Why is hair curly?—Deductions from the structure and the biomechanics of the mature hair shaft

The final shape of a head hair is predetermined through a variety of factors during its formation in the follicle. These are genetic pathways, specific growth factors, cell differentiation and segregation, etc, with spatial as well as chronological dynamics. The cortex of hair consists of two major cell groups. These are characterized by parallel (para-type) or roughly helical arrangements (ortho-type) of the intermediate filaments (IF). There are also cell-specific differences in the disulphide content, that is, of the cross-link density of the IF-associated matrix proteins. Given the current state of the academic discussion, we consider it as timely to support and broaden the view that, the structural differences of the cell types together with their lateral segregation are the main driving factor of curl formation. The mechanical effects, which derive thereof, are triggered in the transition zone of the follicle, that is, upon formation of the mature hair shaft. Furthermore, an irregular, “flat” cross section of the hair shaft is shown to be a synergistic but not determining factor of curl formation. The degree of cell type segregation along the mature hair shaft together with dynamic changes of the location of the plane of segregation, namely in a non-circular cross section can account for very complex curl patterns. Against the background of these views, we argue that contributions to hair curl are implausible, if they relate to physical mechanisms which are active below the transition zone from the living to the mature (dead) hair.     

Do the factors associated with successful contact tracing of patients with gonorrhoea and Chlamydia differ?

OBJECTIVE: To assess and compare factors which may be associated with successful contact tracing in patients with gonorrhoea and chlamydia. STUDY DESIGN: Prospective observational study of patients attending a genitourinary medicine clinic with a diagnosis of gonorrhoea or chlamydia. Multivariate analysis model including demographic, socioeconomic, and behavioural variables. RESULTS: The attendance of at least one sexual contact was associated with naming more contacts for patients with gonorrhoea (OR 1.44, 95% CI 1.04-2.01). A history of gonorrhoea was associated with successful contact tracing for patients with chlamydia (OR 1.46, 95% CI 1.12-1.9). Successful contact tracing, as defined by at least one confirmed contact attendance after the index case, was not associated with age, sex, sexual orientation, history of chlamydia, use of condoms, marital status, ethnicity, or socioeconomic status for either gonorrhoea or chlamydia. CONCLUSIONS: Differences in the composition of the core groups infected with gonorrhoea and chlamydia are not explained by differences in contact tracing success. In the clinic setting studied, the outcome of contact tracing was not associated with a variety of demographic, socioeconomic, and behaviour factors.     

Mechanobiology and cell tensegrity: the root of ethnic hair curling?

Background The hair shape, either straight, crimp, or curly, is basically under genetic influence. It is possibly altered by some drugs such as cytostatic agents. In addition, specific innate molecular characteristics are modulated by some cosmetic procedures to reshape the hair shafts. Aim To revisit the possible implication of mechanobiology and cell tensegrity in shaping ethnic hair. Materials and methods Optical and scanning electron microscopy of hairs. Results It is generally held that the cross‐section shape of hair is related to differences in the global aspect of the hair shaft. A possible biologic link between these features may rely on shaping cell tensegrity at any portion of the hair shaft. Cell tensegrity encompasses all intrinsic and extrinsic forces responsible for the three‐dimensional arrangement of intracellular macromolecules. Conclusion We offer as a hypothesis that the hair shape in part depends on the organization of the cell proliferation in the hair matrix. This review gathers observations supporting the involvement of cell tensegrity in shaping the hair shaft.     

Microneedling for the treatment of hair loss?

Microneedling is a minimally invasive dermatological procedure in which fine needles are rolled over the skin to puncture the stratum corneum. This therapy is used to induce collagen formation, neovascularization and growth factor production of treated areas. It has been used in a wide range of dermatologic conditions, including androgenetic alopecia (AGA) and alopecia areata, among others. While there are a limited number of studies examining this therapy in the use of hair loss, microneedling has been successfully paired with other hair growth promoting therapies, such as minoxidil, platelet‐rich plasma and topical steroids, and shown to stimulate hair follicle growth. It is thought that microneedling facilitates penetration of such first‐line medications, and this is one mechanism by which it promotes hair growth. To date, the area most studied and with the most success has been microneedling treatment of AGA. While the current evidence does not allow one to conclude superiority of microneedling over existing standard therapies for hair loss, microneedling shows some promise in improving hair growth, especially in combination with existing techniques. This review summarizes the current literature regarding microneedling in the treatment of alopecia and calls for further studies to define a standard treatment protocol.     

