Ketoconazole shampoo: effect of long-term use in androgenic alopecia

BACKGROUND: The pathogenesis of androgenic alopecia is not fully understood. A microbial-driven inflammatory reaction abutting on the hair follicles might participate in the hair status anomaly. OBJECTIVE: The aim of our study was to determine if ketoconazole (KCZ) which is active against the scalp microflora and shows some intrinsic anti-inflammatory activity might improve alopecia. METHOD: The effect of 2% KCZ shampoo was compared to that of an unmedicated shampoo used in combination with or without 2% minoxidil therapy. RESULTS: Hair density and size and proportion of anagen follicles were improved almost similarly by both KCZ and minoxidil regimens. The sebum casual level appeared to be decreased by KCZ. CONCLUSION: Comparative data suggest that there may be a significant action of KCZ upon the course of androgenic alopecia and that Malassezia spp. may play a role in the inflammatory reaction. The clinical significance of the results awaits further controlled study in a larger group of subjects.     

Androgen regulation of the insulin-like growth factor-I and the estrogen receptor in rat uterus and liver

For the first time testosterone is shown to be an important regulator of the insulin-like growth factor-I (IGF-I) in the rat uterus under in vivo conditions. In this study the regulation of IGF-I and the estrogen receptor (ER) by gonadal steroids in the uterus and liver of female rats was monitored. The ER level was assayed by hormone binding after treatment with testosterone, 5 alpha-dihydrotestosterone or estradiol and specific mRNA species were analyzed by a solution hybridization/RNase protection assay using 35S-labeled RNA probes. Ovariectomized rats restored uterine weight after treatment with testosterone. Uterine IGF-I mRNA was more than 20-fold higher in testosterone treated rats compared to untreated ovariectomized controls after 48 h treatment. The effects of testosterone on ovariectomized animals was followed in a timecourse study. Testosterone administration increased uterine IGF-I mRNA expression during the first 48 h and the maximally induced level was maintained throughout the duration of the experiment (168 h). Since induction of IGF-I mRNA by estrogen is transient, these data indicate that androgen and estrogen increase IGF-I mRNA by different mechanisms. Regulation of IGF-I mRNA by gonadal steroids was also studied in hypophysectomized animals. The rats were given either testosterone, 5 alpha-dihydrotestosterone or estradiol, and uterine IGF-I mRNA was measured after 1 week of treatment. At this timepoint estrogen treated rats showed levels of IGF-I mRNA not significantly different from those of hypophysectomized controls. In contrast testosterone and 5 alpha-dihydrotestosterone increased the IGF-I mRNA level 30 and 40 times, respectively, relative to hypophysectomized control animals. Since 5 alpha-dihydrotestosterone is not convertable to estrogen, the induction by testosterone was considered to be a true androgenic phenomenon.     

Antibodies to hair follicles in alopecia areata

Although alopecia areata is suspected to be an autoimmune disease, no direct evidence of an altered immune response to components of the hair follicle has been reported. We studied whether antibodies to normal human anagen scalp hair follicles are present in individuals with alopecia areata. Thirty-nine alopecia areata sera and 27 control sera were tested by Western immunoblotting for antibodies to 6 M urea-extractable proteins of normal anagen scalp hair follicles. At serum diluted 1:80, all alopecia areata subjects (100%), but only 44% of control individuals, had antibodies directed to one or more antigens of approximately 57, 52, 50, 47, or 44 kD. The incidence of antibodies to individual hair follicle antigens in alopecia areata was up to seven times more frequent than in control sera and their level up to 13 times greater and was statistically significant for all five antigens. Tissue specificity analysis indicated that these antigens were selectively expressed in hair follicles. These findings indicate that individuals with alopecia areata have abnormal antibodies directed to hair follicle antigens, and support the hypothesis that alopecia areata is an autoimmune disease.     

