Sistemicamente perché può dare problemi anche seri sopratutto se usato alla lunga e topicamente perché pare comunque un inibitore generico delle prostaglandine e quindi non mirato alle sole PGD2.
Spulciando poi il sacro testo di Garza[
] faccio notare questi passaggi cruciali:
The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp (scalpo è quanto di più vasto si possa intendere in tricologia....)
We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. (applicando le PGD2 topicamente, a mo' di lozione, si ha inibizione della crescita dei peli dei topi....quindi nulla di particolarmente posizionato in alcune cellule e non in altre...)
...tutto questo nel solo abstract....
We discovered a significant increase in PGD2 in the balding scalp compared to haired scalp by immunoassay (Fig. 2D). The absolute level of PGD2 was 16.3 ng/g tissue in balding scalp and 1.5 ng/g tissue in haired scalp. (ancora lo scalpo...non cellule particolari...).
Passando all'analisi dei cheratinociti:
In hair follicles undergoing catagen, PTGDS was present in mast cells within the fibrous streamer, which is the former site of the regressed follicle (Fig. 4E). These results in mouse and human demonstrate that the lipocalin PTGDS and its product PGD2 are predominantly expressed in the transient portion of the follicle at a time when the follicle begins regressing. These findings are in line with our hypothesis. (pare proprio che i mastociti - mast cells - cacciati dalla porta rientrino dalla finestra[
])
To test the effect of PGD2 on human hair growth, we used explanted human hair follicles maintained in culture for 7 days. We added increasing amounts (from 0 to 10 mM) of PGD2, 15-dPGJ2, or vehicle to the culture medium and measured hair length (Fig. 6D). Starting at 5 mM, PGD2 and 15-dPGJ2 significantly inhibited hair growth. At 10 mM, PGD2-treated hair was 62 ± 5%shorter than vehicle, whereas 10 mM 15-dPGJ2 completely inhibited all hair growth. (quindi per bloccare la crescita del capello hanno usato le prostaglandine e pertanto abbassando le stesse dovrebbe sortire l'effetto opposto...).
Our results suggest thatin 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 (qui ipotizzano che gli inibitori generici delle prostaglandine non avrebbero effetto sull'aga perché non specifici per le PGD2...)
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 increase in telogen follicles and miniaturization of the hair follicle characteristic of AGA. PGD2 may also cause sebaceous hyperplasia seen in AGA.(quindi le PGD2 sono un po' dappertutto sullo scalpo e sono nocive nel complesso coinvolgendo anche la ghiandola sebacea, come è noto a tutti gli agati...).
Ma a favore di un'azione di riduzione delle PGD2 ci sarebbe anche questo documento:
http://southernresearchco.com/pgd2-inhibitors
Pathways of Prostaglandin D2 Inhibitors
Prostaglandin D2 inhibition can occur through three primary pathways. The most potent mechanism of prostaglandin D2 inhibition, not surprisingly, is inhibition or antagonism at the receptor level.
Inhibition can occur through prevention of receptor expression via inhibition of signal transduction, competitive inhibition (preventing the binding of agonists and thus reducing or preventing their effect according to potency of the inhibitor), or antagonism (defined as competitive inhibition with inverse or opposite effects compared to agonists, and measured in proportion to the opposite effect exerted). Other mechanisms, such as disruption of phosphorylation of the receptor, are also possible. Some analogs of other prostaglandins, such as prostaglandin F2a, have exhibited antagonistic effects on PGD2 receptor subtypes. In addition to allosteric inhibition by PGF2a, positive allosteric effects from 15deoxyPGJ2 derived from PGD2 may occur at the GPR44 receptor.
The Prostaglandin D2 synthase (PTGDS) is an enzyme that converts AA/PGH2 into prostaglandin D2, typically very close to target tissues and acting in a paracrine fashion. Total PTGDS inhibition is not a likely mechanism to treat AA due to the temporary nature of reduction in PTGDS , and the lack of upstream and downstream control: availability of arachidonic acid and PGD2 receptors (in particular the CRTH2-GPR44 receptor) is likely to create more PTGDS and overcome the potential therapeutic effect.
A final PGD2 inhibition pathway is mast cell stabilization, which prevents release of prostaglandin D2 and thus prevents it from reaching target tissues. Regardless of synthesis of PGD2 or receptor availability, prevention of prostaglandin D2 release is an effective method of PGD2 inhibition. Mast cell stabilizers are safe and effective for use in humans, and may be a part of future formulations for PGD2 inhibition.
Ciao
MA - r l i n
