger inhibited both COX-2 (4) and PGD2 (5).
Aspirin can inhibit the activity or suppress the production of COX-2 (6) (7) (8). But, at least in cultures of smooth muscle cells or endothelial cells (reference 8), its inhibition of COX-2 is transient, and prostaglandin production begins again within 2-5 hours. It may have a longer effect on the cells in the scalp but I can't be sure. There is also the question of aspirin toxicity. For these reasons I think aspirin should be the last of these substances anyone should put their faith in. If you do decide to try it, buy the soluble kind of tablets as they dissolve very easily.
As I said above, none of these studies looked at hair follicles or the skin cells in the scalp and I can't guarantee that the same effects will be found in them but these substances do have affects on PGD2 and COX-2 so could have the same effects in the scalp.
Quercetin
Quercetin is a flavonoid found in many plants and foods. Tea contains very high amounts compared with other foods (9). Green and black tea leaves when dry contain a mean average of between 204 and 264 mg/100g. Decaffeinated tea contains more than ordinary. But Oolong contains hardly any - less than 2mg/100g. Use as little water as possible when infusing the tea or other substances. When tea is brewed normally, with lots of water, 100g only contains about 2mg of quercetin. Naturally, most of the cup of tea is water. So just use enough water to cover the leaves and mash them and squeeze them to get as much out as possible and then you'll approach the 200-odd mg/100g found in dry tea leaves. This will make a stronger, more concentrated, infusion so that you will only need to use perhaps a teaspoonful on your scalp - depending on the size of the bald patch.
There is some confusion about how soluble quercetin is in water. This is because it comes in 2 forms: quercetin aglycone and quercetin glycoside. 'Aglycone' means 'without sugar' and 'glycoside' means 'with sugar'. It's a bit more complicated than that but, not being a biochemist and not wanting to bore you more than I usually do, we'll just leave it at that. Most of the quercetin in foods is the glycoside form but some parts of some foods contain more of the aglycone form. The flesh of onions and shallots, like other food sources, contain mostly the glycoside form (about 90%) but their skins contain about 80% aglycone. It is only the aglycone form that is not soluble in water (although it is a bit more soluble in hot water). The glycoside form is soluble in water and that is the predominant form in tea.
Ginger
Ginger should be cut into small pieces and heated in water. Again, use as little water as possible to obtain a strong infusion.
Ginger contains many constituents. The main one, gingerol, is transformed into shogaols when it is dried or cooked. The study referred to as number 4 used a methanol (alcohol) extract of ginger. This contained various gingerols, shogaols, gingerdiones and other constituents of ginger. One form of gingerol and two of shogaols inhibited COX-2. Luckily, both water and alcohol can be used to extract the constituents of ginger so you can use water to avoid any potential problems of applying alcohol to your skin.
I must point out that a patent was applied for a number of years ago to use a special preparation of ginger extracts as a hair growth inhibitor but this was for body hair. I'm not sure if it was ever put into production nor how successful it would be as a body hair inhibitor. Body hair and scalp hair are affected by different things and, even if it was successful in its intended use, I don't think it would have an inhibitory effect on scalp hair. But that is only my opinion and is not based on any evidence.
Another thing to be aware of is that COX-2 is also involved in the production of another prostaglandin called PGE2, and this is necessary for skin health. Something that interferes with the production or activity of COX-2 might also interfere with PGE2. So, you would have to weigh up the chances of reduced skin health in your pursuit of more hair. Although if you manage to grow some hair it will cover up any dry or flaky skin that might be caused by lack of PGE2.
Many substances have a low permeability through the skin and they need something to help them penetrate deeply enough to have an effect on the skin cells. It's mainly the outer layer of skin, the stratum corneum, that is the barrier. Some oils can provide that permeability to get through the stratum corneum. So can ethanol (alcohol) but I don't think it's a good idea to put alcohol on the skin. It is an irritant for some people and possibly carcinogenic. A study into ways of making formulations more easily absorbed by human skin found that a mixture of 10% jojoba oil and 30% corn germ oil gave the best penetration of the vegetable oils tested.(10). This was made into an emulsion with water. Emulsions are a combination of two liquids that normally wouldn't be able to mix but do so with the addition of an emulsifier. .