Stimulation of CD40 in human bladder carcinoma cells inhibits anti-Fas/APO-1 (CD95)-induced apoptosis

Genetic predisposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as male pattern baldness. The involvement of the 5alpha-reductase enzyme in male pattern baldness has been postulated due to its role in the metabolism of testosterone to dihydrotestosterone. There are two known isozymes of 5alpha-reductase. Type I has been predominantly localized to the skin and scalp. Type II, also present on the scalp, is the target of finasteride, a promising treatment for male pattern baldness. We conducted genetic association studies of the 5alpha-reductase enzyme genes (SRD5A1 on chromosome 5 and SRD5A2 on chromosome 2) using dimorphic intragenic restriction fragment length polymorphisms. From a population survey of 828 healthy families comprising 3000 individuals, we identified 58 young bald men (aged 18-30 y) and 114 older nonbald men (aged 50-70 y) for a case control comparison. No significant differences were found between cases and controls in allele, genotype, or haplotype frequencies for restriction fragment length polymorphisms of either gene. These findings suggest that the genes encoding the two 5alpha-reductase isoenzymes are not associated with male pattern baldness. Finally, no clear inheritance pattern of male pattern baldness was observed. The relatively strong concordance for baldness between fathers and sons in this study was not consistent with a simple Mendelian autosomal dominant inheritance. A polygenic etiology should be considered.     

Intact hair follicle innervation is not essential for anagen induction and development

Neuropeptides produced, stored and secreted by the unusually dense sensory and autonomic innervation of hair follicles (HFs) can induce hair growth (anagen) and may be involved in hair growth control. To test the role of follicle innervation of HF cycling in vivo, we generated innervation-deficient HFs by unilateral surgical denervation of a defined region of back skin in C57BL/6 mice and assessed its effect on spontaneous and induced anagen development. Successful denervation was demonstrated by the absence of PGP 9.5+ or tyrosine hydroxylase+ nerves and nerve-associated neuropeptides (substance P, CGRP). By quantitative histomorphometry, no significant difference in spontaneous or cyclosporin A-induced anagen development could be detected between sham-operated control skin and denervated skin. Only after hair growth induction by depilation, a discrete, marginally significant retardation of anagen development was apparent in denervated HFs. Thus, even though cutaneous nerves may exert a minor modulatory role in depilation-induced hair growth, they are not essential for normal murine anagen development.     

Surveying the counselling needs of families with disablement in the United Arab Emirates

We have previously described spontaneous but reversible hair loss that clinically and histologically resembles human alopecia areata in a colony of C3H/HeJ mice. Alopecia areata in humans is associated with antibodies to hair follicles. This study was conducted to determine whether C3H/HeJ mice with hair loss have a similar abnormal antibody response to hair follicles. Eighteen C3H/HeJ mice with alopecia, 12 unaffected littermates, and 15 control mice were examined for circulating antibodies to C3H/HeJ anagen hair follicles by indirect immunofluorescence and against extracts of isolated C3H/HeJ and human anagen hair follicles by immunoblotting. Using both procedures, antibodies to anagen hair follicles were present in all C3H/HeJ mice with alopecia but in none of the control mice. The antibodies were also present in some unaffected C3H/HeJ littermates but were absent in mice of an unrelated strain with inflammatory skin disease and alopecia, indicating that their appearance did not result from the hair loss. These antibodies reacted to hair follicle-specific antigens of 40-60 kDa present in murine and human anagen hair follicles. These antigens were also reactive with human alopecia areata antibodies. Some of the antibodies in both C3H/HeJ mice and humans with alopecia areata reacted to antigens of 44 and 46 kDa, which were identified as hair follicle-specific keratins. This study indicates that C3H/HeJ mice with hair loss have circulating antibodies to hair follicles similar to those present in humans with alopecia areata. These findings confirm that these mice are an appropriate model for human alopecia areata and support the hypothesis that alopecia areata results from an abnormal autoimmune response to hair follicles.     

