alopecia
Targeting expression of the human vitamin D receptor to the keratinocytes of vitamin D receptor null mice prevents alopecia.

Chen CH, Sakai Y, Demay MB.

Endocrine Unit, Massachussetts General Hospital and Harvard Medical School, Boston MA. USA.

Vitamin D receptor (VDR) null mice develop hypocalcemia, hyperparathyroidism, rickets, osteomalacia and alopecia. Normalization of mineral ion homeostasis prevents all of these abnormalities except alopecia. Hair reconstitution assays, performed in athymic nude mice, demonstrate that the lack of VDR in keratinocytes leads to a defect in anagen initiation, similar to that observed in VDR null mice. Although these studies demonstrate that expression of the VDR in keratinocytes is necessary, they do not prove that it is sufficient for maintenance of the normal hair cycle. To address this hypothesis, we generated transgenic mice expressing the human VDR under the control of the keratin 14 (K14) promoter. Two highly expressing transgenic lines were mated with VDR null mice to obtain VDR null mice expressing the human VDR transgene (hVDR+/mVDR-). Expression of the transgene in the VDR null mice prevented alopecia. Furthermore, when subjected to anagen initiation, the hair follicle keratinocytes of the hVDR+/mVDR- mice demonstrated an enhanced proliferative response compared to those of control littermates. Restoration of VDR expression in the keratinocytes of VDR null mice, prevents the hair cycle defect that leads to the development of alopecia.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11713240&dopt=Abstract alopecia, hair loss



alopecia
Galea fixation in alopecia reduction surgery.

Seery GE.

Hair Transplantation Clinic of Sacramento, Sacramento, California, USA. geseery home.com

BACKGROUND: Alopecia reduction surgery, because of a high incidence of complications, has become a seldom used operation. OBJECTIVE: To show that galea fixation alopecia removal/scalp reduction is simple, safe, highly effective, and largely complication-free. METHODS: Conclusions derived are based on studies of more than 1000 alopecia removal operations, done personally, including 700 performed as part of a surgical research project with specific protocols and goals. CONCLUSIONS: Effective, safe alopecia reduction surgery is possible when incision patterns do not transect either neurovascular structures or collagen and undermining is judicious. Deep plan fixation is regarded as critical to an optimal result.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11737126&dopt=Abstract alopecia, hair loss



alopecia
Effect of adenovirus-mediated expression of Sonic hedgehog gene on hair regrowth in mice with chemotherapy-induced alopecia.

Sato N, Leopold PL, Crystal RG.

Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.

BACKGROUND: The Sonic hedgehog (Shh) gene is involved in the initiation of hair growth. We have shown that localized, transient, enhanced expression of the Shh gene in mouse skin mediated by an adenovirus (AdShh) vector accelerates initiation of the anagen (i.e., growth) phase of hair follicle development. Because hair regrowth in chemotherapy-induced alopecia is associated with follicle cell proliferation and active melanogenesis similar to that observed in the anagen phase of normal hair growth, we examined whether AdShh-mediated Shh expression would accelerate hair regrowth in the skin of mice with chemotherapy-induced alopecia. METHODS: After establishment of cyclophosphamide-induced alopecia, in either 3- or 7-week-old mice, AdShh or a control vector (AdNull) was delivered to dorsal skin by intradermal injection. Hair regrowth and melanogenesis were assessed by histology and gross morphology. Fisher's exact test was used to compare differences in outcomes between AdShh-treated and control (AdNull-treated or not injected with any vector [naive]) mice. All statistical tests were two-sided. RESULTS: Northern blot analysis confirmed enhanced Shh expression after AdShh administration in 7-week-old mice. Two weeks after AdShh administration, the injection site (all of five mice) showed large, anagen-phase hair follicles with a normal distribution of melanin. In contrast, both skin treated with AdNull (all of five mice) and skin from naive mice (all of five mice) showed dystrophic hair follicles with irregular distribution of melanin (P<.001 in both comparisons). Gross morphologic observations confirmed that AdShh-treated mice, but not naive mice or AdNull-treated mice, showed skin darkening at the injection site indicative of entry into anagen phase (P<.001 in both comparisons). AdShh treatment of 3-week-old mice with cyclophosphamide-induced alopecia was followed by accelerated hair follicle recovery (19 of 22 mice); such recovery was not observed at this rate in AdNull-treated or naive skin (P<.001 for both comparisons). CONCLUSION: Localized, transient, enhanced expression of Shh gene in skin, mediated by an adenovirus vector, might be a future strategy to accelerate hair follicle regrowth after chemotherapy-induced alopecia.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11752010&dopt=Abstract alopecia, hair loss



alopecia
Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction.

Tazi-Ahnini R, Cox A, McDonagh AJ, Nicklin MJ, di Giovine FS, Timms JM, Messenger AG, Dimitropoulou P, Duff GW, Cork MJ.

Division of Genomic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. r.taziahnini sheffield.ac.uk

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11841485&dopt=Abstract alopecia, hair loss



alopecia
Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.

Barahamani N, de Andrade M, Slusser J, Zhang Q, Duvic M.

Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11841553&dopt=Abstract alopecia, hair loss