Quadzilla99
Established Member
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- 14
Newly Discovered Factor in Androgenetic Alopecia. The Cure is Near?
- Thread starter yassin
- Start date
squeegee
Banned
- Reaction score
- 132
Guys.. let's get this thread moving again!!... been slow lately since the upgrade.. Anybody has to report anything so far from any treatments?:salut: I highly suggest to read the thread again...good refresh!!
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[h=1]Nitric oxide synthase/COX cross-talk: nitric oxide activates COX-1 but inhibits COX-2-derived prostaglandin production.[/h]Clancy R, Varenika B, Huang W, Ballou L, Attur M, Amin AR, Abramson SB.
[h=3]Source[/h]Department of Rheumatology, Hospital for Joint Diseases and Division of Rheumatology, New York University School of Medicine, New York, NY 10003, USA.
[h=3]Abstract[/h]It is recognized that there is molecular cross-talk between the inflammatory mediators NO and PGs that may regulate tissue homeostasis and contribute to pathophysiological processes. However, the literature is divided with respect to whether NO activates or inhibits PG production. In this study, we sought to determine whether conflicting observations could be accounted for by divergent effects of NO on the two cyclooxygenase (COX) isoforms. Exposure of resting macrophages to NO (30 microM) enhanced PGE2 release by 4. 5-fold. This enhancement was inhibited by indomethacin but not by the COX-2 selective inhibitor NS398. To separate the activation of phospholipase A2 and COX, we performed experiments using fibroblasts derived from COX-1-deficient or COX-2-deficient mice. These cells exhibit increased basal PG production, which is due to a constitutively stimulated cytosolic phospholipase A2 and enhanced basal expression of the remaining COX isozyme. The exposure of COX- 2-deficient cells to exogenous NO (10 microM) resulted in a 2.4-fold increase of PGE2 release above controls. Further studies indicated that NO stimulated PGE2 release in COX-2-deficient cells, without altering COX-1 mRNA or protein expression. In contrast, NO inhibited COX-2-derived PGE2 production in both LPS-stimulated macrophages and COX-1 knockout cells. This inhibition was associated with both decreased expression and nitration of COX-2. Thus, these studies demonstrate divergent effects of NO on the COX isoforms. The regulation of PGE production by NO is therefore complex and will depend on the local environment in which these pleiotropic mediators are produced.
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[h=1]Nitric oxide synthase/COX cross-talk: nitric oxide activates COX-1 but inhibits COX-2-derived prostaglandin production.[/h]Clancy R, Varenika B, Huang W, Ballou L, Attur M, Amin AR, Abramson SB.
[h=3]Source[/h]Department of Rheumatology, Hospital for Joint Diseases and Division of Rheumatology, New York University School of Medicine, New York, NY 10003, USA.
[h=3]Abstract[/h]It is recognized that there is molecular cross-talk between the inflammatory mediators NO and PGs that may regulate tissue homeostasis and contribute to pathophysiological processes. However, the literature is divided with respect to whether NO activates or inhibits PG production. In this study, we sought to determine whether conflicting observations could be accounted for by divergent effects of NO on the two cyclooxygenase (COX) isoforms. Exposure of resting macrophages to NO (30 microM) enhanced PGE2 release by 4. 5-fold. This enhancement was inhibited by indomethacin but not by the COX-2 selective inhibitor NS398. To separate the activation of phospholipase A2 and COX, we performed experiments using fibroblasts derived from COX-1-deficient or COX-2-deficient mice. These cells exhibit increased basal PG production, which is due to a constitutively stimulated cytosolic phospholipase A2 and enhanced basal expression of the remaining COX isozyme. The exposure of COX- 2-deficient cells to exogenous NO (10 microM) resulted in a 2.4-fold increase of PGE2 release above controls. Further studies indicated that NO stimulated PGE2 release in COX-2-deficient cells, without altering COX-1 mRNA or protein expression. In contrast, NO inhibited COX-2-derived PGE2 production in both LPS-stimulated macrophages and COX-1 knockout cells. This inhibition was associated with both decreased expression and nitration of COX-2. Thus, these studies demonstrate divergent effects of NO on the COX isoforms. The regulation of PGE production by NO is therefore complex and will depend on the local environment in which these pleiotropic mediators are produced.
Quadzilla99
Established Member
- Reaction score
- 14
Dunno why I didn't think of this earlier but in relation to both of these questions...nitrates are pretty safe. I didn't read odalbak's question clearly... They are all the rage in the bodybuilding circles nowadays because they are supposedly the one true supplement that raises nitric oxide levels. Arginine was supposed to do that but it was a complete failure and recent studies show its worthless from that perspectiive...many bbers take nitrates in the form of creatine nitrate to increase NO but you can just take Potassium Nitrate or any or nitrate 45-60 minutes pre workout with 250 mg Vitamin C to achieve a significant increase in NO. This is the one I use: http://www.nutriguard.com/vitamin-store/minerals/54-potassium-nitrate.html
Here's an awesome science filled thread which covers this whole topic and is a great read: (http://forum.bodybuilding.com/showthread.php?t=124049701&highlight=arginine)
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If you read the second post in that thread they talk about how you may be able to ingest a high amount of nitrates via a veggie filled diet and enhance NO that way if you so choose.
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I forgot to mention, the rationale behind taking vitamin C with the nitrates is twofold; to prevent tolerance and to prevent the nitrates from forming nitrosamines in the gut...but I remember reading the danger of nitrates becoming nitrosamine and causing health problems was overrated. Current research is showing nitrates to beneficial to health overall.
squeegee
Banned
- Reaction score
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[h=1]Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells.[/h]Osterlund KL, Handa RJ, Gonzales RJ.