Hair cycle-dependent plasticity of skin and hair follicle innervation in normal murine skin

The innervation of normal, mature mammalian skin is widely thought to be constant. However, the extensive skin remodeling accompanying the transformation of hair follicles from resting stage through growth and regression back to resting (telogen-anagen-catagen-telogen) may also be associated with alteration of skin innervation. We, therefore, have investigated the innervation of the back skin of adolescent C57BL/6 mice at various stages of the depilation-induced hair cycle. By using antisera against neuronal (protein gene product 9.5 [PGP 9.5], neurofilament 150) and Schwann cell (S-100, myelin basic protein) markers, as well as against neural cell adhesion molecule (NCAM) and growth-associated protein-43 (GAP-43), we found a dramatic increase of single fibers within the dermis and subcutis during early anagen. This was paralleled by an increase in the number of anastomoses between the cutaneous nerve plexuses and by distinct changes in the nerve fiber supply of anagen vs. telogen hair follicles. The follicular isthmus, including the bulge, the seat of epithelial follicle stem cells, was found to be the most densely innervated skin area. Here, a defined subpopulation of nerve fibers increased in number during anagen and declined during catagen, accompanied by dynamic alterations in the expression of NCAM and GAP-43. Thus, our study provides evidence for a surprising degree of plasticity of murine skin innervation. Because hair cycle-associated tissue remodeling evidently is associated with tightly regulated sprouting and regression of nerve fibers, hair cycle-dependent alterations in murine skin and hair follicle innervation offer an intriguing model for studying the controlled rearrangement of neuronal networks in peripheral tissues under physiological conditions.     

Different populations of melanocytes are present in hair follicles and epidermis

Melanocytes in human skin reside both in the epidermis and in the matrix and outer root sheath of anagen hair follicles. Comparative study of melanocytes in these different locations has been difficult as hair follicle melanocytes could not be cultured . In this study we used a recently described method of growing hair follicle melanocytes to characterize and compare hair follicle and epidermal melanocytes in the scalp of the same individual. Three morphologically and antigenically distinct types of melanocytes were observed in primary culture. These included (1) moderately pigmented and polydendritic melanocytes derived from epidermis; (2) small, bipolar, amelanotic melanocytes; and (3) large, intensely pigmented melanocytes; the latter two were derived from hair follicles. The three sub-populations of cells all reacted with melanocyte-specific monoclonal antibody. Epidermal and amelanotic hair follicle melanocytes proliferated well in culture, whereas the intensely pigmented hair follicle melanocytes did not. Amelanotic hair follicle melanocytes differed from epidermal melanocytes in being less differentiated, and they expressed less mature melanosome antigens. In addition, hair follicle melanocytes expressed some antigens associated with alopecia areata, but not antigens associated with vitiligo, whereas the reverse was true for epidermal melanocytes. Thus antigenically different populations of melanocytes are present in epidermis and hair follicle. This could account for the preferential destruction of hair follicle melanocytes in alopecia areata and of epidermal melanocytes in vitiligo.     

Meeting the needs of gifted and talented preschoolers

The paper provides the evidence on interaction of the endocrine system hypophysis-gonads with varicocele. Gonadotropic hormones and sexual steroids were measured in the blood of varicocele males (47 cases) and of fertile healthy males (17 cases), testosterone in the tissue of the sexual glands and blood of white noninbred rats (40 test against 20 control animals). It was found that in 18% of varicocele patients high levels of FSH were associated with oligo-, pathospermia and changes in spermatogenic epithelium. Interstitial cell stimulating hormone did not shift above the standard in all varicocele patients, while testosterone was low in 15% of them and combined with hypogonadism manifestations. Progesterone rose high in 38% of the examinees. The discussion covers the problem of hyperprogesteronemia origin. Recommendations are given on gonadotropic hormones and sexual steroids assays which are thought useful in examination of the patients to validate pathogenetic treatment.     

Hair growth in neonatally undernourished rats

Interaction between neonatal undernutrition and the increased self-grooming activity upon hair growth of several body areas was analyzed in rats of 10, 20 and 30 days of age. Light microscopic observations on methylene blue impregnated hairs showed that these perinatal influences delayed the growth of hair follicles and thickness and length of hair measurements of the head and thoracic areas. The hair growth of lateral abdominal regions was less affected. Data suggest that hair alterations are primarily related to food deprivation since hair follicle measures of all skin areas were more affected than the distal hair measurements. Moreover, the distribution of impaired hair growth on different body areas correlates well with the increased self-grooming components associated to neonatal undernourishment.     

