alopecia
Metabolic and cellular analysis of alopecia in vitamin D receptor knockout mice.

Sakai Y, Kishimoto J, Demay MB.

Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Targeted ablation of the vitamin D receptor (VDR) results in hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, osteomalacia, and alopecia--the last a consequence of defective anagen initiation. To investigate whether the markedly elevated levels of 1,25-dihydroxyvitamin D led to the alopecia, we raised VDR-null mice in a ultraviolet light-free environment and fed them chow lacking vitamin D for five generations. Despite undetectable circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, alopecia persisted in the VDR-null mice, demonstrating that the alopecia was not secondary to toxic levels of 1,25-dihydroxyvitamin D interacting with an alternative receptor. Furthermore, alopecia was not seen in control littermates, suggesting that absence of ligand and absence of receptor cause different phenotypes. To identify the cell population responsible for the alopecia, we performed hair-reconstitution assays in nude mice and observed normal hair follicle morphogenesis, regardless of the VDR status of the keratinocytes and dermal papilla cells. However, follicles reconstituted with VDR-null keratinocytes demonstrated a defective response to anagen initiation. Hence, alopecia in the VDR-null mice is due to a defect in epithelial-mesenchymal communication that is required for normal hair cycling. Our results also identify the keratinocyte as the cell of origin of the defect and suggest that this form of alopecia is due to absence of ligand-independent receptor function.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11306599&dopt=Abstract alopecia, hair loss



alopecia
Strategies of coping and quality of life in women with alopecia.

Schmidt S, Fischer TW, Chren MM, Strauss BM, Elsner P.

Institute of Medical Psychology, University Hospital of the Friedrich Schiller University Jena, Stoystrasse 3, D-07740 Jena, Germany. silke.schmidt med.uni-jena.de

BACKGROUND: Measurements of the quality of life (QoL) have recently become an integral part of dermatological studies. Our hypothesis is that QoL in patients with certain diseases can be affected by strategies of coping behaviour, as well as by personality traits. OBJECTIVES: The aim of this study was to explore the particular correlation between QoL and strategies of coping in female patients with alopecia. PATIENTS: Fifty female patients, diagnosed with either diffuse or androgenetic alopecia, were evaluated by the use of Hairdex, an instrument developed to measure QoL in patients with hair loss. Most patients also underwent additional psychological assessments. RESULTS: Findings indicated that patients with highly visible hair loss reported a more negative impact on four Hairdex dimensions (functioning, emotions, self-confidence and stigmatization) than patients whose hair loss was only slightly visible. However, a subgroup of patients, with non-visible symptoms of hair loss, showed striking signs of psychological disturbance. These disturbed patients displayed either dysmorphophobic or affective disorder tendencies. CONCLUSIONS: Future studies using QoL as an instrument in research on patients with alopecia should consider that in cases of female alopecia these measurements may be affected by psychological disturbances.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11359394&dopt=Abstract alopecia, hair loss



alopecia
Androgen responsive genes as they affect hair growth.

Sawaya ME, Keane RW, Blume-Peytavi U, Mullins DL, Nusbaum BP, Whiting D, Nicholson DW.

ARATEC Research PO Box 7, Ocala, FL 34478, USA. Aratec worldnet.att.net

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11399535&dopt=Abstract alopecia, hair loss



alopecia
Early onset of androgenetic alopecia associated with early severe coronary heart disease: a population-based, case-control study.

Matilainen VA, Makinen PK, Keinanen-Kiukaanniemi SM.

Department of Public Health Science and General Practice, University of Oulu, Finland.

CONTEXT: The relationship of ischaemic heart disease (IHD) with androgenic alopecia (AGA) has been demonstrated, but no differentiation between early and late onsets of alopecia with regard to the risk and severity of IHD has been made. OBJECTIVE: To test if the early onset of alopecia is a risk factor for early severe, coronary artery disease (CAD) requiring surgery and to test if the early onset of AGA differs in this respect from the late onset of AGA. DESIGN: Population-based case-control study. SETTING AND PARTICIPANTS: All the 85 male persons living on 31 December 1999 in a Finnish town with total population of 7200, who had had a coronary revascularization procedure between March 1987 and January 1999, were drawn from the discharge register. For each case, an individually selected age-matched control person living in the same town was drawn from the official census register. MAIN OUTCOME MEASURE: Alopecia defined as grade 3 vertex or more on the alopecia classification scale of Hamilton, modified by Norwood South Med J, 68:1359-1365, 1975. RESULTS: The unadjusted odds ratio (OR) for coronary revascularization under the age of 60 years was 3.57 (95% confidence interval (CI) 1.19-10.72) in men with an early onset of AGA compared with men with normal hair status or late AGA. After multivariate adjustment for the traditional CAD risk factors, the corresponding OR was 3.18 (95% CI, 1.01-10.03). The unadjusted OR for the coronary revascularization procedure at any age was 2.14 (95% CI, 1.08-4.23) in the subgroup of the men with early AGA compared to those with late AGA or normal hair status. After adjustment for traditional risk factors this OR was 1.84, being nearly significant (95% CI, 0.90-3.77). CONCLUSION: Our results support the hypothesis that the early onset of AGA is a risk factor for an early onset of severe coronary heart disease.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11455846&dopt=Abstract alopecia, hair loss



alopecia
A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist.

Peters EM, Foitzik K, Paus R, Ray S, Holick MF.

Department of Medicine, Boston University Medical Center, MA 02118, USA.

Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11511291&dopt=Abstract alopecia, hair loss



alopecia
Association analysis of IL1A and IL1B variants in alopecia areata.

Tazi-Ahnini R, McDonagh AJ, Cox A, Messenger AG, Britton JE, Ward SJ, Bavik CO, Duff GW, Cork MJ.

Biomedical Genetics Project, Division of Genomic Medicine and Department of Dermatology, 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 disease is characterized by focal inflammatory lesions with perifollicular T-cell infiltrates, reflecting the role of local cytokine production in the development of patchy hair loss. IL-1 alpha and IL-1 beta are important inhibitors of hair growth in vitro. Their effect is opposed by the interleukin-1 receptor antagonist, IL-1ra. Genes of the IL-1 cluster are candidate genes in the pathogenesis of alopecia areata. To investigate the role of the IL-1 system in alopecia areata we examined three biallelic polymorphisms within the IL-1 gene cluster (IL1A+4845, IL1B+3954 and IL1B-511) in 165 patients and a large number of matched controls (n=1150). There was no significant association of IL1B-511 or IL1B+3954 genotypes with the overall dataset, or with disease severity or age at onset, in contrast with a previous report. The results suggested the possibility of an association with IL1A+4845 in the overall dataset [OR 1.39 (95% CI 1.00, 1.93)] although this was not statistically significant. This was due mainly to the contribution from mild cases of alopecia areata [OR 1.48 (0.96, 2.29)], suggesting that IL-1 alpha may have a particular role in the pathogenesis of this subgroup.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11703512&dopt=Abstract alopecia, hair loss