[h=3]Source[/h]Dept. of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, USA.
[h=3]Abstract[/h]Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1beta. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1beta, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell.
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[h=1]Dihydrotestosterone stimulates cerebrovascular inflammation through NFkappaB, modulating contractile function.[/h]Gonzales RJ, Duckles SP, Krause DN.
[h=3]Source[/h]Department of Basic Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona 85004, USA. [email protected]
[h=3]Abstract[/h]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-kappaB (NFkappaB) 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 NFkappaB activation in cerebral arteries and increased levels of the proinflammatory products of NFkappaB 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 NFkappaB-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.
[h=3]Source[/h]Dept. of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, USA.
[h=3]Abstract[/h]Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1beta. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1beta, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell.
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[h=1]Dihydrotestosterone stimulates cerebrovascular inflammation through NFkappaB, modulating contractile function.[/h]Gonzales RJ, Duckles SP, Krause DN.
[h=3]Source[/h]Department of Basic Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona 85004, USA. [email protected]
[h=3]Abstract[/h]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-kappaB (NFkappaB) 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 NFkappaB activation in cerebral arteries and increased levels of the proinflammatory products of NFkappaB 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 NFkappaB-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.
LawOfThelema
Experienced Member
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have you posted the study that showed DHT was inflammatory under conditions of hypoxia but anti inflammatory under normoxia
squeegee
Banned
- Reaction score
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have you posted the study that showed DHT was inflammatory under conditions of hypoxia but anti inflammatory under normoxia
Vascular inflammation plays a key role in the etiology of cardiovascular disease, particularly stoke. Vascular inflammation is under the control of several transcription factors, including nuclear factor kappa B and hypoxia inducible factor-1 alpha (HIF-1α). Activation of these transcription factors can lead to the production of inflammatory mediators such as cyclooxygenase-2 (COX-2). COX-2 plays a role in vascular inflammation, cerebral ischemia-induced injury, and has been implicated as a source of reactive oxygen species (ROS). Inflammatory mediators, such as endotoxin or cellular breakdown products released following injury, are known to signal through the Toll-like receptor 4 (TLR4). TLR4 activation leads to NFκB activation and subsequent production of COX-2. Like COX-2, TLR4 has also been implicated in injury-induced oxidative stress and cerebral ischemia damage. Previous studies have demonstrated that gonadal steroid hormones can also modulate vascular inflammation. Both protective and detrimental effects of androgens on the cardiovascular system have been reported. Since the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) can be converted to 3β-diol, an estrogen receptor (ER) β-selective agonist, I hypothesized that ERβ may mediate some of the protective effects of androgens, while the AR may mediate some of the detrimental effects. The overall goal of this dissertation was to determine the mechanisms by which androgens can influence the vascular inflammatory response under both physiological and pathophysiological conditions. The hypothesis to be tested was that DHT influences vascular inflammation under both physiological and pathophysiological conditions. In my first set of experiments, using Western blot, I found that DHT increases expression of the vascular inflammatory mediator COX-2 under physiological conditions in human coronary artery vascular smooth muscle (VSM) cells and human brain VSM cells. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. This data indicates that the pro-inflammatory effect of DHT under normal physiological conditions is AR mediated. In my second set of experiments, I examined the effects of DHT on vascular inflammation under a variety of pathophysiological conditions. Surprisingly, I found that DHT decreased cytokine-induced COX-2 expression and oxidative stress, endotoxin-induced COX-2 and TLR4 expression in human VSM cells. Furthermore, DHT also decreased hypoxia induced HIF-1α and COX-2 expression in human brain VSM cells and rat pial arteries. Finally, I found that DHT decreased hypoxia with glucose deprivation (HGD)-induced HIF-1α, COX-2 and TLR4 expression in human brain VSM cells. DHT`s anti-inflammatory effects during cytokine or HGD-induced inflammation in human brain VSM cells were not blocked by the AR antagonist bicalutamide, indicating that they were not AR mediated. These results led me to my second hypothesis, that DHT's anti-inflammatory effects are ERβ-mediated. In my third set of experiments, I found that the DHT metabolite/ERβ selective agonist 3β-diol also decreased cytokine-induced COX-2 expression in human brain VSM cells. Furthermore, DHT's ability to reduce cytokine-induced COX-2 expression in human brain VSM cells was inhibited by the non-selective estrogen receptor antagonist ICI 182,780 and the selective ERβ antagonist PHTPP. The mRNAs for steroid metabolizing enzymes in the pathway necessary to convert DHT to 3β-diol were detected in human brain VSM cells, as were AR and ERβ mRNAs. Therefore, DHT appears to be protective against cerebrovascular inflammation via conversion to 3β-diol and subsequent activation of ERβ in human brain VSM cells. The results of these studies indicate that: 1) DHT increases COX-2 expression under unstimulated/physiological conditions via an AR-dependent mechanism. 2) DHT decreases cytokine-, endotoxin,-hypoxia, and HGD-induced COX-2 expression via an AR-independent mechanism. 3) DHT decreases cytokine-induced reactive oxygen species. 4) DHT decreases hypoxia-induced HIF-1α expression. 5) DHT decreases HIF-1α and TLR4 expression during HGD via an AR-independent mechanism. 6) DHT's effect to attenuate cytokine-induced COX-2 expression is ERβ-mediated.
???? this one?
