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Dynamic ultrastructural changes of the connective tissue sheath of human hair follicles during hair cycle.

Ultrastructural changes of the connective tissue sheath (CTS), including the hyaline membrane, of human hair follicles during the hair cycle, were studied in normal scalp skin specimens. In early anagen, the CTS was composed of a thin basal lamina and surrounding collagen tissue. The collagen tissue gradually thickened during the development of the hair and hair follicle. In mature anagen hair follicles, the collagen tissue was separated into three layers. The inner collagen layer, just outside the basal lamina, was thin and composed of collagen fibres running longitudinally parallel to the hair axis. The middle collagen layer was very thick with its collagen fibres running transversely against the hair axis and surrounding the inner hair tissue. Many fibroblasts were present among the collagen fibres in the middle layer, whereas the inner layer contained almost none. In the outer collagen layer, collagen fibres ran in various directions parallel to the outer surface of the outer root sheath cells. In late anagen, the basal lamina became very thick. In catagen, the basal lamine and the inner collagen layer became corrugated and showed oedematous change and degeneration. Surrounding fibroblasts showed active production of new collagen fibres, which seemed to fill the spaces left by the retraction of the hair follicle and hyaline membrane. These ultrastructural changes of the CTS show that there may be dynamic metabolic changes of the connective tissue around human hair follicles during the hair cycle.

Adolescent↗

Effects of immunosuppressive peptidyl-prolyl cis-trans isomerase (PPIase) inhibitors, cyclosporin A, FK506, ascomycin and rapamycin, on hair growth initiation in mouse: immunosuppression is not required for new hair growth.

The effects of immunosuppressive peptidyl-prolyl cis-trans isomerase (PPIase) inhibitors, cyclosporin A, FK506, ascomycin and rapamycin, on hair growth initiation (anagen hair induction) in mouse were studied by topical application on the dorsal skin surface during the telogen phase of the hair cycle. Single applications of cyclosporin A and FK506 (10 to 100 nmol in 5 microliters of ethanol) induced new hair growth in 12 days within the restricted area where the compounds were applied. On the other hand, ascomycin and rapamycin did not initiate new anagen hairs even at higher doses (1 mumol in 5 to 10 microliters of ethanol). The effects of simultaneous application of the immunosuppressants were also tested by a single topical application. Ascomycin did not inhibit the anagen hair induction by cyclosporin A, but inhibited hair induction by FK506. Rapamycin inhibited new hair growth induced by cyclosporin A and FK506. These results suggest that the inhibition of PPIase is not required for the initiation of a new hair cycle in mice, and that anagen hair induction caused by cyclosporin A and FK506 is not a result of immunosuppression. The present results also indicate that a single application of an adequate quantity of cyclosporin A and FK506 is sufficient to initiate new hair growth.

Administration, Topical↗

Hair bundles of sea anemones as a model system for vertebrate hair bundles.

Sea anemones are marine invertebrates that use hair bundles to detect swimming movements of prey. Prey are captured by nematocysts (stinging capsules) that discharge into the prey. To further characterize anemone hair bundles and to compare hair bundles in anemones with hair bundles in vertebrates, we investigated fine structure and cytochemistry of anemone hair bundles. In addition, using a biological assay based on counting nematocysts discharged into vibrating test probes, we examined sensitivity of vibration detection to aminoglycoside antibiotics, Ca(2+)-free seawater, and amiloride. Like vertebrate hair bundles, anemone hair bundles are composed of stereocilia, possess lateral linkages between stereocilia whose preservation for transmission electron microscopy is enhanced by ruthenium red, and possess tip links morphologically similar to vertebrate tip links. Furthermore, vibration-dependent discharge of nematocysts is reversibly inhibited by 10(-4) M streptomycin and abolished by brief exposure to Ca(2+)-free seawater. However, unlike vertebrate hair bundles, anemone hair bundles appear to be insensitive to amiloride since vibration-dependent discharge of nematocysts is unaffected by up to mM amiloride. Thus, anemone hair bundles may serve as a useful model system for vertebrate hair bundles with the interesting feature of being insensitive to amiloride.

Amiloride↗

Cyclosporin a promotes hair epithelial cell proliferation and modulates protein kinase C expression and translocation in hair epithelial cells.

