harold
Established Member
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OK wanted to ask a question and again talk about inflammation maybe.
We all know that Nizoral/ketoconazole has some positive effects on hair. But we are not sure exactly why. it seems to be for a host of possible reasons - ketoconazole has been shown to reduce the activity of the androgen receptor/ DHT complex, it has been shown to enhance the growth of hair in mice, it is an antifungal (and also has anti-inflammatory and anti-bacterial properties), and it can interfere with steroid synthesis a lot earlier than the testosterone to dihydrotestosterone step. Which of these is important in giing it the effect of increasing hair density, diameter and reducing sebum output. It would seem obvious that it is the antiandrogenic properties that have this effect and the fact that it is also antifungal is purely coincidental.
However it is odd to consider that an unrelated antifungal - piroctine olamine performed at least as well as ketoconazole in terms of increasing hair density, diameter and reducing sebum output. Even "ordinary" antidandruff ingredient zinc pyrithione increased hair density though it did not help diamter or sebum output. It would seem to be something of a coincidence that PO is also antiandrogenic. Perhaps the fact that all these antifungal shampoos help to one extent or another is due to something else. A positive correlation has been found between telogen hair counts and dandruff severity in men suffering recurrent dandruff. People whose hair tested positive for the presence of Malassezia fungi was found far more often amongst "subjects with hair shedding than among normal subjects (89.92% vs 9.52%, p<0.001). Furthermore, participants with positive smears had a significantly higher frequency of hair loss complaints and positive hair-pull tests."
Amongst Korean adolescents suffering from androgenetic alopecia the disease most associated was sebborheic dermatitis, followed by acne and finally atopic dermatitis. Interesting that acne, considered the closest relative of Androgenetic Alopecia in the sense of its androgen dependece, was beaten out by seb derm and that atopic dermatitis - an inflammatory skin disease (with links to the same/similar type of fungus) came in next. The presence of Malassezia fungi has been shown to induce/alter cytokine production withim keratinocytes including our old friend TGF-Beta "Moreover, we demonstrated that M. furfur modulates proinflammatory and immunomodulatory cytokine synthesis by downregulating IL-1alpha and by inhibiting IL-6 and TNF-alpha and by upregulating IL-10 and TGF-beta1."
I find this....interesting. Its a whole bunch of circumstantial evidence but some of it at least seems to indicate that fungal infection/inflammatory aspects are very important. The fact that all antifungals - not just ketocconazzole - seem to help is the most difficult factor to explain.
If I were to take a shot - I would say that androgens lead to loss of immune privilege in vulnerable hair follicles as shown in the Cotsarelis patent and also sebaceous gland enlargement. An increased presence of lipophillic yeast triggers an immune response centred around the upper portions of the hair follicle as seen in pretty much all immunohistochemical investigations of male pattern baldness scalp. This being close to the "bulge" region of the follicle wherein the stem cell population that gives rise to future hair cycles lies - this is eventually caught in the crossfire, and, lacking sufficient markers to tell the immune system to "back off" is gradually destroyed.
I found this today from the 2005 article "Dermocosmetic Aspects of Hair and Scalp" by Trueb which had quite a few of these ideas.
"Clinical Approach to Common Hair and Scalp Complaints
Antonella Tosti reviewed conditions underlying common hair and scalp complaints, such as hair weathering, dandruff, itchy scalp, greasy scalp, and the "red scalp syndrome," and further characterized them on the basis of videodermoscopy findings. Epiluminiscence microscopy of the scalp at times 10 magnification reveals pathologic conditions of the hair shaft and scalp not readily recognized by the naked eye. Examples are hair diameter diversity, the "peripilar signs" (PPS) around the hair ostia and vascular abnormalities (teleangiectasia) of the scalp.
Hair diameter diversity has been identified as a marker for the hair follicle miniaturization process in the course of androgenetic alopecia (de Lacharrière et al, 2001).
A correlation of PSS with histological findings has revealed that the presence of PPS could reflect the presence of perifollicular inflammatory infiltrates and fibrosis (Deloche et al, 2004). The implication of microscopic follicular inflammation in the pathogenesis of androgenetic alopeica (Androgenetic Alopecia) has emerged from several independent studies (Jaworsky et al, 1992;Whiting, 1993;Mahéet al, 2000). The term "microinflammation" has been proposed, because the process involves a slow, subtle, and indolent course, in contrast to the inflammatory and destructive process in the classical inflammatory scarring alopecias (Mahéet al, 2000). An important question is how the inflammatory reaction pattern is generated around the individual hair follicle. The localization in the upper follicle near the infundibulum suggests that the primary causal event for the triggering of inflammation might occur at this site. Considering the microbial colonization of the follicular infundibulum, one could speculate that microbial toxins or antigens may be involved in the generation of the inflammatory response. Alternatively, keratinocytes themselves may respond to chemical stress from irritants, pollutants, and ultraviolet (UV) irradiation, by producing radical oxygen species, nitric oxide, and releasing pro-inflammatory cytokines. In the case where the causal agents persist, sustained inflammation occurs, together with connective tissue remodeling, where collagenases play a role. Collagenases are suspected to contribute to the tissue changes in perifollicular fibrosis. Finally, permanent hair loss results form irreversible damage to the putative site of follicular stem cells in the "bulge" area of the outer-root sheath in the superficial portion of the hair follicle (Lavker et al, 1993). The preference of this site for the immunologic attack may be related to the fact that, in contrast to the proximal hair follicle, the isthmus, and infundibulum area do not bear any immune privilege (Paus, 1997).