Induction of nest-material collecting in male Barbary doves by intracerebral androgen

The formation of androgen-binding protein (ABP) by cultured Sertoli cells, prepared from testes of immature rats, is increased when androgens or follicle-stimulating hormone (FSH) are present in the medium. Testosterone and 5alpha-dihydrotestosterone are equally effective in stimulating the synthesis and secretion of ABP, but non-androgenic steroids examined (progesterone, 17beta-estradiol and corticosterone) are without influence. Maximal increases are observed when androgens are added at the time of cell plating. Cells maintained in culture medium devoid of hormones become progressively less sensitive to subsequent addition of testosterone or FSH. Data are discussed in relation to the sites of androgen requirements for spermatogenesis.     

A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice

Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia on to female nude mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned nude mice. We used this recently reported model to study the effect of a new non-steroidal antiandrogen-RU58841-on human hair growth. Twenty productive scalp grafts from balding men were maintained for 8 months after grafting on to nude mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 300 micrograms in 10 microL; 5 days/week) on the non-grafted flank. The scalp samples were divided equally according to the estimated hair production potential, which was based on the amount of hair present on the scalp samples before grafting. Each of the two equal groups of grafts was further allocated at random to be treated topically (5 days/week) with blinded solutions of either RU58841 1% in ethanol, or ethanol as a control. Twenty-eight active follicles appeared on the 10 control grafts. Among them only two follicles (7%) initiated a second hair cycle. However, the 10 RU58841-treated grafts bore a total of 29 active follicles, and eight of them (28%) showed a second cycle. The values for the linear hair growth rates (LHGR) were significantly (P < 0.04) higher in the RU58841-treated group. Recycling and increased LHGR indicate a positive action for RU58841 on human hair growth from balding samples grafted on to testosterone-conditioned nude mice, and encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia.     

Follicular bisection in hair transplantation surgery: an in vitro model

The aim of this study was to evaluate, in an in vitro model, the survival and growth rates of transversely sectioned human hair follicles to assess experimentally the soundness of this approach as a future possible method for "duplicating" available donor hair grafts in hair transplantation procedures. A total of 300 human anagen hair follicles was obtained from 10 healthy male patients. Follicles were thus randomly assigned to one of the following groups: group A (control; n = 100 follicles), cultured intact as dissected, and group B (experimental; n = 200 follicles), transversely transected, parallel to the epidermal surface and immediately below the bulge area, to obtain 200 lower-half follicles and 200 upper-half follicles. Isolated hair follicles from both groups were maintained in culture for 10 days. The length of each follicle was measured immediately following isolation and at the end of the 10-day culture period. No statistically significant differences were found between the growth rate of intact follicles (mean 10-day growth rate = 2.71 mm) and of lower-half follicles (mean 10-day growth-rate = 2.64 mm), whereas a statistically significant difference was found between the growth rate of follicles from the two above-mentioned groups and the growth rate of the "upper-half" follicles (mean 10-day growth rate = 1.07 mm). Histologic analysis demonstrated that both intact and lower-half follicles maintained a normal histologic appearance, whereas in upper-half follicle sections we invariably detected a region of intense cell proliferation, reminiscent of a regenerated follicular papilla, surrounding the lowermost part of the follicle. In our opinion, the reported in vitro survival rate of transected human hair follicles might represent an interesting starting point in striving to augment the number of donor hairs available during a hair transplantation procedure.     

Loose anagen syndrome and loose anagen hair

Loose anagen syndrome, or loose anagen hair, is a recently described condition of unknown etiology that may be under-recognized. The typical patient is a child with sparse fine hair that can easily be pulled out. The diagnosis is confirmed by microscopic examination of firmly pulled hairs, many of which are in the anagen phase but lacking an inner and outer root sheath and demonstrating a ruffled cuticle. Some presentations of alopecia areata may be confused with this condition, but the pull test analysis serves to differentiate them. A variety of theories have been postulated to explain the pathophysiology of loose anagen syndrome. In some cases, there is an autosomal dominant pattern of inheritance. In most cases, this condition spontaneously improves with age.     