Cyclosporin A is an immunosuppressive agent known to cause hirsutism. The mechanisms of action that cause hirsutism have not been fully elucidated, however. We have previously reported that several selective protein kinase C inhibitors promote the growth of murine hair epithelial cells and stimulate anagen induction. In this paper, we report on an investigation of the mechanisms of action of hair-growing activity possessed by cyclosporin A from the viewpoint of whether it promotes hair epithelial cell growth or whether it modulates the expression or translocation of protein kinase C isozymes in hair epithelial cells. Our results indicate that cyclosporin A (over a wide dosage range of 1-1000 ng per ml) stimulates cultured murine hair epithelial cell growth to about 150%-160% relative to controls. We also observed growth-promoting effects on murine epidermal keratinocytes (about 140%) at the dose range of 1-100 ng per ml. At high dose ranges above 3 microg per ml, the growth of both cells was inhibited. On the other hand, we found that cyclosporin A reduces the overall expression of protein kinase C alpha, betaI, and betaII in cultured murine hair epithelial cells, and reduces the levels of protein kinase C alpha, betaI, betaII, and eta in the particulate fraction from cultured murine hair epithelial cells. From these results, we speculate that the hair-growing activity of cyclosporin A is at least partially attributable to its growth-promoting influence on hair epithelial cells sequential to its downregulation of some protein kinase C isozymes in hair epithelial cells or inhibition of translocation of some protein kinase C isozymes to the membrane or cytoskeleton of hair epithelial cells.

Animals↗

Phosphatidic acid has a potential to promote hair growth in vitro and in vivo, and activates mitogen-activated protein kinase/extracellular signal-regulated kinase kinase in hair epithelial cells.

Phospholipids have recently been discovered to play an important role in cellular regulation. In this study, we focused on phosphatidic acid and lysophosphatidic acid, which are phospholipids known to possess growth-hormonal effects on several types of cells, and examined their growth-promoting effects on murine hair epithelial cells. We discovered that phosphatidic acid possesses intensive growth-promotional effects on hair epithelial cells and epidermal keratinocytes. In contrast, lyso-phosphatidic acid showed lower growth-promoting effects on hair epithelial cells relative to phosphatidic acid and showed minimal or no growth-promoting activity on epidermal keratinocytes. Phosphatidic acid was also shown to have hair-growing activity to induce the anagen phase of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of phosphatidic acid, we examined its relationship to the mitogen-activated protein kinase cascade linked to cell proliferation and the transforming growth factor beta signal pathway known to be a regulator of catagen induction. We confirmed that phosphatidic acid activates MEK-1/2 and upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. Addition of transforming growth factor beta1 to hair epithelial cell cultures concentration-dependently decreased cell growth and induced apoptosis; however, addition of phosphatidic acid to the culture neutralized the growth-inhibiting effects of transforming growth factor beta1 and protected the cells from apoptosis. We speculate that the hair-growing activity of phosphatidic acid is at least linked to its growth-promoting effects on hair epithelial cells that follow mitogen-activated protein kinase/extracellular signal-regulated kinase kinase activation and its protective action on transforming-growth-factor-beta1-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.

Animals↗

Androgen regulation of the human hair follicle: the type I hair keratin hHa7 is a direct target gene in trichocytes.

Previous work had shown that most members of the complex human hair keratin family were expressed in terminal scalp hairs. An exception to this rule was the type I hair keratin hHa7, which was only detected in some but not all vellus hairs of the human scalp (Langbein et al, 1999). Here we show that hHa7 exhibits constitutive expression in medullary cells of all types of male and female sexual hairs. Medullated beard, axillary, and pubic hairs arise during puberty from small, unmedullated vellus hairs under the influence of circulating androgens. This suggested an androgen-controlled expression of the hHa7 gene. Further evidence for this assumption was provided by the demonstration of androgen receptor (AR) expression in the nuclei of medullary cells of beard hairs. Moreover, homology search for the semipalindromic androgen receptor-binding element (ARE) consensus sequence GG(A)/(T)ACAnnnTGTTCT in the proximal hHa7 promoter revealed three putative ARE motifs. Electrophoretic mobility shift assays demonstrated the specific binding of AR to all three hHa7 AREs. Their function as AR-responsive elements, either individually or in concert within the hHa7 promoter, could be further confirmed by transfection studies with or without an AR expression vector in PtK2 and prostate PC3-Arwt cells, respectively in the presence or absence of a synthetic androgen. Our study detected hHa7 as the first gene in hair follicle trichocytes whose expression appears to be directly regulated by androgens. As such, hHa7 represents a marker for androgen action on hair follicles and might be a suitable tool for investigations of androgen-dependent hair disorders.

Androgens↗

Physiology of the vellus hair follicle: hair growth and sebum excretion.