I think an emulsion would be the best way of delivering one of our substances to the scalp cells. Make an infusion with hot water and then add an emulsifier such as lecithin and then add a mixture of 25% jojoba oil and 75% corn germ oil. There should be about half water and half oil.
Tocopherols also inhibited COX-2, as was found in the study in reference 3, above. Both alpha- and gamma- tocopherol showed this ability. They are two of the forms of vitamin E. In the study of skin penetration enhancers, olive oil performed the worst. It is one of the main sources of alpha-tocopherol. Corn germ oil is one of the main sources of gamma-tocopherol and, as it shows such good penetration power, is the one to use.
Lecithin, mentioned above, usually comes in granules but liquid lecithin is also available. If you use the granules make sure they dissolve properly in the water.
Making the hair loss prevention lotion
Distilled water would be better than tap water but if you use water from the tap it would be better to filter it. Make the infusion of your choice - tea or ginger - and make it strong with very little water. When you've done that and you've mashed and strained out the tea leaves or ginger pieces, add the lecithin and stir it until it dissolves. Then add the oil a little bit at a time and stir until the oil and water have mixed and formed a creamy texture. Only make enough for a few days so the mixture will always be fresh. If using ginger, cut the pieces as small as you can get them so more of the active ingredients will be absorbed by the water.
I'm sorry if the negative possibilities have dampened any initial enthusiasm but any pharmaceutical product they bring out will also have drawbacks and potentially harmful side effects.
Try this at your own risk or, to put it another way (and I couldn't resist saying this), on your own head be it.
Curcumin, a constituent of turmeric, looked very promising when I first started researching this. Like quercetin, ginger and aspirin it inhibited the production of COX-2 and I wrote at length about it. Then further research turned up the fact that it is used to make a paste for the removal of body hair. It is used a lot for this purpose in India. Apparently, it works by weakening the hair roots. So that idea had to be consigned to the scrap heap. Never mind. If there's any merit in this idea of using common household items to stop hair loss there should be enough power in the other three substances to do the job.
References
1. Science Translational Medicine 2012 Mar 21;4(126):126ra34.
Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.
2. Cancer Chemotherapy and Pharmacology. 2006 Dec;58(6):816-25.
Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin.
3. Mutatation Research. 2004 Jul 13;551(1-2):245-54.
Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription.
4. Fitoterapia. 2011 Jan;82(1):38-43.
Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale).
5. Prostaglandins, Leukotrienes and Medicine. 1984 Feb;13(2):227-35.
Effects of aqueous extracts of onion, garlic and ginger on platelet aggregation and metabolism of arachidonic acid in the blood vascular system: in vitro study.
6. Proceedings of the National Academy of Sciences of the U S A. 1991 Mar 15;88(6):2384-7.
Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells.
7. Proceedings of the National Academy of Sciences of the U S A. 1999 Apr 27;96(9):5292-7.
Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate.
8. Proceedings of the National Academy of Sciences of the U S A. 1987 Mar;84(5):1417-20.
Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity.
9. USDA Database for the Flavonoid Content of Selected Foods, March 2003.
10. Journal of Cosmetic Science. 2007 May-Jun;58(3):245-54.
Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.
- - - Updated - - -
Their are a few easy to obtain options above with links to studies etc for anyone wanting to try somthing now.
this bloke has also been on the search. http://www.bodyhealth-mindhealth.com/2012/03/hair-loss-prevention.html
Hair Loss Prevention?
Could tea, ginger or aspirin reduce or prevent hair loss? If some recent findings about male pattern baldness are true they just might be able to. But I'm not talking about eating or drinking them. They would need to be applied to the scalp. This might seem like the strange things people have done over the years to regrow hair, such as putting cow pats on their heads or rubbing in strange concoctions, but there is science behind it.
A team of researchers at the University of Pennsylvania say that an enzyme called prostaglandin D2 synthase (PTGDS) and its product, a protein called prostaglandin D2 (PDG2), is three times more prevalent in the bald scalp areas of men with male pattern baldness than in the areas with hair (1). It is thought that PDG2 interferes with the growth of hair follicle stem cells in their scalps.