The "red scalp syndrome" is an ill-defined condition, characterized by persistent erythema of the scalp that is not otherwise explained through a specific dermatologic condition, such as seborrhoic dermatitis. First described byThestrup-Pedersen and Hjorth (1987), it has been commented upon in the English language byMoschella (1994), who stated the problem of "diffuse red scalp disease which can also be itchy and burning. Clinically, there is no scaling, no hair loss, and no scarring. It is non responsive to any therapy including potent topical steroids or anti-seborrhoic therapy." A study of 18 patients with "red scalp syndrome" showed that the scalp redness was associated with Androgenetic Alopecia in the majority of patients.1 Patients often report associated discomfort of the scalp (trichodynia). In another series of patients complaining of hair loss and trichodynia, the dermatoscopic finding of scalp telangiectasia was found to strongly correlate with the presence of trichodynia (Willimann and Trüeb, 2002). An interesting analogy to rosacea exists, in which it was found that patients with the telangiectatic variant respond more frequently with astinging sensation to the topical application of 5% lactic acid on the cheek than patients with the papulopustular type of rosacea or normal controls (Lonne-Rahm et al, 1999). In patients with trichodynia, overexpression of neuropeptide substance P has been found (Ericson et al, 1999), suggesting a connection between sensory or subjective irritation and cutaneous vascular reactivity."
Quick glossary - "trichodynia" basically means scalp pain and "telangiectasia" azre small dilated blood vessels close to the skin surface, the sort responsible for "port wine stain" birthmarks.
Substance P mediates stress related hair loss - "Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and beta2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege." Possibly it plays a role in male pattern baldness as well as it seems to be implicated in the red/painful/itchy nature of Androgenetic Alopecia scalp.
Thoughts people?
hh
We all know that Nizoral/ketoconazole has some positive effects on hair. But we are not sure exactly why. it seems to be for a host of possible reasons - ketoconazole has been shown to reduce the activity of the androgen receptor/ DHT complex, it has been shown to enhance the growth of hair in mice, it is an antifungal (and also has anti-inflammatory and anti-bacterial properties), and it can interfere with steroid synthesis a lot earlier than the testosterone to dihydrotestosterone step. Which of these is important in giing it the effect of increasing hair density, diameter and reducing sebum output. It would seem obvious that it is the antiandrogenic properties that have this effect and the fact that it is also antifungal is purely coincidental.
However it is odd to consider that an unrelated antifungal - piroctine olamine performed at least as well as ketoconazole in terms of increasing hair density, diameter and reducing sebum output. Even "ordinary" antidandruff ingredient zinc pyrithione increased hair density though it did not help diamter or sebum output. It would seem to be something of a coincidence that PO is also antiandrogenic. Perhaps the fact that all these antifungal shampoos help to one extent or another is due to something else. A positive correlation has been found between telogen hair counts and dandruff severity in men suffering recurrent dandruff. People whose hair tested positive for the presence of Malassezia fungi was found far more often amongst "subjects with hair shedding than among normal subjects (89.92% vs 9.52%, p<0.001). Furthermore, participants with positive smears had a significantly higher frequency of hair loss complaints and positive hair-pull tests."
Amongst Korean adolescents suffering from androgenetic alopecia the disease most associated was sebborheic dermatitis, followed by acne and finally atopic dermatitis. Interesting that acne, considered the closest relative of Androgenetic Alopecia in the sense of its androgen dependece, was beaten out by seb derm and that atopic dermatitis - an inflammatory skin disease (with links to the same/similar type of fungus) came in next. The presence of Malassezia fungi has been shown to induce/alter cytokine production withim keratinocytes including our old friend TGF-Beta "Moreover, we demonstrated that M. furfur modulates proinflammatory and immunomodulatory cytokine synthesis by downregulating IL-1alpha and by inhibiting IL-6 and TNF-alpha and by upregulating IL-10 and TGF-beta1."
I find this....interesting. Its a whole bunch of circumstantial evidence but some of it at least seems to indicate that fungal infection/inflammatory aspects are very important. The fact that all antifungals - not just ketocconazzole - seem to help is the most difficult factor to explain.