LawOfThelema
Experienced Member
- Reaction score
- 18
I actually got it the wrong way around
http://ajpheart.physiology.org/content/early/2011/08/15/ajpheart.00446.2011.abstract
Dihydrotestosterone Attenuates Hypoxia Inducible Factor-1alpha and Cyclooxygenase-2 in Cerebral Arteries during Hypoxia or Hypoxia with Glucose Deprivation
+ Author Affiliations
Abstract
Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1alpha (HIF-1α) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1α and COX-2 following hypoxia or hypoxia with glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1α levels were assessed via western blot and HIF-1α activation was indirectly measured via a DNA binding assay. Experiments were performed using cerebral arteries isolated from castrated male rats treated in vivo with placebo or DHT (18 days) followed by hypoxic exposure ex vivo (1% O2), cerebral arteries isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100 nM; 6 h) then exposed to hypoxia ex vivo (1% O2), or primary human brain vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (Cells 51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF-1α. Following hypoxia or HGD, HIF-1α and COX-2 levels were increased; this response was blunted by DHT (Cells HGD: -47% COX-2, -34% HIF-1α; Cells hypoxia: -29% COX-2, -54% HIF-1α; arteries ex vivo: -37% COX-2; arteries in vivo: -35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced HIF-1α DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: -55%). These results demonstrate that upregulation of COX-2 and HIF-1α in response to hypoxia is suppressed by DHT via an androgen receptor independent mechanism.
http://ajpheart.physiology.org/content/early/2011/08/15/ajpheart.00446.2011.abstract
Dihydrotestosterone Attenuates Hypoxia Inducible Factor-1alpha and Cyclooxygenase-2 in Cerebral Arteries during Hypoxia or Hypoxia with Glucose Deprivation
+ Author Affiliations
- [SUP]1[/SUP]University of Arizona-Phoenix
- ↵* University of Arizona-Phoenix [email protected]
- Submitted 4 May 2011.
- Revision received 1 August 2011.
- Accepted 9 August 2011.
Abstract
Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1alpha (HIF-1α) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1α and COX-2 following hypoxia or hypoxia with glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1α levels were assessed via western blot and HIF-1α activation was indirectly measured via a DNA binding assay. Experiments were performed using cerebral arteries isolated from castrated male rats treated in vivo with placebo or DHT (18 days) followed by hypoxic exposure ex vivo (1% O2), cerebral arteries isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100 nM; 6 h) then exposed to hypoxia ex vivo (1% O2), or primary human brain vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (Cells 51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF-1α. Following hypoxia or HGD, HIF-1α and COX-2 levels were increased; this response was blunted by DHT (Cells HGD: -47% COX-2, -34% HIF-1α; Cells hypoxia: -29% COX-2, -54% HIF-1α; arteries ex vivo: -37% COX-2; arteries in vivo: -35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced HIF-1α DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: -55%). These results demonstrate that upregulation of COX-2 and HIF-1α in response to hypoxia is suppressed by DHT via an androgen receptor independent mechanism.
squeegee
Banned
- Reaction score
- 132
PGD2 showed anti-hypoxic effects in numerous studies!!!!!!!!! Androgen Alopecia! What a puzzle!!!!
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[h=1]Use of minoxidil to demonstrate that prostacyclin is not the mediator of bone resorption stimulated by growth factors in mouse calvariae.[/h]Tashjian AH Jr, Bosma TJ, Levine L.
[h=3]Source[/h]Laboratory of Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.
[h=3]Abstract[/h]Growth factors, such as human transforming growth factor-alpha (hTGF alpha) and epidermal growth factor, as well as human tumor necrosis factor (hTNF) stimulate the resorption of bone in neonatal mouse calvariae in organ culture via a prostaglandin (PG)-mediated pathway. In response to such factors mouse calvariae produce substantial quantities of prostaglandin E2 (PGE2) and prostacyclin (PGI2). We have selectively inhibited the production of PGI2, but not PGE2, using the drug minoxidil and have measured the effects on stimulated bone resportion and arachidonic acid metabolism. The increased production of 6-keto-PGF1 alpha (6k-PGF1 alpha), the hydrolytic product of PGI2, stimulated by recombinant hTGF alpha and hTNF as well as murine epidermal growth factor was inhibited by minoxidil. There was no inhibition by minoxidil of PGE2 production. Despite essentially complete inhibition of stimulated 6k-PGF1 alpha formation, there was no inhibition of bone resorption. The possibility was investigated that growth factors and TNF enhanced enzymatic conversion of PGI2 to 6k-PGE1, which stimulates bone resorption in mouse calvariae with a potency about one fourth that of PGE2. Enzymatic conversion of PGI2 to 6k-PGE1 is inhibited by rutin. Rutin did not inhibit bone resorption stimulated by hTGF alpha or hTNF. We conclude, on the basis of these new results and previously published data, that the cyclooxygenase product that acts as the mediator of bone resorption enhanced by growth factors and TNF in mouse calvariae is probably PGE2.
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[h=1]Use of minoxidil to demonstrate that prostacyclin is not the mediator of bone resorption stimulated by growth factors in mouse calvariae.[/h]Tashjian AH Jr, Bosma TJ, Levine L.
[h=3]Source[/h]Laboratory of Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.
