sara la volta buona?
- Thread starter ciro63vg
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Da quello che leggo in questo link e su un forum americano anche il sodio cromoglicato inibisce pgd2.
http://www.uptodate.com/contents/mast-cells-surface-receptors-and-signal-transduction/abstract/52
Che ne pensate. Si potrebbe usare magari questo prodotto o no?
http://www.in-farmacia.it/cromabak-coll-fl-10ml-20mg_ml.html
Altra domanda poi basta: La nigella sativa assunta oralmente potrebbe servire a qlc?
ciao
http://www.uptodate.com/contents/mast-cells-surface-receptors-and-signal-transduction/abstract/52
Che ne pensate. Si potrebbe usare magari questo prodotto o no?
http://www.in-farmacia.it/cromabak-coll-fl-10ml-20mg_ml.html
Altra domanda poi basta: La nigella sativa assunta oralmente potrebbe servire a qlc?
ciao
http://www.hopkinsmedicine.org/dermatology/news/2012_STM_Garza.pdf
per chi desiderasse leggere l'articolo di cotsarelis in integrale.
per chi desiderasse leggere l'articolo di cotsarelis in integrale.
DISCUSSIONE FINALE:
Recent evidence has illustrated a role for prostaglandins in regulating hair growth. For example, the PGF2a analog latanoprost is Food and Drug Administration (FDA)–approved and routinely used clinically to enhance hair growth of human eyelashes (15). PGE2 has been pro- posed to protect from radiation-induced hair loss in mice (29), and both PGE2 and PGF2a have been shown to enhance hair growth in mice (20). Our studies show that prostaglandins are dysregulated in AGA, the most common type of hair loss in men. Specifically, PGD2 inhibits hair growth and thus represents a negative counterbalance to the pos- itive effects on hair growth shown for PGE2 and PGF2a.
There is precedence for the opposing functions of individual pros- taglandins that are downstream from the PTGS enzymes. For exam- ple, in the lung, PGE2 causes relaxation, whereas PGD2 causes contraction of bronchial muscle tone (16). Our results suggest that in mouse and human skin, a balance between PGE2 and PGD2 controls hair growth. This model predicts then that efforts to reverse alopecia should optimally focus on both enhancing PGE2 and inhibiting PGD2 signaling. This model also explains why agents such as aspirin, which inhibit upstream prostaglandin synthesis enzymes (PTGS1 and PTGS2), have minimal effects on hair growth because of likely equally decreased production of PGE2 and PGD2.
Given our current report that PGD2 inhibits hair growth, prosta- glandins represent an underappreciated network for controlling the rate of hair lengthening. Evidence to support the PGD2 pathway’s di- rect induction of the apoptotic catagen stage includes the temporal expression of Ptgds with catagen onset, in vitro studies of 15-dPGJ2 showing inhibition of hair growth, and the Ptgs2-overexpressing mouse model, which develops alopecia (23). These results are consistent with the notion that PTGDS elevation in balding scalp leads to increased levels of PGD2 and 15-dPGJ2, which then promote the onset of catagen and decrease hair lengthening, leading to the in- crease in telogen follicles and miniaturization of the hair follicle characteristic of AGA. PGD2 may also cause sebaceous hyperplasia seen in AGA.
Although we did not elicit premature catagen in mice treated topi- cally with PGD2, we observed a negative effect on hair growth (Fig. 6). This could be explained because of inappropriate prostaglandin delivery, frequency, or concentration. Other explanations include potential cofac- tors that are required with PGD2 to more directly affect hair cycling. Nevertheless, our results do suggest that prostaglandins directly modu- late speed of hair growth during anagen. Current explanations of the differences in hair length by species focus mostly on duration of hair follicle cycling rather than accompanying potential differences in hair- lengthening rates during anagen (4). Our results suggest that greater attention should be paid to the possibility that prostaglandins modulate hair growth speed and that compounds increasing hair growth speed may benefit patients with AGA.