Bald areas of scalp still have the hair follicle stem cells but they don't develop into mature hair follicles capable of growing normal hair.
The research team believe that if PGD2's effects could be blocked it might allow the stem cells to do their job of creating mature hair follicles. There are various types of prostaglandins and they have many effects throughout the body. Some, including PGD2, are involved in inflammatory responses. To have an effect they must bind to a receptor on their target cells. PGD2 binds to a receptor on hair follicles called GPR44, also called CRTH2 (yes, I know, very boring names). If the receptor could be blocked, PDG2 wouldn't be able to act and this should result in normal hair growth. If this idea is correct, it might stop further hair loss and it might lead to growth on the bald patches. Or it might stop further loss but have no effect on the bald patches. There are experimental compounds in development now which are designed to block PGD2 from binding to GPR44. These are new drugs that can only be made in a laboratory and that will make a lot of money for the companies that produce them. And cost a lot of money to buy. The good news is that there might be a way to save money and make your own treatments.
As far as I know, there aren't any natural substances in everyday use that have the ability to bind with GPR44 but there definitely are others that can inhibit the production of PGD2. I will deal with the latter, the inhibitors of PGD2, in this article. These substances that can inhibit PGD2 are found in the foodstuffs I mentioned above.
An enzyme called cyclo-oxegenase-2 (COX-2) converts the omega-6 fatty acid, arachidonic acid (AA) to PGD2. If that conversion can be stopped or reduced anywhere along the chain it will stop or reduce the effects of PGD2 on the hair follicles. Constituents of the foodstuffs I mentioned can stop or reduce how much AA is converted to PGD2 or they can reduce the effectiveness or production of COX-2.
The active ingredients in those foodstuffs that could inhibit the production of this prostaglandin are quercetin in tea and various compounds in ginger.
I mentioned aspirin too but this is the drug form of salicylic acid. Salicylic acid is found in many plants (and we also manufacture it in our bodies). Salicylic acid, the stuff found in plants, can be toxic if too much is absorbed through the skin. And, as the form used to test inhibition of COX in vitro is aspirin or sodium salicylate, I'm not sure if salicylic acid from plants such as meadowsweet or willow bark would be safe or even if it would work.
You might be tempted to dissolve an aspirin tablet in water and then apply that to your skin but you'll also be rubbing in all the fillers and caking agents that are used to make tablets. Aspirin toxicity could also be a problem. And some people would get skin reactions. I think it would be better to use tea or ginger. But ginger can also cause skin rashes in some people. If you decide to use these substances you should test some on a small area of skin first where a rash won't be noticeable, such as an arm. No doubt, there will even be some people who would develop a rash after applying tea to their skin, so you must decide if the potential risks are worth it.
I found lots of studies which showed the required effects of quercetin, aspirin and ginger on COX-2 and PDG2. But then I realised that I couldn't use those studies. I forgot about metabolism. In all those studies the foods were fed to the participants. They had the required effects on COX-2 and PGD2 but, as they had gone through the digestive system, their actions could have been due to the changes they underwent during digestion. I needed to find if these substances would have similar effects on isolated cells because, when they are rubbed on the scalp, they will come into direct contact with the skin and follicle cells. They won't be changed by metabolism as they would be if they were eaten as foods. Luckily, there are studies which show that they do affect cells directly and inhibit or reduce the actions of PGD2 or COX-2. This is one case where I will use the results of in vitro studies where cells in a dish are treated with some substance to see what happens. I would usually ignore such studies because I normally deal with substances that are eaten or drunk and so are subjected to all the processes of metabolism.
I have spent more than a week researching this and I want to get on with it so I'll quickly list the studies which I want to use as evidence. They are not about reducing or stopping hair loss. As far as I know there aren't any that examine the properties of these foodstuffs for that purpose. These studies are mainly about cancer and arthritis because of the role played in those diseases by COX-2 and inflammation. They found that the substances under discussion here inhibited COX-2 or the production of PGD2 and they were done with isolated cells - which is what I was looking for.