[h=3]Abstract[/h]Growth factors, such as human transforming growth factor-alpha (hTGF alpha) and epidermal growth factor, as well as human tumor necrosis factor (hTNF) stimulate the resorption of bone in neonatal mouse calvariae in organ culture via a prostaglandin (PG)-mediated pathway. In response to such factors mouse calvariae produce substantial quantities of prostaglandin E2 (PGE2) and prostacyclin (PGI2). We have selectively inhibited the production of PGI2, but not PGE2, using the drug minoxidil and have measured the effects on stimulated bone resportion and arachidonic acid metabolism. The increased production of 6-keto-PGF1 alpha (6k-PGF1 alpha), the hydrolytic product of PGI2, stimulated by recombinant hTGF alpha and hTNF as well as murine epidermal growth factor was inhibited by minoxidil. There was no inhibition by minoxidil of PGE2 production. Despite essentially complete inhibition of stimulated 6k-PGF1 alpha formation, there was no inhibition of bone resorption. The possibility was investigated that growth factors and TNF enhanced enzymatic conversion of PGI2 to 6k-PGE1, which stimulates bone resorption in mouse calvariae with a potency about one fourth that of PGE2. Enzymatic conversion of PGI2 to 6k-PGE1 is inhibited by rutin. Rutin did not inhibit bone resorption stimulated by hTGF alpha or hTNF. We conclude, on the basis of these new results and previously published data, that the cyclooxygenase product that acts as the mediator of bone resorption enhanced by growth factors and TNF in mouse calvariae is probably PGE2.
zombiehair
Member
- Reaction score
- 3
Hi all
just checking in here .Ive almost used up my first 60 ml bottle of kirkland minoxidil that i had added 10ml thyme oil.
I apply this in the evenings .when i began this experiment the application almost instantly induced a warming burning sensation.
scared me a bit so i added some castor or emu oil to the mix before application.
since then i have tried a neat application again and although i still get the warm burning sensation it is a good bit less than at the begining.
no negative or positive results to report.
In the mornings i need somthing quick drying and undetectable so i can wash and go to work
what i have been using is minoxidol foam and a small amount of miconazole.
to prepare this i would half fill a shot glass with boiling water let sit for a bit then pour out the water .
this warms the glass so when i add some minoxidol foam onto the miconazole the mixture quickly melts into a liquid .
Thinking about replacing the miconazole with an ibuprofen gel not sure.
i got some ibuleve a maximum strength 10% ibuprofen gel.
any ways no change negative or positive to report ,still early days.
good luck all.
just checking in here .Ive almost used up my first 60 ml bottle of kirkland minoxidil that i had added 10ml thyme oil.
I apply this in the evenings .when i began this experiment the application almost instantly induced a warming burning sensation.
scared me a bit so i added some castor or emu oil to the mix before application.
since then i have tried a neat application again and although i still get the warm burning sensation it is a good bit less than at the begining.
no negative or positive results to report.
In the mornings i need somthing quick drying and undetectable so i can wash and go to work
what i have been using is minoxidol foam and a small amount of miconazole.
to prepare this i would half fill a shot glass with boiling water let sit for a bit then pour out the water .
this warms the glass so when i add some minoxidol foam onto the miconazole the mixture quickly melts into a liquid .
Thinking about replacing the miconazole with an ibuprofen gel not sure.
i got some ibuleve a maximum strength 10% ibuprofen gel.
any ways no change negative or positive to report ,still early days.
good luck all.
squeegee
Banned
- Reaction score
- 132
Each time I add PGE1 to the mix.. I have regrowth. Minoxidil, Miconazole Nitrate or Nitroglycerin cream all upregulates PGE1. PGE1 is the major hair growth booster from the prostaglandins family. DGLA is the immediate precursor of PGE1. (Prostaglandin E1).PGE1 counteracts PGE2 as well.
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Really interesting link:Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders http://www.hindawi.com/journals/jar/2012/121390/#B145
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Really interesting link:Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders http://www.hindawi.com/journals/jar/2012/121390/#B145
Quadzilla99
Established Member
- Reaction score
- 14
"You must spread some Reputation around before giving it to squeegee again."
squeegee
Banned
- Reaction score
- 132
Hi all
just checking in here .Ive almost used up my first 60 ml bottle of kirkland minoxidil that i had added 10ml thyme oil.
I apply this in the evenings .when i began this experiment the application almost instantly induced a warming burning sensation.
scared me a bit so i added some castor or emu oil to the mix before application.
since then i have tried a neat application again and although i still get the warm burning sensation it is a good bit less than at the begining.
no negative or positive results to report.
In the mornings i need somthing quick drying and undetectable so i can wash and go to work
what i have been using is minoxidol foam and a small amount of miconazole.
to prepare this i would half fill a shot glass with boiling water let sit for a bit then pour out the water .
this warms the glass so when i add some minoxidol foam onto the miconazole the mixture quickly melts into a liquid .
Thinking about replacing the miconazole with an ibuprofen gel not sure.
i got some ibuleve a maximum strength 10% ibuprofen gel.
any ways no change negative or positive to report ,still early days.
good luck all.
Good stuff Zombie hair. Keep the feedback coming!!
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ahhaha Quadzilla bros! I am just passionate or obsess with male pattern baldness...I see it as a challenge! Losing our hair blows , we have to stop whining about it and wait about the so called scientist to find something to medicate us ... Just being pro-active! I can be like any others sheep out there and poor minoxidil on my pumpkin and take finasteride without asking myself why this **** is working! but I just cannot!!!!!!!! we are so close...go damn !!
baldnesssadness
Established Member
- Reaction score
- 4
hi guys... its been 24 days now and i can clearly say cetirizine havent done anything for me... my temples have receeded more now, i am definatly and clearly a norwood 2 right now and i lost so much hair in the shower today , much more than i ever have in my life damn this is depressing... some positive effects i see is vellus hair that is growing lower than my hairline cetirizine has only helped me with the itching problem it made it minimal to nothing , i dont know what to do guys? should continue? i havent had so much hair loss in my life , my clothes, my bed full of hair everytime i touch my scalp some hair is coming ... should i try minoxidil on the temples while im taking cetirizine?