Intriguingly, Ptgds is a highly testosterone-responsive transcript (30, 31), which further suggests its importance in AGA. PGD2 is thought to play a central role in male gonadal sex determination (32) and is highly expressed in male genitalia (32, 33). Similarly, Ptgds expression in the heart is regulated by estrogen (34). Estrogen leads to increases in 15-dPGJ2 levels in the uropygial gland (35). Recent evidence also suggests that pros- taglandins induce virilization of the mouse brain through estrogen (36). Given the androgens are aromatized into estrogens, these results may be relevant to hair growth and alopecia in both men and women. Thus, these or similar pathways might be conserved in the skin and suggest that sex hormone regulation of Ptgds may contribute to the pathogenesis of AGA.
Additional evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although min- oxidil alters potassium channel kinetics (7), it is also known to increase production of PGE2 (37). Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can con- comitantly decrease PGD2 levels and thus normalize multiple prosta- glandin species as a mechanism to improve AGA.
The lower absolute amount of 15-dPGJ2 compared to PGE2 and PGD2 is particularly relevant; although this eicosanoid has been hy- pothesized to be a natural ligand for the nuclear hormone transcription factor peroxisome proliferator–activated receptor g (PPARg), the measured concentration of 15-dPGJ2 is often lower than the binding constant for PPARg (17). Thus, although it is attractive to speculate that the sebaceous gland hypertrophy and elevated levels of 15-dPGJ2 ob- served in both human AGA and mouse K14-Ptgds model might be re- lated, the causal connection is unclear. Despite this, a growing literature correlates elevated 15-dPGJ2 levels with sebaceous hyperplasia, such as in acne (38). Given the common requirement of circulating sex hor- mones and common histology of sebaceous hyperplasia, acne and AGA may have overlapping pathogeneses.
Another report has linked altered lipid metabolism and alopecia (39). In a distinct type of human alopecia called lichen planopilaris, expression of PPARg is decreased with accompanying altered lipid metabolism. These were discovered through an approach similar to ours using micro- array analysis of affected and unaffected scalp. The most up-regulated transcript from affected subjects, cytochrome P450 family 1 member A1 (CYP1A1), was up-regulated 1020-fold. The authors hypothesized that a xenobiotic, such as dioxin, might up-regulate CYP1A1 expression and trigger lichen planopilaris. However, cytochrome P450s also have roles in eicosanoid biology, and they may alter prostaglandin metabolism (40). Thus, altered prostaglandin metabolism might contribute to more than one type of human alopecia, although additional studies are needed. Our findings should lead directly to new treatments for the most common cause of hair loss in men, AGA. Given its suspected role in allergic diseases, at least 10 antagonists of the GPR44 (DP-2) receptor have been identified (41) and several are in clinical trials (42). The potential for developing these compounds into topical formulations for treating AGA should elicit great interest moving forward. The ques- tion of whether similar changes in PGD2 levels are found in the affected scalp of women with AGA also needs to be addressed. AGA in women may not be androgen-mediated, but if prostaglandins represent a final common pathway, targeting prostaglandins should benefit women with AGA as well.
Our findings also suggest that supplemental PGE2 could be ther- apeutic. By correcting its deficiency and increasing its level in bald scalp, the inhibitory effects of PGD2 may be overcome. Analogs of PGF2a, which are already FDA-approved to promote eyelash growth, should also have similar effects on the scalp and are currently in clin- ical trials for this indication. Once issues of delivery, dosing, and safety are addressed, additional agonists and antagonists of prostaglandin pathways should become available. The K14-Ptgs2 transgenic mouse model, which phenocopies AGA, may assist in screening novel ther- apeutic agents. Ultimately, multiple mechanisms may be responsible for hair loss in AGA. Inhibiting PGD2 may prevent miniaturization and provide benefit to those in the process of balding; however, it is unclear whether men who are already bald will regrow hair.