Quercetin was found to inhibit the enzymatic activity of COX-2(2) and to reduce its production (3).
Ginger inhibited both COX-2 (4) and PGD2 (5).
Aspirin can inhibit the activity or suppress the production of COX-2 (6) (7) (8). But, at least in cultures of smooth muscle cells or endothelial cells (reference 8), its inhibition of COX-2 is transient, and prostaglandin production begins again within 2-5 hours. It may have a longer effect on the cells in the scalp but I can't be sure. There is also the question of aspirin toxicity. For these reasons I think aspirin should be the last of these substances anyone should put their faith in. If you do decide to try it, buy the soluble kind of tablets as they dissolve very easily.
As I said above, none of these studies looked at hair follicles or the skin cells in the scalp and I can't guarantee that the same effects will be found in them but these substances do have affects on PGD2 and COX-2 so could have the same effects in the scalp.
Quercetin
Quercetin is a flavonoid found in many plants and foods. Tea contains very high amounts compared with other foods (9). Green and black tea leaves when dry contain a mean average of between 204 and 264 mg/100g. Decaffeinated tea contains more than ordinary. But Oolong contains hardly any - less than 2mg/100g. Use as little water as possible when infusing the tea or other substances. When tea is brewed normally, with lots of water, 100g only contains about 2mg of quercetin. Naturally, most of the cup of tea is water. So just use enough water to cover the leaves and mash them and squeeze them to get as much out as possible and then you'll approach the 200-odd mg/100g found in dry tea leaves. This will make a stronger, more concentrated, infusion so that you will only need to use perhaps a teaspoonful on your scalp - depending on the size of the bald patch.
There is some confusion about how soluble quercetin is in water. This is because it comes in 2 forms: quercetin aglycone and quercetin glycoside. 'Aglycone' means 'without sugar' and 'glycoside' means 'with sugar'. It's a bit more complicated than that but, not being a biochemist and not wanting to bore you more than I usually do, we'll just leave it at that. Most of the quercetin in foods is the glycoside form but some parts of some foods contain more of the aglycone form. The flesh of onions and shallots, like other food sources, contain mostly the glycoside form (about 90%) but their skins contain about 80% aglycone. It is only the aglycone form that is not soluble in water (although it is a bit more soluble in hot water). The glycoside form is soluble in water and that is the predominant form in tea.
Ginger
Ginger should be cut into small pieces and heated in water. Again, use as little water as possible to obtain a strong infusion.
Ginger contains many constituents. The main one, gingerol, is transformed into shogaols when it is dried or cooked. The study referred to as number 4 used a methanol (alcohol) extract of ginger. This contained various gingerols, shogaols, gingerdiones and other constituents of ginger. One form of gingerol and two of shogaols inhibited COX-2. Luckily, both water and alcohol can be used to extract the constituents of ginger so you can use water to avoid any potential problems of applying alcohol to your skin.
I must point out that a patent was applied for a number of years ago to use a special preparation of ginger extracts as a hair growth inhibitor but this was for body hair. I'm not sure if it was ever put into production nor how successful it would be as a body hair inhibitor. Body hair and scalp hair are affected by different things and, even if it was successful in its intended use, I don't think it would have an inhibitory effect on scalp hair. But that is only my opinion and is not based on any evidence.
Another thing to be aware of is that COX-2 is also involved in the production of another prostaglandin called PGE2, and this is necessary for skin health. Something that interferes with the production or activity of COX-2 might also interfere with PGE2. So, you would have to weigh up the chances of reduced skin health in your pursuit of more hair. Although if you manage to grow some hair it will cover up any dry or flaky skin that might be caused by lack of PGE2.
Many substances have a low permeability through the skin and they need something to help them penetrate deeply enough to have an effect on the skin cells. It's mainly the outer layer of skin, the stratum corneum, that is the barrier. Some oils can provide that permeability to get through the stratum corneum. So can ethanol (alcohol) but I don't think it's a good idea to put alcohol on the skin. It is an irritant for some people and possibly carcinogenic. A study into ways of making formulations more easily absorbed by human skin found that a mixture of 10% jojoba oil and 30% corn germ oil gave the best penetration of the vegetable oils tested.(10). This was made into an emulsion with water. Emulsions are a combination of two liquids that normally wouldn't be able to mix but do so with the addition of an emulsifier. .