Do androgens influence hair growth by altering the paracrine factors secreted by dermal papilla cells?

Androgens regulate many aspects of human hair growth in both sexes. After puberty they transform tiny vellus follicles in many areas, e.g. the face, to terminal ones producing long, thick, pigmented hairs. In genetically predisposed individuals, androgens also cause the reverse transformation of terminal scalp follicles into vellus ones, causing balding. In the current hypothesis for androgen action, androgens control most follicular cells indirectly acting via the mesenchyme-derived dermal papilla which regulates many aspects of follicular activity. In this model androgens binding to androgen receptors in dermal papilla cells alter their production of regulatory molecules which influence other follicular components; these molecules may be soluble paracrine factors and/or extracellular matrix proteins. This hypothesis is supported by immunohistochemical localisation of androgen receptors in dermal papilla cell nuclei and the demonstrations that androgen receptor content and testosterone metabolism patterns of cultured dermal papilla cells from various body sites reflect hair growth in androgen-insensitivity syndromes. The next question is whether androgens alter the paracrine factors secreted by dermal papilla cells. Cultured dermal papilla cells do release soluble, proteinaceous factors into their media which stimulate the growth of keratinocytes and other dermal papilla cells. This mitogenic potential can cross species from humans to rodents. Importantly, testosterone in vitro stimulates the mitogenic potential of beard cells, but in contrast inhibits production by balding scalp cells reflecting their in vivo androgenic responses. Since androgens in vitro do alter the secretion of paracrine factors the current focus lies in identifying specific factors produced, e.g. IGF-I and stem cell factor (SCF), using ELISA and RT-PCR, and comparing their expression in cells from follicles with varying responses to androgens in vivo or under androgen stimulation in vitro. This should lead to greater understanding of androgen action and enable the development of better treatment for androgen-potentiated disorders.     

Do human dermal adipocytes switch from lipogenesis in anagen to lipophagy and lipolysis during catagen in the human hair cycle?

In murine skin, dermal white adipose tissue (DWAT) undergoes fluctuations in size across the hair cycle, whereas changes in size, function and metabolism of dermal adipocytes (DAs) during the human scalp hair cycle remain unexplored. Transmission electron microscopy results suggest that during anagen‐catagen transition, human DAs co‐opt the autophagy machinery to undergo lipophagy within their lipid droplets. Whole‐mount staining of hair follicles (HFs) and surrounding DWAT for the autophagy marker LC3B confirms the increased presence of LC3B+ lipid droplets adjacent to catagen HFs; moreover, DWAT around catagen HFs engages in greater glycerol release compared to DWAT surrounding anagen HFs. Thus, we hypothesize that human DAs switch from lipogenesis during anagen to lipophagy together with lipolysis during catagen. We propose various experiments to further prove this hypothesis, whose systematic exploration should help to better characterize the functions of human DWAT and its communication with the HF.     

Parathyroid hormone‐related peptide and the hair cycle – is it the agonists or the antagonists that cause hair growth?

While the effects of PTHrP have been studied for almost 20 years, most of these studies have focused on effects on the termination of the anagen phase, giving an incomplete picture of the overall effect of PTHrP on the hair cycle. PTHrP was determined in several experimental models to promote transition of hair follicles from anagen to catagen phase, which by itself would suggest that PTHrP blockade might prolong the anagen phase and promote hair growth. However, clinical trials with topically applied PTHrP antagonists have been disappointing, leading to a reconsideration of this model. Additional studies performed in mouse models where hair follicles are damaged (alopecia areata, chemotherapy‐induced alopecia) suggest that PTHrP has effects early in the hair cycle as well, promoting hair follicles’ entry into anagen phase and initiates the hair cycle. While the mechanism of this has yet to be elucidated, it may involve activation of the Wnt pathway. Thus, the overall effect of PTHrP is to stimulate and accelerate the hair cycle, and in the more clinically relevant models of hair loss where hair follicles have been damaged or become quiescent, it is the agonists, not the antagonists, which would be expected to promote hair growth.     