Recent evidence has illustrated a role for prostaglandins in regulating hair growth. For example, the PGF2a analog latanoprost is Food and Drug Administration (FDA)–approved and routinely used clinically to enhance hair growth of human eyelashes (15). PGE2 has been pro- posed to protect from radiation-induced hair loss in mice (29), and both PGE2 and PGF2a have been shown to enhance hair growth in mice (20). Our studies show that prostaglandins are dysregulated in AGA, the most common type of hair loss in men. Specifically, PGD2 inhibits hair growth and thus represents a negative counterbalance to the pos- itive effects on hair growth shown for PGE2 and PGF2a.
There is precedence for the opposing functions of individual pros- taglandins that are downstream from the PTGS enzymes. For exam- ple, in the lung, PGE2 causes relaxation, whereas PGD2 causes contraction of bronchial muscle tone (16). Our results suggest that in mouse and human skin, a balance between PGE2 and PGD2 controls hair growth. This model predicts then that efforts to reverse alopecia should optimally focus on both enhancing PGE2 and inhibiting PGD2 signaling. This model also explains why agents such as aspirin, which inhibit upstream prostaglandin synthesis enzymes (PTGS1 and PTGS2), have minimal effects on hair growth because of likely equally decreased production of PGE2 and PGD2.
Given our current report that PGD2 inhibits hair growth, prosta- glandins represent an underappreciated network for controlling the rate of hair lengthening. Evidence to support the PGD2 pathway’s di- rect induction of the apoptotic catagen stage includes the temporal expression of Ptgds with catagen onset, in vitro studies of 15-dPGJ2 showing inhibition of hair growth, and the Ptgs2-overexpressing mouse model, which develops alopecia (23). These results are consistent with the notion that PTGDS elevation in balding scalp leads to increased levels of PGD2 and 15-dPGJ2, which then promote the onset of catagen and decrease hair lengthening, leading to the in- crease in telogen follicles and miniaturization of the hair follicle characteristic of AGA. PGD2 may also cause sebaceous hyperplasia seen in AGA.
Although we did not elicit premature catagen in mice treated topi- cally with PGD2, we observed a negative effect on hair growth (Fig. 6). This could be explained because of inappropriate prostaglandin delivery, frequency, or concentration. Other explanations include potential cofac- tors that are required with PGD2 to more directly affect hair cycling. Nevertheless, our results do suggest that prostaglandins directly modu- late speed of hair growth during anagen. Current explanations of the differences in hair length by species focus mostly on duration of hair follicle cycling rather than accompanying potential differences in hair- lengthening rates during anagen (4). Our results suggest that greater attention should be paid to the possibility that prostaglandins modulate hair growth speed and that compounds increasing hair growth speed may benefit patients with AGA.
Intriguingly, Ptgds is a highly testosterone-responsive transcript (30, 31), which further suggests its importance in AGA. PGD2 is thought to play a central role in male gonadal sex determination (32) and is highly expressed in male genitalia (32, 33). Similarly, Ptgds expression in the heart is regulated by estrogen (34). Estrogen leads to increases in 15-dPGJ2 levels in the uropygial gland (35). Recent evidence also suggests that pros- taglandins induce virilization of the mouse brain through estrogen (36). Given the androgens are aromatized into estrogens, these results may be relevant to hair growth and alopecia in both men and women. Thus, these or similar pathways might be conserved in the skin and suggest that sex hormone regulation of Ptgds may contribute to the pathogenesis of AGA.
Additional evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although min- oxidil alters potassium channel kinetics (7), it is also known to increase production of PGE2 (37). Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can con- comitantly decrease PGD2 levels and thus normalize multiple prosta- glandin species as a mechanism to improve AGA.
