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J Invest Dermatol 2001 Dec;117(6):1342-8
Steroid sulfatase in the human hair follicle concentrates in the dermal papilla.
5 alpha-dihydrotestosterone is known to play a crucial part in the regulation of hair growth and in the development of androgenetic alopecia. 5 alpha-dihydrotestosterone is formed locally within the hair follicle from the systemic precursor testosterone by cutaneous steroid 5 alpha-reductase. Moreover, adrenal steroids such as dehydroepiandrosterone are converted to 5 alpha-dihydrotestosterone by isolated hair follicles, which may provide an additional source of intrafollicular 5 alpha-dihydrotestosterone levels. Elevated urinary dehydroepiandrosterone and serum dehydroepiandrosterone sulfate have been reported to be present in balding young men. These reports suggest that dehydroepiandrosterone sulfate may act as an important endocrine factor in the development of androgenetic alopecia. Hence the question arises whether the dehydroepiandrosterone sulfate can be metabolized within the hair follicles to yield dehydroepiandrosterone by the microsomal enzyme steroid sulfatase, and where steroid sulfatase might be localized. We therefore performed immunostaining for steroid sulfatase on human scalp biopsies as well as analysis of steroid sulfatase enzyme activity in defined compartments of human beard and occipital hair follicles ex vivo. Using both methods steroid sulfatase was primarily detected in the dermal papilla. Steroid sulfatase activity was inhibited by estrone-3-O-sulfamate, a specific inhibitor of steroid sulfatase, in a concentration-dependent way. Furthermore, we show that dermal papillae are able to utilize dehydroepiandrosterone sulfate to produce 5 alpha-dihydrotestosterone, which lends further support to the hypothesis that dehydroepiandrosterone sulfate contributes to androgenetic alopecia and that steroid sulfatase inhibitors could be novel drugs to treat androgen-dependent disorders of the hair follicle such as androgenetic alopecia or hirsutism.
Ann Dermatol Venereol. 2003 Mar;130(3):326-30.
Intravenous pulse methylprednisolone therapy for severe alopecia areata: an open study of 66 patients
INTRODUCTION: Treatment of alopecia areata is a difficult challenge. Some European publications have shown encouraging results with high dose pulse corticosteroid therapy in extensive plurifocal alopecia areata. We undertook a prospective open study between January 2000 and December 2001 using repeated pulse each month, with the aim of identifying the effects of this repetition and underlining the best indications. PATIENTS AND METHODS: Sixty-six patients aged 9 to 60 years old presenting an extensive alopecia areata exceeding 30% of the scalp surface (n=47), alopecia totalis (n=8), alopecia universalis (n=8), ophiasic alopecia (n=3), for less than 12 months entered this study. The administered treatment was methylprednisolone 500 mg/d during 3 days or 5 mg/kg twice per day during 3 days in children. These pulses were repeated after 4 and 8 weeks, then a second series was carried out or not according to cases. The main evaluation criterion was the percentage of new terminal hair appearing on the bald areas, appreciated by clinical and photographic evaluation at 3 and 6 months. RESULTS: Ophiasic alopecia areata did not respond to treatment. A quarter of patients presenting universal alopecia had a good response (higher than 80 p. 100) followed by a relapse in half the cases. Half of the patients presenting alopecia totalis had a good response, which was maintained three times out of four. Multifocal alopecia areata seems the best indication since the patients under study presented a good response in 63.8 p. 100 of cases (78 p. 100 when it was a first episode and 90.5 p. 100 if the treatment had been started in less than 3 months before). The repetition of the pulses did not appear to increase the number of responders. CONCLUSION: This study provides the best indication of pulse methylprednisolone therapy: first recent episode of extensive plurifocal alopecia areata. These results are less convincing in long term history or other forms of alopecia areata.
Br J Nurs. 2003 May 8-21;12(9):550-8.
Case study of alopecia universalis and web-based news groups.
This article presents findings from an 18-month case study of a web-based news group used by individuals with alopecia universalis. Content analysis of 228 episodes of web-based communication that occurred in relation to themes of discussion was undertaken, supported by the use of concept mapping (Northcott, 1996). Analysis identified a core concept relating to that of a community of shared experience together with four supportive themes. The themes were the search for understanding and meaning, carrying on, seeking balance between past, present and future, and relating to new self, others, and the world. The article discusses the increased growth in the use of the web as a vehicle for exploring health concerns and the specific ethical and methodological issues raised by research in this area.
Hum Genet. 2003 Apr;112(4):400-3. Epub 2003 Feb 14.
Notch4, a non-HLA gene in the MHC is strongly associated with the most severe form of alopecia areata.
Alopecia areata (AA) is a disorder primarily affecting the hair and nails in which associated autoimmune or atopic disease is common. Genetically, it is a complex trait with evidence of a role for genes of the major histocompatibility complex (MHC), the interleukin-1 cluster and chromosome 21 in the pathogenesis. The strongest association is with HLA class II alleles, although whether this indicates a direct contribution to the pathogenesis or results merely from linkage disequilibrium with nearby disease genes is unknown. Notch4 is a recently defined gene in the HLA class III region. Notch signalling is a direct determinant of keratinocyte growth arrest and entry into differentiation. A possible role for Notch in hair growth has been indicated by transgenic mouse findings that activation of the Notch pathway in the hair cortex leads to aberrant differentiation of adjacent hair-shaft layers. Notch4 is therefore a plausible candidate gene for AA. We have examined two polymorphisms in the coding sequence of the Notch4 gene at positions +1297 and +3063 in a case-control study of 116 AA patients and 142 ethnically matched, healthy control subjects. The initial analysis showed a significant association of AA in the overall data set with the Notch4(T+1297C) polymorphism (P<0.001) but not with Notch4(A+3063G). To confirm this association, we genotyped an additional 62 patients and found that the risk for disease was higher in Notch4(+1297C) homozygotes [odds ratio (OR) 3.43 (1.63, 7.19)] than in heterozygotes [OR 2.58 (1.57, 4.24)]. On classifying the patients by severity of disease, the association appeared to be confined to the severest form (alopecia universalis) [OR 4.02 (1.64, 9.88), P=0.0014]. These results support previous findings showing that different HLA susceptibility alleles are associated with mild and severe AA.
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