I think an emulsion would be the best way of delivering one of our substances to the scalp cells. Make an infusion with hot water and then add an emulsifier such as lecithin and then add a mixture of 25% jojoba oil and 75% corn germ oil. There should be about half water and half oil.
Tocopherols also inhibited COX-2, as was found in the study in reference 3, above. Both alpha- and gamma- tocopherol showed this ability. They are two of the forms of vitamin E. In the study of skin penetration enhancers, olive oil performed the worst. It is one of the main sources of alpha-tocopherol. Corn germ oil is one of the main sources of gamma-tocopherol and, as it shows such good penetration power, is the one to use.
Lecithin, mentioned above, usually comes in granules but liquid lecithin is also available. If you use the granules make sure they dissolve properly in the water.
Making the hair loss prevention lotion
Distilled water would be better than tap water but if you use water from the tap it would be better to filter it. Make the infusion of your choice - tea or ginger - and make it strong with very little water. When you've done that and you've mashed and strained out the tea leaves or ginger pieces, add the lecithin and stir it until it dissolves. Then add the oil a little bit at a time and stir until the oil and water have mixed and formed a creamy texture. Only make enough for a few days so the mixture will always be fresh. If using ginger, cut the pieces as small as you can get them so more of the active ingredients will be absorbed by the water.
I'm sorry if the negative possibilities have dampened any initial enthusiasm but any pharmaceutical product they bring out will also have drawbacks and potentially harmful side effects.
Try this at your own risk or, to put it another way (and I couldn't resist saying this), on your own head be it.
Curcumin, a constituent of turmeric, looked very promising when I first started researching this. Like quercetin, ginger and aspirin it inhibited the production of COX-2 and I wrote at length about it. Then further research turned up the fact that it is used to make a paste for the removal of body hair. It is used a lot for this purpose in India. Apparently, it works by weakening the hair roots. So that idea had to be consigned to the scrap heap. Never mind. If there's any merit in this idea of using common household items to stop hair loss there should be enough power in the other three substances to do the job.
References
1. Science Translational Medicine 2012 Mar 21;4(126):126ra34.
Prostaglandin d2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.
2. Cancer Chemotherapy and Pharmacology. 2006 Dec;58(6):816-25.
Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin.
3. Mutatation Research. 2004 Jul 13;551(1-2):245-54.
Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription.
4. Fitoterapia. 2011 Jan;82(1):38-43.
Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale).
5. Prostaglandins, Leukotrienes and Medicine. 1984 Feb;13(2):227-35.
Effects of aqueous extracts of onion, garlic and ginger on platelet aggregation and metabolism of arachidonic acid in the blood vascular system: in vitro study.
6. Proceedings of the National Academy of Sciences of the U S A. 1991 Mar 15;88(6):2384-7.
Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells.
7. Proceedings of the National Academy of Sciences of the U S A. 1999 Apr 27;96(9):5292-7.
Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate.
8. Proceedings of the National Academy of Sciences of the U S A. 1987 Mar;84(5):1417-20.
Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity.
9. USDA Database for the Flavonoid Content of Selected Foods, March 2003.
10. Journal of Cosmetic Science. 2007 May-Jun;58(3):245-54.
Vehicle and enhancer effects on human skin penetration of aminophylline from cream formulations: evaluation in vivo.
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Their are a few easy to obtain options above with links to studies etc for anyone wanting to try somthing now.
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So basically mixing this:
http://www.amazon.com/Natures-Answer-Ginger-Root-1-Ounce/dp/B00014HPD0
with some jojoba oil and water.... is going to be good for the hair?
ehh **** this ****... I'm out of here until something real happens... checking this forum everyday is making me lose more hair than AA.
http://www.amazon.com/Natures-Answer-Ginger-Root-1-Ounce/dp/B00014HPD0
with some jojoba oil and water.... is going to be good for the hair?
ehh **** this ****... I'm out of here until something real happens... checking this forum everyday is making me lose more hair than AA.