The lower absolute amount of 15-dPGJ2 compared to PGE2 and PGD2 is particularly relevant; although this eicosanoid has been hy- pothesized to be a natural ligand for the nuclear hormone transcription factor peroxisome proliferator–activated receptor g (PPARg), the measured concentration of 15-dPGJ2 is often lower than the binding constant for PPARg (17). Thus, although it is attractive to speculate that the sebaceous gland hypertrophy and elevated levels of 15-dPGJ2 ob- served in both human AGA and mouse K14-Ptgds model might be re- lated, the causal connection is unclear. Despite this, a growing literature correlates elevated 15-dPGJ2 levels with sebaceous hyperplasia, such as in acne (38). Given the common requirement of circulating sex hor- mones and common histology of sebaceous hyperplasia, acne and AGA may have overlapping pathogeneses.
Another report has linked altered lipid metabolism and alopecia (39). In a distinct type of human alopecia called lichen planopilaris, expression of PPARg is decreased with accompanying altered lipid metabolism. These were discovered through an approach similar to ours using micro- array analysis of affected and unaffected scalp. The most up-regulated transcript from affected subjects, cytochrome P450 family 1 member A1 (CYP1A1), was up-regulated 1020-fold. The authors hypothesized that a xenobiotic, such as dioxin, might up-regulate CYP1A1 expression and trigger lichen planopilaris. However, cytochrome P450s also have roles in eicosanoid biology, and they may alter prostaglandin metabolism (40). Thus, altered prostaglandin metabolism might contribute to more than one type of human alopecia, although additional studies are needed. Our findings should lead directly to new treatments for the most common cause of hair loss in men, AGA. Given its suspected role in allergic diseases, at least 10 antagonists of the GPR44 (DP-2) receptor have been identified (41) and several are in clinical trials (42). The potential for developing these compounds into topical formulations for treating AGA should elicit great interest moving forward. The ques- tion of whether similar changes in PGD2 levels are found in the affected scalp of women with AGA also needs to be addressed. AGA in women may not be androgen-mediated, but if prostaglandins represent a final common pathway, targeting prostaglandins should benefit women with AGA as well.
Our findings also suggest that supplemental PGE2 could be ther- apeutic. By correcting its deficiency and increasing its level in bald scalp, the inhibitory effects of PGD2 may be overcome. Analogs of PGF2a, which are already FDA-approved to promote eyelash growth, should also have similar effects on the scalp and are currently in clin- ical trials for this indication. Once issues of delivery, dosing, and safety are addressed, additional agonists and antagonists of prostaglandin pathways should become available. The K14-Ptgs2 transgenic mouse model, which phenocopies AGA, may assist in screening novel ther- apeutic agents. Ultimately, multiple mechanisms may be responsible for hair loss in AGA. Inhibiting PGD2 may prevent miniaturization and provide benefit to those in the process of balding; however, it is unclear whether men who are already bald will regrow hair.
Sì queste idroalcooliche sono a rischio nel senso che non dovrebbero esserci più sul mercato a meno che il provvedimento rientri.
Grande Julien che ha trovato lo studio integrale, dal quale con piacere vedo che si è ragionato in modo analogo al nostro, sull'inibizione generale delle PG che non sortirebbe effetti degni di nota sui capelli attenuando sia l'effetto positivo delle PGE2 che quello negativo delle PGD2.
Interessante apprendere questi vari collegamenti con altre patologie e con gli androgeni e pure ritornare sulla possibilità di usare analoghi del PGE2 per sovrastare gli effetti delle PGD2. Ci sarebbero poi in commercio già 10 antagonisti in del GPR44 e quindi il tutto sta a trovarli....[
]
Il sodio cromoglicato me lo ero tenuto come alternativa alla nigella, si tratta infatti di un famoso derivato dell'Amni Visnaga, ossia la kellina di cui qui avevamo già accennato in possibile funzione anti-aga.
Ne riparleremo.
Ciao
MA - r l i n
Grande Julien che ha trovato lo studio integrale, dal quale con piacere vedo che si è ragionato in modo analogo al nostro, sull'inibizione generale delle PG che non sortirebbe effetti degni di nota sui capelli attenuando sia l'effetto positivo delle PGE2 che quello negativo delle PGD2.