The growth of vellus hair and the secretion of sebum from vellus hair follicles were measured on the forehead, cheek, chest, shoulder and back of healthy men and women aged 15-30 years. Hair growth was assessed by computerized image-analysis of photographs and sebum excretion by the use of Sebutape followed by image analysis. The density of vellus hairs and the percentage of growing hairs were higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on the forehead compared with 85 hairs/cm2 with 31.5% growing hairs on the back). The rate of growth ranged from 0.03 mm/day on the forehead to 0.13 mm/day on the back. The maximum length of vellus hair significantly decreased with age; otherwise hair growth was not affected by age or sex. Some variations in hair growth and sebum secretion were observed over a period of 3 months, but no consistent rhythms were detected. There was no obvious link between vellus hair growth and sebum excretion.

Adolescent↗

The vellus hair follicle in acne: hair growth and sebum excretion.

In this study we investigated the activity of the vellus hair follicle in acne. Hair growth and sebum excretion in vellus hair follicles were measured on the forehead and back of men, and on the forehead, cheek, and back of women with acne. Hair growth was assessed by computerized image analysis (phototrichogram), and sebum excretion by computer analysis using Sebutape. In patients with acne, marked differences were revealed when results were compared with recent data from healthy persons. In particular, the mean growth rate of vellus hairs was higher, whereas the percentage of anagen hairs was lower, and the duration of the anagen phase shorter in patients with acne than in healthy individuals. Hair growth and sebum excretion depended significantly (P < 0.01) on the anatomical site (forehead 414 hairs/cm2, 0.053 mm/day, 34%; back 93 hairs/cm2, 0.16 mm/day, 21%). In addition, analysis of hair growth revealed significantly higher values in females than in males for (i) percentage of anagen hairs (P > 0.01), (ii) for vellus hair length (P < 0.05), and (iii) for the duration of the anagen phase (P < 0.01). The present study demonstrates that the activity of the vellus hair follicle is influenced by acne, and vice versa, and therefore its role in the aetiopathogenesis of acne should be reconsidered.

Acne Vulgaris↗

Survival rate according to grafted density of Korean one-hair follicular units with a hair transplant implanter: Experience with four patients.

BACKGROUND: The survival rate of grafted hairs in hair transplantation has been frequently discussed by many hair-transplant surgeons. Several factors, including skill of doctors and assistants and the amount of perifollicular connective tissue, are suggested to have predictive values in foretelling the eventual quantity of hair growth. OBJECTIVE: The purpose of this study is to determine survival rate according to density of Korean one-hair follicular units grafted with a KNU implanter. METHODS: We designed four templates of 1 cm2 made by tattooing two templates on each side of empty frontoparietal recesses in four Korean patients with male pattern alopecia (beyond Norwood-Hamilton-Type IIIa). One-hair follicular units were prepared from occiput and we grafted 20, 30, 40, and 50 one-hair follicular units using a KNU implanter on each template, respectively, and counted the number of surviving hairs after 10 months. RESULTS: The survival rate of 20 and 30 grafts per template was higher than that of 40 and 50 grafts. CONCLUSION: We think that 30 one-hair follicular units grafted with a KNU implanter is the proper density for better survival in Korean hair transplantation, and repeated sessions will be necessary for a better final result. However, we need further evaluation with a larger number of participants to overcome the small sample size and limitation of one-hair follicular unit grafts. The authors have indicated no significant interest with commercial supporters.

Adult↗

[Immunohistochemical study on the keratin expression in generating rat hair tissues using anti-hair keratin monoclonal antibodies].

To investigate keratin expressions of generating rat hair tissues, monoclonal antibodies, HKN-2, 4, 5 and 6, were immunohistochemically applied on the skin specimens from 19-day-old rat fetus, newborn, 3-day-old and 7-day-old rats. In anagen hair tissues of 7-day-old rats, HKN-2 reacted with developing cells of the medulla, cortex, hair cuticle and inner and outer root sheaths. In the epidermis, HKN-2 reacted with spinous through horny cells. HKN-4 displayed a broad reactivity with all of the skin epithelial cells including hair tissue. These reactions were first seen in hair peg stage. HKN-2 and 4 first showed strong reactions with the innermost cell layer of the outer root sheath in anagen hair tissues of newborn rats. Reactivities by HKN-5 and 6 were localized in hair tissues in rats; however, HKN-5 showed no reaction with the innermost cell layer of the outer root sheath. HKN-5 and 6 showed no reaction with hair tissue before anagen. It is concluded that hair germ is different from epidermal basal cells in keratin expressions, that hair-specific keratins seem to be produced after the morphological differentiation of each layer, and that the innermost cell layer may differ from other outer root sheath since hair generation.