A niche in the spotlight: Could external factors critically disturb hair follicle homeostasis and contribute to inflammatory hair follicle diseases?

The anatomy of the hair follicle and the dynamics of its barrier provide a special space for interactions between macromolecules and the underlying tissue. Translocation across the hair follicle epithelium and immune recognition has been confirmed for proteins, nucleic acids, engineered particles, virus particles and others. Tissue responses can be modulated by pro-inflammatory stimuli as demonstrated in penetration and transcutaneous immunization studies. Even under physiological conditions, hair follicle openings are filled with exogenous material ranging from macromolecules, engineered particles to natural particles including diverse communities of microbes. The exposed position of the infundibulum suggests that local inflammatory insults could disturb the finely tuned balance and may trigger downstream responses that initiate or facilitate local outbreaks of inflammatory hair diseases typically occurring in close spatial association with the infundibulum as observed in cicatricial alopecia. The question as to how microbial colonization or deposition of contaminants on the surface of the hair follicle epithelium interact with the barrier status under the influence of individual predisposition may help us understand local flare-ups of inflammatory hair diseases. Specifically, learning more about skin barrier alterations in the different types of inflammatory hair diseases and cross-talk with exogenous compounds could give new insights in this less explored aspect of hair follicle homeostasis. Such knowledge may not only be used to develop supportive measures to maintain a healthy scalp. It may have wider implications for our understanding on how external factors influence inflammation and immunological responses in the skin.     

Is the loose anagen hair syndrome a keratin disorder? A clinical and molecular study

OBJECTIVES: To report the clinical features of the loose anagen hair syndrome and to test the hypothesis that the typical gap between the hair and the inner root sheath may result from hereditary defects in the inner root sheath or the apposed companion layer. DESIGN: Case series. SETTING: A pediatric dermatology unit (referral center). PATIENTS: A consecutive sample of 17 children (13 girls). For 9 of them and their first-degree relatives, molecular analyses were performed in the K6HF gene with 50 appropriate controls. INTERVENTION: Minoxidil therapy (5% lotion) in 11 patients for 1 to 12 months. MAIN OUTCOME MEASURES: Clinical and follow-up features and determination of mutations in the K6HF gene. RESULTS: Most patients had easily pluckable hair with no sign of scalp inflammation or scarring. Ten patients seldom cut their hair, and 4 had unmanageable hair. One patient had hypodontia. Two patients had an additional clinical phenotype of diffuse partial woolly hair. The family history was positive for loose anagen hair syndrome in 5 patients. Marked improvement was noted after treatment with 5% minoxidil lotion in 7 of the 11 patients treated. Polymerase chain reaction analysis of the gene segments encoding the alpha-helical 1A and 2B subdomains of K6hf, the type II cytokeratin exclusively expressed in the companion layer, was performed in 9 families. In 3 of these 9 families, a heterozygous glutamic acid and lysine mutation, E337K, was identified in the L2 linker region of K6HF. CONCLUSIONS: Diffuse partial woolly hair can be associated with loose anagen hair syndrome. A keratin mutation, E337K in K6HF, was possibly causative in 3 of the 9 families studied. Another keratin, and possibly the type I partner of K6hf, could be responsible for loose anagen hair syndrome in other patients, or the gene involved may be a minor gene.     

Kenogen. A new phase of the hair cycle?