Interessante apprendere questi vari collegamenti con altre patologie e con gli androgeni e pure ritornare sulla possibilità di usare analoghi del PGE2 per sovrastare gli effetti delle PGD2. Ci sarebbero poi in commercio già 10 antagonisti in del GPR44 e quindi il tutto sta a trovarli....[
]Il sodio cromoglicato me lo ero tenuto come alternativa alla nigella, si tratta infatti di un famoso derivato dell'Amni Visnaga, ossia la kellina di cui qui avevamo già accennato in possibile funzione anti-aga.
Ne riparleremo.
Ciao
MA - r l i n
Prostaglandins are substances that have been involved in several physiological process, and in particular prostaglandin D2 has been involved in the endogenous sleep promotion, modulation of several central actions (regulation of body temperature, release of the luteinizing hormone), etc. Recently, it was shown that prostaglandin D (PGD) synthase binds retinoic acid and retinol. In addition, it was demonstrated that ALL-TRANS-RETINOIC ACID INHIBITS ITS ENZYMATIC ACTION but not retinol. With the generated information, it was suggested that retinoids may REGULATE THE SYNTHESIS OF PGD2, and that PGD synthase may be a transporter of retinoids to the place where they are required. Thus, it was suggested that PGD synthase plays a critical role in regulating the development of neurons by the regulation of the transfer of all-trans- or 9-cis-retinoic acid to RAR or RXR in the immature nerve cell.457 Additionally, it has been mentioned that the overexpression of the cyclooxygenase gene (a key enzyme in the forma- tion of prostaglandins) is an early and central event in colon carcinogenesis.
http://biblioteca.cinvestav.mx/indicadores/texto_completo/cinvestav/2000/162351_1.pdf
C'è sempre più roba che quadra. QUALCUNO Ricorda l'effetto positivo dell'inserimento dell'acido retinico nel minoxidil?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693596/
http://biblioteca.cinvestav.mx/indicadores/texto_completo/cinvestav/2000/162351_1.pdf
C'è sempre più roba che quadra. QUALCUNO Ricorda l'effetto positivo dell'inserimento dell'acido retinico nel minoxidil?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693596/
Quadra, ma non fa esultare....tanti hanno usato e usano tretinoina e non hanno avuto risultati così clamorosi, io stesso l'ho usata a lungo, ma mi aspettavo molto di più. Inoltre l'ho usata con la vit.D3 che è un altro ligando RXR, ma non ho visto ricrescita di miniaturizzati, solo capelli migliori, quelli sani.
Ciao
MA - r l i n
Ciao
MA - r l i n
in effetti vengono fuori parecchie evidenze. Quello che però sarebbe utile è capire quali di queste molecole hanno davvero ragione di essere usate in una cura per l'aga. Al momento io vedo solo il latanoprost che ha qualche dato e risultato dalla sua parte anche se nn sembra troppo selettivo. se il sodio cromoglicato possa essere utile potrebbe essere facilmente valutabile grazie ai colliri già esistenti (se il prezzo è abbordabile), magari testandolo su piccole zone.
collirio (10 ml al 4%) 9,40 €
http://www.torrinomedica.it/farmaci/schedetecniche/Lomudal_coll.asp
spray nasale (30 ml al 4%) 22,00 franchi svizzeri (circa 18 €)
http://www.torrinomedica.it/farmaci/schedetecniche/LOMUDAL_NASALE.asp
soluzione da nebulizzare (8,05 €)
http://www.sanihelp.it/farmaci/118.html
http://www.torrinomedica.it/farmaci/schedetecniche/Lomudal_coll.asp
spray nasale (30 ml al 4%) 22,00 franchi svizzeri (circa 18 €)
http://www.torrinomedica.it/farmaci/schedetecniche/LOMUDAL_NASALE.asp
soluzione da nebulizzare (8,05 €)
http://www.sanihelp.it/farmaci/118.html
io ho risolto il problema mal di testa da post tintura madre nigella, era un falso allarme fortunamente, e se la farmacia non resta senza vi saprò dire cosa succede!