Long-term epilation using the EpiLight broad band, intense pulsed light hair removal system

BACKGROUND: The long-term epilation of hair is the goal of several lasers and intense pulsed light systems. OBJECTIVE: The purpose of the study is to use the EpiLight Hair Removal System to assess long-term epilation and to assess its safety profile following a single treatment session. METHODS: Patients received a single treatment with the Epilight Hair Removal System after entering the patient's skin type, skin color, hair color, and hair density into the system's computer software. Treatment parameters include various wavelengths of light, pulse duration, pulse delay, and energy fluence. Thirty-seven subjects received a single treatment using one of four cut-off filters consisting of two to five pulses with energies of 34-55 J/cm2. RESULTS: The results of a single treatment show hair clearances occurring immediately and over a 12-week study period. Approximately 60% hair removal was noted at 12 weeks. CONCLUSIONS: The EpiLight Hair Removal System is an effective and safe method for long-term epilation of unwanted hair.     

Chronic telogen effluvium

Chronic telogen effluvium is not uncommon. It is a form of diffuse hair loss affecting the entire scalp for which no obvious cause can be found. It usually affects women of 30 to 60 years of age who generally have a full head of hair prior to the onset of shedding. The onset is usually abrupt, with or without a recognizable initiating factor. The degree of shedding is usually severe in the early stages and the hair may come out in handfuls. Chronic telogen effluvium has distinctive clinical and histologic features that are usually diagnostic. Chronic telogen effluvium contrasts with classic acute telogen effluvium by its persistence and its tendency to fluctuate for a period of years. Patients are particularly troubled by the continuing hair loss and fear total baldness. Repeated reassurance that the condition represents shedding rather than actual hair loss and does not cause complete baldness is necessary. Chronic telogen effluvium does appear to be self-limiting in the long run.     

Histology and cytochemistry of human skin. XXXVI. The nose and lips

The skin of the nose is characterized by often conspicuously dilated openings of the ducts of many subaceous follicles. Histological sections are dominated by gigantic sebaceous follicles, but there are also numerous vellus hairs with small sebaceous glands. All hair follicles on the surface of the nose and in the vestibule are completely invested with nerve end organs. In the vestibule, the glabrous upper surface has intraepidermal nerves and a few mucocutaneous end organs. the vermillion zone of the lip, which seperates the skin of the external lip and the mucosa of the inner lip, is keratinizing glabrous epithelium, often with numerous sebaceous glands in the upperlip. The transitional area between the keratinizing epithelium of the vermillion and the nonkeratinizing epithelium of the labial mucosa is abundantly supplied with mucocutaneous end organs, with only a few in the labial mucosa. The mucoserous glands of the labial mucosa are richly innervated.     

Changing patterns of cell adhesion molecules during mouse pelage hair follicle development. 2. Follicle morphogenesis in the hair mutants, Tabby and downy

Wild-type mice have three main types of hair in their pelage: tylotrichs, awls and zigzags. Tabby mice have a yellowish coat consisting of awls only, whereas downy mice have a sparse grayish coat consisting of unusually fine hairs. The spatial and temporal distribution of cell adhesion molecules (CAMs) during hair follicle morphogenesis was investigated in the mutants and compared with that in nonmutant mice. In Tabby embryos, awl follicles developed normally and showed normal immunostaining patterns for E-cadherin, P-cadherin and N-CAM. Prior to follicle initiation, however, some deviations from normal skin morphology and staining patterns indicated a delay in the development of the basal epidermal layer. On the other hand, the stratum corneum was formed prematurely. Therefore, the lack of tylotrich and zigzag follicles in Tabby mice might be explained by a general defect in epidermal development rather than by abnormal CAM expression. In downy embryos, tylotrich and awl follicles were initiated within the normal time periods, but elongation and differentiation of most follicles were abnormal. At birth, most follicles were small and/or severely deformed but showed normal CAM expression patterns. Extreme distortion and disorientation of follicles seemed to be associated with disintegration of the dermal papilla and abnormal mesenchymal cell condensations between the follicles. This suggests that abnormal hair development in downy mice might result from a defect in dermal rather than epidermal components of the skin.