Quadzilla99
Established Member
- Reaction score
- 14
np squeegee....I love reading your posts I've learned a lot from you. Learn something new here everyday. Also, any guy who admits to rubbing vag cream on his scalp has more balls than I could ever have lol I still tell my gf, family, and friends my nizoral and now T-gel greasy regimen is because I have real bad dandruff lol
squeegee
Banned
- Reaction score
- 132
In endothelium, there are six primary cyclooxygenase-(COX-) derived eicosanoids, prostaglandin H2 (PGH2), prostaglandin I2 (PGI2, prostacyclin), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), prostaglandin D2 (PGD2), and thromboxane A2 (TxA2) (Figure 1). These eicosanoids are local hormones that are synthesized by virtually all mammalian tissues [46] and act at or near their sites of synthesis in both autocrine and paracrine fashion. They trigger a vast array of biological signals, among which are vasodilation, vasoconstriction, and platelet aggregation [47–49]. In fact, the eicosanoids were the first identified endothelium-derived vasoactive factors [50, 51]. Although there is conflicting evidence [52–54], the majority of the literature shows that PGI2 and PGD2 are vasodilators [55–59], whereas PGH2, PGF2α, and TxA2 are vasoconstrictors and/or platelet aggregation inducers [53, 54, 60–66]. PGE2 can induce vasodilation [47, 67–70] or vasoconstriction [53, 54, 71–73], depending on the vascular bed and concentration [74, 75]. In healthy endothelium, these vasodilators and vasoconstrictors, coexisting with other vasoactive factors, are held in balance to maintain normal vascular functions. The aging process shifts this balanced profile toward a proconstrictive mediator profile [76, 77]. In this paper, we summarize and discuss how endothelium-derived eicosanoid profile changes with age and how those changes might contribute to age-associated endothelium dysfunction..
http://www.hindawi.com/journals/jar/2012/121390/#B145
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Good thread here: http://www.baldtruthtaIk.com/showthread.php?t=8841 2020 @ it!
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Androgen control of cyclooxygenase expression in the rat epididymis.
Cheuk BL, Leung PS, Lo AC, Wong PY.
Source
Department of Physiology, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong.
Abstract
Bradykinin and a number of peptide hormones such as angiotensin, endothelin, and vasopressin stimulate anion secretion in rat epididymis via local formation of PGE(2). These effects are mediated by cyclooxygenase (COX)-1 isozyme. The present study was undertaken to assess the androgen control of COX expression in the epididymis. Adult male Sprague-Dawley rats were bilaterally castrated through a scrotal route. Reverse transcription-polymerase chain reaction was used to measure COX-1 and COX-2 mRNAs in the epididymis in normal and castrated rats. Anion secretion in epithelia grown from the epididymides of these rats was studied by the short-circuit current technique. In normal rats, COX-1 and COX-2 mRNAs were detected in the intact epididymis. Elimination of spermatozoa by the technique of efferent duct ligation or flushing out spermatozoa did not affect the expression of either enzyme in the epididymis, indicating that the epithelium, but not spermatozoa, expressed the enzymes. Castration caused a time-dependent decrease in expression of COX-1 and COX-2 mRNAs, which were partially restored upon testosterone replacement. In epithelia cultured from castrated rats, there was a complete loss of bradykinin-induced anion secretion. This effect was reversible upon testosterone replacement. Although epithelia from castrated rats did not respond to bradykinin, they could respond to cAMP, forskolin, and PGE(2) with only 20% loss of response magnitude when compared with epithelia from normal rats. These results suggest that the expression of COX-1 and COX-2 are dependent on androgen. The loss of COX-1 expression after castration correlates with the specific loss of anion secretion induced by bradykinin and possibly other hormones.
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In summary, we have shown that DHT increases COX-2 protein levels in the absence of induced inflammation via an AR-dependent mechanism, but attenuates IL-1β-induced increases in COX-2 levels via an AR-independent mechanism, in primary HCASMC. The findings suggest that DHT may be proinflammatory, by augmenting COX-2 levels under physiological conditions, but anti-inflammatory, by attenuating COX-2 under pathophysiological conditions. Surprisingly, the effects of DHT on COX-2 levels did not translate to changes in PGE[SUB]2[/SUB] production, although other COX-2-derived end products (prostacyclin, PGF[SUB]2α[/SUB], and PGD[SUB]2[/SUB]) may prove to be androgen targets. Finally, we found that HCASMC are more responsive (i.e., increases in COX-2) to IL-1β or LPS stimulation than vascular endothelial cells. Investigations of mechanisms associated with inflammatory effects on human vascular smooth muscle cells have been largely ignored in the literature in favor of the more commonly studied vascular endothelial cells. Thus we have identified human vascular smooth muscle cells as potentially important targets for androgens in the vascular response to inflammation. This is of particular importance, because investigation of the mechanisms by which androgens modulate vascular inflammation may lead to better therapeutic targets for cardiovascular diseases, such as atherosclerosis, myocardial infarction, and stroke. http://ajpendo.physiology.org/content/298/4/E838.full
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an involvement of PGD2-
regulated androgen receptor expression in the epididymal
cells as an explanation of the observed effects of COX-2
inhibitors cannot be excluded.
http://www.biolreprod.org/content/66/2/374.full.pdf
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The effect of prostaglandin D2 on rat testicular testosterone levels].
[Article in Japanese]
Yamada K.
Source
Laboratory for Pharmaceutical Education, Tokyo College of Pharmacy, Hachioji, Japan.