Qualcun altro provi le altre sostanze se puo! ^^
Qualcun altro provi le altre sostanze se puo! ^^
io proverei il sodio cromoglicato ma vorrei partire in modo + razionale possibile avendo valutato tutti i pro e i contro.
Ecco i miei dubbi:
- da quel che leggo gli effetti collaterali per le patologie per cui è utilizzato sono blandi e rari con scarso assorbimento sistemico. non ci sono rischi (teorici ovviamente fino a controprova) di avere un maggiore assorbimento sitemico e maggiori sides?
- sembra che sia per l'asma che col collirio e spray nasale si richiedano dalle 3 alle 6 applicazioni al giorno. ciò mi fa pensare ad un'emivita molto bassa. secondo voi anche sui capelli bisogna apllicarlo così spesso?
- si può usare direttamento il collirio o lo spray nasale oppure bisogna farci preparare un'apposita lozione idroalcolica?
questi sono i dubbi che vengomo a me, se voi ne avete altri....
Ecco i miei dubbi:
- da quel che leggo gli effetti collaterali per le patologie per cui è utilizzato sono blandi e rari con scarso assorbimento sistemico. non ci sono rischi (teorici ovviamente fino a controprova) di avere un maggiore assorbimento sitemico e maggiori sides?
- sembra che sia per l'asma che col collirio e spray nasale si richiedano dalle 3 alle 6 applicazioni al giorno. ciò mi fa pensare ad un'emivita molto bassa. secondo voi anche sui capelli bisogna apllicarlo così spesso?
- si può usare direttamento il collirio o lo spray nasale oppure bisogna farci preparare un'apposita lozione idroalcolica?
questi sono i dubbi che vengomo a me, se voi ne avete altri....
il sodio è cmq un elemento e nn un farmaco di sintesi, questo insieme al fatto che viene usato topicamente deve tranquillizarti sul fatto che nn può avere un accumulo a livello sistemico, poi se ti vuoi scolare un litro al giorno nn saprei. []
Le applicazioni per l'asma sono frequenti perchè servono per evitare i sintomi ma l'emivita è un'altra cosa.
il collirio sicuramente è adatto, lo spray nasale o altre formulazioni nn saprei, ma farsi fare una lozione idroalcolica sarebbe la cosa migliore perchè la gradazione dell'alcol sarebbe quella ottimale.
]Le applicazioni per l'asma sono frequenti perchè servono per evitare i sintomi ma l'emivita è un'altra cosa.
il collirio sicuramente è adatto, lo spray nasale o altre formulazioni nn saprei, ma farsi fare una lozione idroalcolica sarebbe la cosa migliore perchè la gradazione dell'alcol sarebbe quella ottimale.
Per ora la caduta dei capelli al lavaggio é solo aumentata.. La cosa é da attribuire principalmente alla cessazione di fina da quasi un mese ormai e forse alla primavera. Di fatto la nigella sativa difficilmente parrebbe svolgere il ruolo della fina se alla fina attribuissimo proprietà indirette di inibizione della PGD2, perché dopo un pò di giorni con fina se avevo smesso da poco la caduta diminuisce subito.
Ora mi viene il dubbio che col fatto che la nigella inibisce anche la PGE2, non è che peggiora la situazione generale? Se continuo a osservare perdita al lavaggio sempre maggiore interromperò. Credo cmq che quest'ultima sia una ipotesi remota
Ora mi viene il dubbio che col fatto che la nigella inibisce anche la PGE2, non è che peggiora la situazione generale? Se continuo a osservare perdita al lavaggio sempre maggiore interromperò. Credo cmq che quest'ultima sia una ipotesi remota