Animals↗

Hypotrichosis, hair structure defects, hypercysteine hair and glucosuria: a new genetic syndrome?

Structural hair changes may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder. We report a 22-month-old Turkish girl and her 10-month-old brother, whose scalp hair became fragile and sparse at about 6-7 months of age. Glucosuria, without diabetes or kidney disease, was detected 3-4 months later. Clinical examination revealed normal physical and mental development, and an analysis of plucked hairs showed dysplastic and broken hair shafts. Polarizing microscopy and scanning electron microscopic studies revealed torsion, and irregularities and impressions of the hair shaft, as seen in pili torti, trichorrhexis nodosa and pseudomonilethrix. Analysis of the amino-acid composition of the hair demonstrated a significant reduction of sulphonic cysteic acid and an elevated cysteine and lanthionine content in the girl, and elevated lanthionine levels in her brother. Electrophoretic analysis of the girl's hair proteins revealed a normal composition but a high extractability of hair proteins. The triad of hypotrichosis, structural hair-shaft defects and abnormal amino-acid composition, accompanied by glucosuria without diabetes, may represent a new genetic syndrome.

Amino Acids↗

An ultrastuctural study of hair fiber damage and restoration following treatment with permanent hair dye.

INTRODUCTION: Hair fibers are comprised of non-nucleated keratinocytes and are biologically dead. Clinical damage to the hair shaft occurs with the application of hair dye. Whether this damage can be repaired and the time frame involved is of interest and may help to determine the optimal interval between repeat applications. AIMS AND METHODS: Ultrastructural changes of hair shafts after application of permanent hair dye were observed sequentially in a 26-year-old woman. The dye contained p-phenylenediamine, m-aminophenol, resorcin and hydrogen peroxide as an oxidizer. Scanning and transmission electron microscopy was performed immediately before application of the hair dye and again at 30 min, 1 h, 3 h, 6 h, 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks. RESULTS: The hair showed cuticular swelling with focal degeneration. In some places there was exposure of the hair cortex due to extensive cuticular detachment. There were many holes of various size in the endocuticle, small focal lacunae along the intercellular space and an ill-defined A-layer especially beneath the area of cuticular detachment. The exocuticle appeared normal. The findings were most dramatic in the 6 h and 1 day specimens and tended to improve gradually thereafter. The 8 week specimen showed near complete restoration of the hair cuticle and return to the precoloring state. CONCLUSION: Hair returns to its precoloring state and this requires 8 weeks.

Adult↗

Hair growth cycle affects hair follicle destruction by ruby laser pulses.

It has been shown that normal mode ruby laser pulses (694 nm) are effective in selectively destroying brown or black pigmented hair follicles in adult Caucasians. This study investigated how the various stages of the hair follicle growth cycle influence follicle destruction by ruby laser treatment, using a model of predictable synchronous hair growth cycles in the infantile and adolescent mice. A range of ruby laser pulse fluences was delivered during different stages of the hair growth cycle, followed by histologic and gross observations of the injury and regrowth of hair. Actively growing and pigmented anagen stage hair follicles were sensitive to hair removal by normal mode ruby laser exposure, whereas catagen and telogen stage hair follicles were resistant to laser irradiation. Selective thermal injury to follicles was observed histologically, and hair regrowth was fluence dependent. In animals exposed during anagen, intermediate fluences induced nonscarring alopecia, whereas high fluences induced scarring alopecia. The findings of this study suggest treatment strategies for optimal laser hair removal.

Alopecia↗

[Effects of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro].

OBJECTIVE: To investigate the effect of water soluble extracts of traditional Chinese herbs on growth of mouse hair follicles and hair bulb cells in vitro. METHODS: Mouse hair follicles and hair bulb cells were cultured in Williams E medium with (experimental groups) or without (control group) water soluble extracts of Chinese herbs; the experimental group was further divided into mixture and single herb groups. Hair growth was observed by microscopy and growth activity of hair bulb cells was detected by MTT colorimetric assay. RESULT: On day 7 of culture, the hair growth in the mixture groups was faster than that in the control group (P<0.05). On day 3 and 5 of culture, the cell growth activity in the mixture groups was greater than that in the control group (P<0.05). While the hair growth and the cell growth activity between the single herb groups and the control group were not significantly different. CONCLUSION: The water soluble extracts of mixed traditional Chinese medicines can promote the growth of mouse hair in vitro and stimulate the proliferation of hair bulb cells; while those of the single traditional Chinese herb have no effect.