Abstract
In vivo effects of prostaglandin D2 (PGD2) on rat testicular testosterone levels were studied. Testosterone levels were determined by HPLC after 6 hours of PGD2 and of hCG. The testosterone levels were decreased by dose of 500 micrograms/rat intraperitoneal injection. Testis testosterone levels were subsequently decreased by intratesticular injection with PGD2 (1.0 micrograms) into the right testis. The left testis received vehicle alone for control. The increase in testosterone levels induced by hCG (50, 100 and 500 unit/rat s.c.) were also inhibited by intraperitoneal injection of 500 micrograms of PGD2. On the other hand, intratesticular injection of hCG (0.01, 0.1 and 1.0 unit/testis) caused an increase in testosterone levels according to dose of hCG. The increase in testosterone levels by hCG was inhibited by simultaneous injection of PGD2 (1.0 micrograms/testis). These results suggest that PGD2 may play an inhibitory action on LH action in androgen synthesis in the rat testis.
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Dihydrotestosterone stimulates cerebrovascular inflammation through NFkappaB, modulating contractile function.
Gonzales RJ, Duckles SP, Krause DN.
Source
Department of Basic Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona 85004, USA. [email protected]
Abstract
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-kappaB (NFkappaB) 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 NFkappaB activation in cerebral arteries and increased levels of the proinflammatory products of NFkappaB 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 NFkappaB-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.
http://www.ncbi.nlm.nih.gov/pubmed/18941467
http://www.hindawi.com/journals/jar/2012/121390/#B145
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Good thread here: http://www.baldtruthtaIk.com/showthread.php?t=8841 2020 @ it!
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Androgen control of cyclooxygenase expression in the rat epididymis.
Cheuk BL, Leung PS, Lo AC, Wong PY.
Source
Department of Physiology, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong.
Abstract
Bradykinin and a number of peptide hormones such as angiotensin, endothelin, and vasopressin stimulate anion secretion in rat epididymis via local formation of PGE(2). These effects are mediated by cyclooxygenase (COX)-1 isozyme. The present study was undertaken to assess the androgen control of COX expression in the epididymis. Adult male Sprague-Dawley rats were bilaterally castrated through a scrotal route. Reverse transcription-polymerase chain reaction was used to measure COX-1 and COX-2 mRNAs in the epididymis in normal and castrated rats. Anion secretion in epithelia grown from the epididymides of these rats was studied by the short-circuit current technique. In normal rats, COX-1 and COX-2 mRNAs were detected in the intact epididymis. Elimination of spermatozoa by the technique of efferent duct ligation or flushing out spermatozoa did not affect the expression of either enzyme in the epididymis, indicating that the epithelium, but not spermatozoa, expressed the enzymes. Castration caused a time-dependent decrease in expression of COX-1 and COX-2 mRNAs, which were partially restored upon testosterone replacement. In epithelia cultured from castrated rats, there was a complete loss of bradykinin-induced anion secretion. This effect was reversible upon testosterone replacement. Although epithelia from castrated rats did not respond to bradykinin, they could respond to cAMP, forskolin, and PGE(2) with only 20% loss of response magnitude when compared with epithelia from normal rats. These results suggest that the expression of COX-1 and COX-2 are dependent on androgen. The loss of COX-1 expression after castration correlates with the specific loss of anion secretion induced by bradykinin and possibly other hormones.
- - - Updated - - -
In summary, we have shown that DHT increases COX-2 protein levels in the absence of induced inflammation via an AR-dependent mechanism, but attenuates IL-1β-induced increases in COX-2 levels via an AR-independent mechanism, in primary HCASMC. The findings suggest that DHT may be proinflammatory, by augmenting COX-2 levels under physiological conditions, but anti-inflammatory, by attenuating COX-2 under pathophysiological conditions. Surprisingly, the effects of DHT on COX-2 levels did not translate to changes in PGE[SUB]2[/SUB] production, although other COX-2-derived end products (prostacyclin, PGF[SUB]2α[/SUB], and PGD[SUB]2[/SUB]) may prove to be androgen targets. Finally, we found that HCASMC are more responsive (i.e., increases in COX-2) to IL-1β or LPS stimulation than vascular endothelial cells. Investigations of mechanisms associated with inflammatory effects on human vascular smooth muscle cells have been largely ignored in the literature in favor of the more commonly studied vascular endothelial cells. Thus we have identified human vascular smooth muscle cells as potentially important targets for androgens in the vascular response to inflammation. This is of particular importance, because investigation of the mechanisms by which androgens modulate vascular inflammation may lead to better therapeutic targets for cardiovascular diseases, such as atherosclerosis, myocardial infarction, and stroke. http://ajpendo.physiology.org/content/298/4/E838.full
- - - Updated - - -
an involvement of PGD2-
regulated androgen receptor expression in the epididymal
cells as an explanation of the observed effects of COX-2
inhibitors cannot be excluded.
http://www.biolreprod.org/content/66/2/374.full.pdf
- - - Updated - - -
The effect of prostaglandin D2 on rat testicular testosterone levels].
[Article in Japanese]
Yamada K.
Source
Laboratory for Pharmaceutical Education, Tokyo College of Pharmacy, Hachioji, Japan.
Abstract
In vivo effects of prostaglandin D2 (PGD2) on rat testicular testosterone levels were studied. Testosterone levels were determined by HPLC after 6 hours of PGD2 and of hCG. The testosterone levels were decreased by dose of 500 micrograms/rat intraperitoneal injection. Testis testosterone levels were subsequently decreased by intratesticular injection with PGD2 (1.0 micrograms) into the right testis. The left testis received vehicle alone for control. The increase in testosterone levels induced by hCG (50, 100 and 500 unit/rat s.c.) were also inhibited by intraperitoneal injection of 500 micrograms of PGD2. On the other hand, intratesticular injection of hCG (0.01, 0.1 and 1.0 unit/testis) caused an increase in testosterone levels according to dose of hCG. The increase in testosterone levels by hCG was inhibited by simultaneous injection of PGD2 (1.0 micrograms/testis). These results suggest that PGD2 may play an inhibitory action on LH action in androgen synthesis in the rat testis.