BACKGROUND: A novel phenomenon has been described by the phototrichogram: the emptiness of the follicle after teloptosis. We called this phenomenon kenogen, from the Greek kappaepsilonnuóvarsigma, 'empty'. OBJECTIVE: To describe the kenogen phase in its details. METHODS: Analysis of the existing literature. RESULTS: The original observation in 2 women was confirmed in 10 balding and non-balding males studied for 14 years in whom kenogen lasted about 4 months increasing up to about 7 months and affecting 80% of all hair cycles. In 2 women with progressing androgenetic alopecia studied for 2 years, kenogen involved 22% of the hair follicles, lasting from 3 months to 1 year. In a prepubertal boy studied for 1 year, it involved 8% of hairs and lasted about 2 months. CONCLUSION: During kenogen, the hair follicle rests physiologically, but duration and frequency are greater in androgenetic alopecia, possibly accounting for baldness. In addition to the classical cycle, the hair follicle may follow an alternative route during which the telogen phase, not accompanied by a coincident new early anagen, ends with teloptosis leaving the follicle empty.     

Getting to the root of scales,feather and hair: As deep as odontodes?

While every jawed vertebrate, or its recent ancestor, possesses teeth, skin appendages are characteristic of the living clades: skin denticles (odontodes) in chondrichthyans, dermal scales in teleosts, ducted multicellular glands in amphibians, epidermal scales in squamates, feathers in birds and hair‐gland complexes in mammals, all of them showing a dense periodic patterning. While the odontode origin of teleost scales is generally accepted, the origin of both feather and hair is still debated. They appear long before mammals and birds, at least in the Jurassic in mammaliaforms and in ornithodires (pterosaurs and dinosaurs), and are contemporary to scales of early squamates. Epidermal scales might have appeared several times in evolution, and basal amniotes could not have developed a scaled dry integument, as the function of hair follicle requires its association with glands. In areas such as amnion, cornea or plantar pads, the formation of feather and hair is prevented early in embryogenesis, but can be easily reverted by playing with the Wnt/BMP/Shh pathways, which both imply the plasticity and the default competence of ectoderm. Conserved ectodermal/mesenchymal signalling pathways lead to placode formation, while later the crosstalk differs, as well as the final performing tissue(s): both epidermis and dermis for teeth and odontodes, mostly dermis for teleosts scales and only epidermis for squamate scale, feather and hair. We therefore suggest that tooth, dermal scale, epidermal scale, feather and hair evolved in parallel from a shared placode/dermal cell unit, which was present in a common ancestor, an early vertebrate gnathostome with odontodes, ca. 420 million years ago.     

Stüve-Wiedemann syndrome with multiple eruptive vellus hair cysts and clefted tongue

Stüve-Wiedemann syndrome is a rare autosomal recessive congenital primary skeletal dysplasia, characterized by small stature, bowed long bones, joint restrictions, hyperthermic episodes, dysautonomia, and respiratory and feeding difficulties, that usually leads to early mortality. Cutaneous manifestations have rarely been reported. We report the case of a girl with Stüve-Wiedemann syndrome presenting with progressive development of multiple eruptive vellus hair cysts.     

Does the minimal phototoxic dose after 8‐methoxypsoralen baths correlate with the individual’s skin phototype?

BACKGROUND/AIMS: Up to now no data have been available concerning whether there is a significant correlation between skin phototypes and the minimum phototoxic dose (MPD) after bath water delivery of 8-MOP. METHODS: The skin phototype of each of 46 patients was determined based on the individual past history of solar-induced burning and tanning. In addition, the MPD of each patient was assesed after photosensitization with a warm water bath (37 degrees C, 98.6 degrees F) containing 1.0 mg/l 8-methoxypsoralen (8-MOP). Statistical analysis was performed using a Mann-Whitney U-test and Spearman rank order correlation. RESULTS: The median MPD in patients with skin phototype II was 2.0 J/cm2 (range < or =0.5 to > or =3.5) versus 1.5 J/cm2 (range 1.0 to > or =3.5) in patients with skin phototype III. There was a considerable overlap between both groups. No significant difference was detected comparing both groups (P=0.7326) and Spearman rank order correlation revealed no correlation between skin phototype and MPD. CONCLUSION: Erythemal sensitivity in PUVA bath therapy, measured as MPD, is not correlated with sun-reactive skin phototype in skin types II and III. Thus skin phototype is not a suitable indicator for the initial UVA dose in PUVA bath photochemotherapy.