Angelica sinensis↗

Correlation between tryptophan and hair pigmentation in human hair.

The concentration of tryptophan in human hair of various colours is determined in order to study their correlation with hair pigmentation. The mean levels of this amino acid in hair samples are higher in men than in women. Therefore, sex influences the content of tryptophan in human hair. In addition, age influences the distribution, the highest levels are observed in the 1-5 year age-group and in ageing subjects in the groups up to 61-80 years in both sexes. The hair samples subdivided, according the colour, into blond, dark blond, red, light brown, brown, black, grey, and white demonstrate that in both sexes the concentrations of tryptophan are higher in brown and black hair than in blond hair. However, the tryptophan levels are highest in grey and white hair, showing that tryptophan accumulates among hair fibres with age. Therefore, there is a correlation between tryptophan content and hair pigmentation.

Adolescent↗

Hair zinc and copper: relationship to hair type and serum concentrations in children and adolescents.

The zinc and copper serum and hair concentrations of 691 3-18-y-old girls and boys previously determined as a part of the Multicentre Study of Atherosclerosis Precursors in Finnish Children and Adolescents were further analyzed in order to find a possible association between these two zinc and copper indices. The influence of hair color and the diameter of individual hair strands on hair concentrations were studied by the analysis of covariance. Hair color and serum zinc concentrations were found to be associated with hair zinc concentrations in boys. Such an association was not found for zinc and copper concentrations in girls. Hair vs serum concentrations in different age and hair color groups did not show however, a significant relationship either in copper or in zinc concentrations. The subjects with very low or high serum zinc or copper concentrations did not usually have extreme hair concentrations and vice versa. However, there were some subjects with low or high serum concentrations associated with low or high hair concentrations.

Adolescent↗

Hair cell replacement in avian vestibular epithelium: supporting cell to type I hair cell.

Previous investigations have demonstrated that the sensory epithelium of the avian vestibular system possesses the capacity to replace hair cells both on an ongoing basis and following severe damage. Supporting cells, within the sensory epithelium, are believed to be the progenitors of the regenerated hair cells. In the present study we describe the series of events leading to the formation of a regenerated vestibular hair cell in post-hatched birds. Young chickens received injections of streptomycin sulfate in order to damage the sensory epithelium of the vestibular system. These injections were followed by injections of the cell proliferation marker tritiated-thymidine. At predetermined intervals, the animals were killed, and the vestibular organs were processed for tissue autoradiography. Our results confirm that hair cells originate from supporting cells. The data also indicate that postmitotic cells migrate towards the lumen of the epithelium where they differentiate into Type II hair cells. At a later time, some of the new Type II hair cells further differentiate into Type I hair cells. These results suggest that both types of avian vestibular hair cells have a common ancestor. The data also provide evidence in support of the hypothesis that calyx enclosed Type I hair cells, only present in birds and mammals, are a more differentiated stage of Type II hair cells.

Animals↗

In vivo induction of hair growth by dermal cells isolated from hair follicles after extended organ culture.

Successful hair follicle organ culture has been established for some time, but hair growth in vitro is limited and generally terminates prematurely in comparison with in vivo. The reasons why growth stops in culture are as yet unknown. In this investigation, adult rat vibrissa follicles for which growth in culture is limited to about 10 d, were maintained in vitro for a minimum of 20 d after the hair shaft stopped growing. The pattern of fiber growth and long-term follicle pathology reflected the initial hair cycle stage at the time of isolation. Furthermore, there was evidence that a group of follicles put into culture when in late anagen were attempting to cycle in vitro. Microscopy showed that, in spite of widespread pathologic changes to the follicle epithelium, dermal cells in the follicle showed remarkable resilience. Their viability was confirmed when primary cell cultures were established from isolated dermal tissue. These cells labeled positively for alpha-smooth muscle actin, an established marker of hair follicle dermal cell phenotype in vitro. Moreover, isolated dermal tissue induced hair growth when implanted into inactivated hair follicles in vivo. These data confirm that the cessation in hair growth is not due to a loss of the inductive capacity in the dermal component. Long-term organ culture may provide opportunities to investigate factors that are expressed or lost during hair growth cessation. In addition it may be possible to develop this method further to obtain a reliable and predictable model of hair follicle cycling in vitro.

Animals↗