- - - Updated - - -
Dihydrotestosterone stimulates cerebrovascular inflammation through NFkappaB, modulating contractile function.
Gonzales RJ, Duckles SP, Krause DN.
Source
Department of Basic Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona 85004, USA. [email protected]
Abstract
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-kappaB (NFkappaB) 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 NFkappaB activation in cerebral arteries and increased levels of the proinflammatory products of NFkappaB 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 NFkappaB-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.
http://www.ncbi.nlm.nih.gov/pubmed/18941467
LawOfThelema
Experienced Member
- Reaction score
- 18
so lets recap. what did find that we CAN USE TO COMBAT prostaglandin d2. all this information concerning this stuff is great, but at some point we need to try things.
off the top of my head aloe vera contains salicylic acid. ive seen people mention using it topically or internally for their baldness. israelite said drinking the stuff helps to reduce his shed.
off the top of my head aloe vera contains salicylic acid. ive seen people mention using it topically or internally for their baldness. israelite said drinking the stuff helps to reduce his shed.
squeegee
Banned
- Reaction score
- 132
[h=1]COX-2-mediated PGD2 synthesis regulates phosphatidylcholine biosynthesis in rat renal papillary tissue.[/h]Fernández-Tome M, Kraemer L, Federman SC, Favale N, Speziale E, Sterin-Speziale N.
[h=3]Source[/h]Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Junin, 1113, Buenos Aires, Argentina. [email protected]
[h=3]Abstract[/h]Phosphatidylcholine (PC) is the major membrane phospholipid in mammalian cells. Previous works from our laboratory demonstrated a close metabolic relationship between the maintenance of PC biosynthesis and the prostaglandins endogenously synthesized by cyclooxygenase (COX) in rat renal papilla. In the present work, we studied the COX isoform involved in papillary PC biosynthesis regulation. The incorporation of [methyl-3H]choline and [32P]orthophosphate to PC was determined in the absence and presence of SC-560 and NS-398, COX-1 and COX-2 specific inhibitors. PC synthesis was highly sensitive to COX-2 inhibition, while COX-1 inhibition only reduced PC synthesis at high SC-560 concentration. The analysis of choline-containing metabolites showed that COX-2 inhibition affected the formation of CDP-choline intermediary. The evaluation of PC biosynthetic enzymes revealed that microsomal, as well as nuclear, CTPhosphocholine cytidylyltransferase (CCT), and nuclear-CDP-choline:1,2-diacylglycerol cholinephosphotransferase (CTP) activities were affected by COX-2 inhibition. The addition of exogenous prostaglandin D(2) (PGD(2)) restored nuclear-CCT and -CPT activities but not microsomal CCT. Papillary synthesis of PGD(2) was only detected in nuclear fraction where it was blocked by COX-2 inhibitor NS-398, but not by COX-1 inhibitor. All together, the present results demonstrated that COX-2-mediated PGD(2) synthesis is a PC biosynthesis regulator in rat renal papilla. Considering the importance of the maintenance of PC biosynthesis for the preservation of cell membrane homeostasis to ensure cell viability, and the extensive use of COX-2 inhibitors in therapeutics, the present results could have great pharmacological implications, and can constitute a biochemical explanation for the nephrotoxic effect of non-steroidal anti-inflammatory drugs.
[h=3]Source[/h]Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, IQUIFIB-CONICET, Junin, 1113, Buenos Aires, Argentina. [email protected]
[h=3]Abstract[/h]Phosphatidylcholine (PC) is the major membrane phospholipid in mammalian cells. Previous works from our laboratory demonstrated a close metabolic relationship between the maintenance of PC biosynthesis and the prostaglandins endogenously synthesized by cyclooxygenase (COX) in rat renal papilla. In the present work, we studied the COX isoform involved in papillary PC biosynthesis regulation. The incorporation of [methyl-3H]choline and [32P]orthophosphate to PC was determined in the absence and presence of SC-560 and NS-398, COX-1 and COX-2 specific inhibitors. PC synthesis was highly sensitive to COX-2 inhibition, while COX-1 inhibition only reduced PC synthesis at high SC-560 concentration. The analysis of choline-containing metabolites showed that COX-2 inhibition affected the formation of CDP-choline intermediary. The evaluation of PC biosynthetic enzymes revealed that microsomal, as well as nuclear, CTP
hosphocholine cytidylyltransferase (CCT), and nuclear-CDP-choline:1,2-diacylglycerol cholinephosphotransferase (CTP) activities were affected by COX-2 inhibition. The addition of exogenous prostaglandin D(2) (PGD(2)) restored nuclear-CCT and -CPT activities but not microsomal CCT. Papillary synthesis of PGD(2) was only detected in nuclear fraction where it was blocked by COX-2 inhibitor NS-398, but not by COX-1 inhibitor. All together, the present results demonstrated that COX-2-mediated PGD(2) synthesis is a PC biosynthesis regulator in rat renal papilla. Considering the importance of the maintenance of PC biosynthesis for the preservation of cell membrane homeostasis to ensure cell viability, and the extensive use of COX-2 inhibitors in therapeutics, the present results could have great pharmacological implications, and can constitute a biochemical explanation for the nephrotoxic effect of non-steroidal anti-inflammatory drugs.
odalbak
Established Member
- Reaction score
- 11
Interesting. Where did you get that table squeegee?
Maybe increasing the consumption of Omega-3 oil and reducing the Omega-6 intake from my diet could play a beneficial factor, not only for my mental health I know that, but maybe for my hair as well… ?
squeegee
Banned
- Reaction score
- 132
COX-inhibiting nitric oxide donator
From Wikipedia, the free encyclopedia
Jump to: navigation, search
COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of non-steroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.