If I were to take a shot - I would say that androgens lead to loss of immune privilege in vulnerable hair follicles as shown in the Cotsarelis patent and also sebaceous gland enlargement. An increased presence of lipophillic yeast triggers an immune response centred around the upper portions of the hair follicle as seen in pretty much all immunohistochemical investigations of male pattern baldness scalp. This being close to the "bulge" region of the follicle wherein the stem cell population that gives rise to future hair cycles lies - this is eventually caught in the crossfire, and, lacking sufficient markers to tell the immune system to "back off" is gradually destroyed.
I found this today from the 2005 article "Dermocosmetic Aspects of Hair and Scalp" by Trueb which had quite a few of these ideas.
"Clinical Approach to Common Hair and Scalp Complaints
Antonella Tosti reviewed conditions underlying common hair and scalp complaints, such as hair weathering, dandruff, itchy scalp, greasy scalp, and the "red scalp syndrome," and further characterized them on the basis of videodermoscopy findings. Epiluminiscence microscopy of the scalp at times 10 magnification reveals pathologic conditions of the hair shaft and scalp not readily recognized by the naked eye. Examples are hair diameter diversity, the "peripilar signs" (PPS) around the hair ostia and vascular abnormalities (teleangiectasia) of the scalp.
Hair diameter diversity has been identified as a marker for the hair follicle miniaturization process in the course of androgenetic alopecia (de Lacharrière et al, 2001).
A correlation of PSS with histological findings has revealed that the presence of PPS could reflect the presence of perifollicular inflammatory infiltrates and fibrosis (Deloche et al, 2004). The implication of microscopic follicular inflammation in the pathogenesis of androgenetic alopeica (Androgenetic Alopecia) has emerged from several independent studies (Jaworsky et al, 1992;Whiting, 1993;Mahéet al, 2000). The term "microinflammation" has been proposed, because the process involves a slow, subtle, and indolent course, in contrast to the inflammatory and destructive process in the classical inflammatory scarring alopecias (Mahéet al, 2000). An important question is how the inflammatory reaction pattern is generated around the individual hair follicle. The localization in the upper follicle near the infundibulum suggests that the primary causal event for the triggering of inflammation might occur at this site. Considering the microbial colonization of the follicular infundibulum, one could speculate that microbial toxins or antigens may be involved in the generation of the inflammatory response. Alternatively, keratinocytes themselves may respond to chemical stress from irritants, pollutants, and ultraviolet (UV) irradiation, by producing radical oxygen species, nitric oxide, and releasing pro-inflammatory cytokines. In the case where the causal agents persist, sustained inflammation occurs, together with connective tissue remodeling, where collagenases play a role. Collagenases are suspected to contribute to the tissue changes in perifollicular fibrosis. Finally, permanent hair loss results form irreversible damage to the putative site of follicular stem cells in the "bulge" area of the outer-root sheath in the superficial portion of the hair follicle (Lavker et al, 1993). The preference of this site for the immunologic attack may be related to the fact that, in contrast to the proximal hair follicle, the isthmus, and infundibulum area do not bear any immune privilege (Paus, 1997).
The "red scalp syndrome" is an ill-defined condition, characterized by persistent erythema of the scalp that is not otherwise explained through a specific dermatologic condition, such as seborrhoic dermatitis. First described byThestrup-Pedersen and Hjorth (1987), it has been commented upon in the English language byMoschella (1994), who stated the problem of "diffuse red scalp disease which can also be itchy and burning. Clinically, there is no scaling, no hair loss, and no scarring. It is non responsive to any therapy including potent topical steroids or anti-seborrhoic therapy." A study of 18 patients with "red scalp syndrome" showed that the scalp redness was associated with Androgenetic Alopecia in the majority of patients.1 Patients often report associated discomfort of the scalp (trichodynia). In another series of patients complaining of hair loss and trichodynia, the dermatoscopic finding of scalp telangiectasia was found to strongly correlate with the presence of trichodynia (Willimann and Trüeb, 2002). An interesting analogy to rosacea exists, in which it was found that patients with the telangiectatic variant respond more frequently with astinging sensation to the topical application of 5% lactic acid on the cheek than patients with the papulopustular type of rosacea or normal controls (Lonne-Rahm et al, 1999). In patients with trichodynia, overexpression of neuropeptide substance P has been found (Ericson et al, 1999), suggesting a connection between sensory or subjective irritation and cutaneous vascular reactivity."
Quick glossary - "trichodynia" basically means scalp pain and "telangiectasia" azre small dilated blood vessels close to the skin surface, the sort responsible for "port wine stain" birthmarks.
Substance P mediates stress related hair loss - "Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and beta2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege." Possibly it plays a role in male pattern baldness as well as it seems to be implicated in the red/painful/itchy nature of Androgenetic Alopecia scalp.
Thoughts people?
hh