These compounds were first described by John Wallace[SUP][1][/SUP] and colleagues. CINODs are compounds generated by the fusion of an existing NSAID with a nitric oxide (NO)-donating moiety by chemical means, usually by ester linkage. CINODs retain the anti-inflammatory efficacy of NSAIDs via inhibition of cyclooxygenase (COX) while arguably improving upon gastric and vascular safety, most likely via vasorelaxation, inhibition of leukocyte adhesion and inhibition of caspases, all known effects of NO.
The first CINODs were developed in the 1990s, and as yet none have been approved for use by the general public. The importance of developing such drugs was increased when COX-2-specific NSAIDs rofecoxib (Vioxx) and lumiracoxib (Prexige) were removed from major pharmaceutical markets in the mid-2000s due to vascular safety concerns. In addition, traditional NSAIDs increase blood pressure and interfere with the actions of antihypertensive drugs. Several CINODs are currently being tested in clinical trials, the most advanced of which are being conducted by the French pharmaceutical company NicOx, whose flagship compound naproxcinod (NO-naproxen, nitronaproxen) is in phase III trials for the treatment of osteoarthritis.[SUP][2][/SUP] Naproxcinod is a fusion of naproxen and a NO-donating group. Other CINODs are also being tested by NicOx for the treatment of diseases in which inflammation plays a role.[SUP][3][/SUP]
Pretty cool but the FDA said no to it.. Cox inhibitor + Nitric oxide!
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We need to reduce Cox-2 in the skin so PGD2 goes back as per normal without reducing Cox-1 by preserving or boosting it.. Cox-1 is needed for the production of PGE1.. by using Minoxidil, Miconazole Nitrate...
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Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?
Das UN.
Source
UND Life Sciences, #205, 2477 Overlook Road, Cleveland Heights, OH 44106, USA.
Abstract
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
- - - Updated - - -
From Wikipedia, the free encyclopedia
Jump to: navigation, search
COX-inhibiting nitric oxide donators (CINODs), also known as NO-NSAIDs, are a new class of non-steroidal anti-inflammatory drug (NSAID) developed with the intention of providing greater safety than existing NSAIDs.
These compounds were first described by John Wallace[SUP][1][/SUP] and colleagues. CINODs are compounds generated by the fusion of an existing NSAID with a nitric oxide (NO)-donating moiety by chemical means, usually by ester linkage. CINODs retain the anti-inflammatory efficacy of NSAIDs via inhibition of cyclooxygenase (COX) while arguably improving upon gastric and vascular safety, most likely via vasorelaxation, inhibition of leukocyte adhesion and inhibition of caspases, all known effects of NO.
The first CINODs were developed in the 1990s, and as yet none have been approved for use by the general public. The importance of developing such drugs was increased when COX-2-specific NSAIDs rofecoxib (Vioxx) and lumiracoxib (Prexige) were removed from major pharmaceutical markets in the mid-2000s due to vascular safety concerns. In addition, traditional NSAIDs increase blood pressure and interfere with the actions of antihypertensive drugs. Several CINODs are currently being tested in clinical trials, the most advanced of which are being conducted by the French pharmaceutical company NicOx, whose flagship compound naproxcinod (NO-naproxen, nitronaproxen) is in phase III trials for the treatment of osteoarthritis.[SUP][2][/SUP] Naproxcinod is a fusion of naproxen and a NO-donating group. Other CINODs are also being tested by NicOx for the treatment of diseases in which inflammation plays a role.[SUP][3][/SUP]
Pretty cool but the FDA said no to it.. Cox inhibitor + Nitric oxide!
- - - Updated - - -
We need to reduce Cox-2 in the skin so PGD2 goes back as per normal without reducing Cox-1 by preserving or boosting it.. Cox-1 is needed for the production of PGE1.. by using Minoxidil, Miconazole Nitrate...
- - - Updated - - -
Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids?
Das UN.
Source
UND Life Sciences, #205, 2477 Overlook Road, Cleveland Heights, OH 44106, USA.
Abstract
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke. This has been attributed to their ability to inhibit endothelial COX-2 derived prostacyclin (PGI2) but not platelet COX-1 derived thromboxane A2 (TXA2). On the other hand, aspirin blocks both COX-1 and COX-2 enzymes without decreasing PGI2 but blocks TXA2 synthesis that explains its beneficial action in the prevention of coronary heart disease (CHD). The inhibitory action of aspirin on COX-1 and COX-2 enzymes enhances the tissue concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). These fatty acids form precursors to PGE1, PGI2, PGI3, lipoxins (LXs), and resolvins that have anti-inflammatory actions. In contrast, increase in the concentrations of DGLA, AA, EPA, and DHA is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. COX-2 inhibitors interfere with the formation of LXs and resolvins that have neuroprotective and cardioprotective actions. EPA and PGI2 have anti-arrhythmic action. EPA, DHA, and AA augment eNO formation that prevents atherosclerosis. This suggests that COX-2 inhibitors increase cardiovascular and stroke risk by interfering with the formation of eNO, PGI2, LXs, and resolvins and implies that combining EFAs with COX-2 inhibitors could prevent these complications.
- - - Updated - - -
Interesting. Where did you get that table squeegee?
Maybe increasing the consumption of Omega-3 oil and reducing the Omega-6 intake from my diet could play a beneficial factor, not only for my mental health I know that, but maybe for my hair as well… ?
Straight from Wikipedia.... Sprecher's shunt chart... yep... western diet is highly inflammatory... too much omega 6!!