Molecular basis of hair cell loss

Mechanisms that lead to the death of hair cells are reviewed. Exposure to noise, the use of ototoxic drugs that damage the cochlea and old age are accompanied by hair cell death. Outer hair cells are often more susceptible than inner hair cells, partly because of an intrinsically greater susceptibility; high frequency cells are also more vulnerable. A common factor in hair cell loss following age-related changes and exposure to ototoxic drugs or high noise levels is the generation of reactive oxygen species, which can trigger intrinsic apoptosis (the mitochondrial pathway). However, hair cell death is sometimes produced via an extracellular signal pathway triggering extrinsic apoptosis. Necrosis and necroptosis also play a role and, in various situations in which cochlear damage occurs, a balance exists between these possible routes of cell death, with no one mechanism being exclusively activated. Finally, the numerous studies on these mechanisms of hair cell death have led to the identification of many potential therapeutic agents, some of which have been used to attempt to treat people exposed to damaging events, although clinical trials are not yet conclusive. Continued work in this area is likely to lead to clinical treatments that could be used to prevent or ameliorate hearing loss.     

The booming business of hair loss

The need for effective hair loss treatments has fostered research and the emergence of several biotechnology companies. Pharmacological approaches, although competitive, have been surpassed by cell-based therapies, which remain clinically immature. But are the current efforts enough for the hairy goal, or will additional strategies be required?     

Methods of hair loss evaluation in patients with endocrine disorders

Hair loss may accompany several endocrine disorders, including hypopituitarism, hypothyreosis, hyperthyreosis, hypoparathyroidism, diabetes mellitus, growth hormone deficiency, hyperprolactinaemia, polycystic ovary syndrome, SAHA syndrome, congenital adrenal hyperplasia, Cushing syndrome, or virilising tumours. Most patients with endocrine disorders present with diffuse non-scarring alopecia, such as anagen effluvium, telogen effluvium or androgenetic alopecia. Focal non-scarring alopecia, such as alopecia areata coexisting with autoimmune thyroiditis, is less frequent and scarring alopecia is a rare finding in patients with endocrine abnormalities. In some cases an endocrine disorder may be suspected based on dermatological findings during hair loss evaluation. Classic methods of hair evaluation include hair weighing, pull test, wash test, the trichogram, and histopathological examination. Newly developed non-invasive diagnostic techniques include the phototrichogram, trichoscan, trichoscopy, and reflectance confocal microscopy.     

Hair analysis for drugs of abuse XIX. Determination of ephedrine and its homologs in rat hair and human hair

A sensitive GC-MS method was developed for the quantitative analysis of ephedrine (EP), phenylpropanolamine (PPA) and methylephedrine (ME) in animal and human hair. After washing with 0.1% sodium dodecyl sulfate, hair samples (10 mg) were added with deuterated internal standards, extracted by 1-h sonication and over night soaking in 2 ml of 5 M HCl-methanol (1:20) at room temperature. Following evaporation of the liquid phase, the residue was dissolved in phosphate buffer solution (pH 6.0) and purified using a solid-phase extraction procedure with Bond Elut Certify columns. Two types of derivatization were compared - using trifluoroacetic anhydride (TFAA) and pentafluoropropionic anhydride (PFPA) - for discrimination of EP and methamphetamine (MA). Derivatized extracts were analyzed by GC-MS in the EI mode using a capillary column (OV-1 equivalent). From the results comparing three GC-MS conditions, PFP-derivatives separated with a temperature gradient of 20°C/min from 60°C to 280°C gave the best resolution between EP and MA. ME was analyzed as a trimethylsilyl derivative using N,O-bis-trimethylsilyl acetamide at the above GC condition. The assay was linear from 0.5 to 50 ng/mg (r=0.998) and capable of detecting less than 50 pg of derivatized EP, PPA and ME on-column. Intra-assay precision was characterized by C.V. values from 5 to 16% in the concentration range of 1–10 ng/mg hair. The method was used for the quantitative determination of EP, PPA and ME in the hair obtained from three rats with dark brown hair after ten intraperitoneal injections (5 mg/kg/day) of the three drugs and from three male and one female volunteers with black hair after an oral dose of 50 mg/day of EP-HCl for three days. Hair samples were collected by shaving from the back of rats and cutting from the scalp of humans 28 days after the first dose. The incorporation rates of EP, PPA and ME into hair (the ratios of [hair concentration] to [AUC]) obtained from the animal experiment were 0.10, 0.07 and 0.03, respectively, which are a little lower than those (0.14, 0.10 and 0.04) of their desoxy-compounds, MA, amphetamine and dimethylamphetamine. EP was detected at an average of 2.25 ng/mg (n=4) in human scalp hair and at a range of 1–29 ng/mg (n=3) in human beard hair until day 14, but its metabolite (PPA) was at a trace level in the hair of the four subjects. The method was successfully used for detection of ME and EP in the hair of a neonate and its mother who was abusing Bron syrup containing ME during the pregnancy.     

Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

The present study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 h a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into four groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by auditory brainstem response (ABR) and compound action potential (CAP) recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed 1 day, 1 week, and 1 month after noise exposure. After MTMI noise exposure, the amplitudes of ABR I and III waves were suppressed. The CAP threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement, or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss (HHL), which is partially reversible after leaving the noise environment; and MTMI noise-induced HHL is associated with inner hair cell ribbon synapses.     

Hair cycle dynamics: the case of the human hair follicle

The existence of a growth and regeneration cycle makes the hair follicle a true paradigm of tissue homeostasis. Analysis of about 9000 cycles led us to propose a stochastic model of human hair dynamics. The existence of hair cycles implies that stem cells must be cyclically activated and hair melanin unit has to be renewed. Using different markers, we were able to identify two distinct epithelial stem cell reservoirs, located in the upper and lower thirds of the anagen hair follicle outer root sheath. These two reservoirs fuse during the regression phase and individualize again in the new forming anagen hair follicle. Using a set of antibodies specific of melanocyte lineage and melanogenesis, pigmentation unit turnover was followed throughout the entire hair cycle. In the terminal anagen hair, active melanocytes were localized on top of the dermal papilla, while amelanotic melanocytes were identified in the upper third of the outer root sheath (ORS). Those amelanotic melanocytes located in upper ORS probably represented a melanocyte reservoir for successive hair generation, since at the induction of anagen phase, some melanocytes were committed to cell division and melanogenesis was turned on, but only in the nascent hair bulb, close to the dermal papilla.     

Blood amino acid compartmentation in men and women with different degrees of obesity

The role of blood cells in the interorgan transport of amino acids and the important size of such a pool has lead us to investigate the possibility that obesity causes alterations in amino acid blood compartmentation in humans and that such alterations show gender-linked differences given the special features of the obese state for each gender. We determined the blood levels of amino acids in whole blood and in the blood cell compartment of 42 men and 46 women. Subjects were classified according to their body mass index (BMI) into one of three groups: lean, overweight, or obese. Obesity was found to increase the levels of blood amino acids in both men and women, although not in the same way: In men, moderate overweight was accompanied by a significant increase of the amino acid blood levels, which were practically unchanged by a greater BMI; however, in women this same increase was observed only in the obese group. This effect is more marked in the cell compartment, where these alterations are actually reflected because plasma contribution values do not change as a whole. In conclusion, total blood and blood cell amino acids were altered in obesity, but in a different way, in both men and women depending on the degree of obesity. This profile of changes is seen to be particularly marked in the cellular pool, which contributes to enhancing the importance of this pool in the handling of amino acids.     

Overexpression of XIAP inhibits cisplatin-induced hair cell loss

Cisplatin is a platinum-containing drug with ototoxicity commonly used clinically and has significant efficacy against a variety of solid tumors. One of the most important mechanisms of ototoxicity is that cisplatin induces apoptosis of hair cells. According to relevant literature, X-linked inhibitor of apoptosis protein (XIAP, anti-apoptotic protein) could inhibit the apoptotic pathway. We hypothesized that this protein might protect cochlear hair cells from cisplatin-induced injury. To figure it out, we treated cochlea of normal mice with various concentrations of cisplatin to observe the response and morphology of hair cells and determine a reasonable concentration. Next, Western Blot and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) experiments were conducted to make an investigation about the expression of XIAP protein and mRNA. In addition, we constructed and identified XIAP overexpressing mice. Finally, we treated cochlear tissues of normal and overexpressing mice with cisplatin to investigate the cyto-protection of XIAP on hair cells, respectively. It was found that 50 μmol/L cisplatin resulted in significant loss and disorganization of hair cells, while simultaneously downregulating the protein and mRNA of XIAP. In XIAP overexpressing mice, the loss and disorganization of hair cells were significantly lessened. These results showed that XIAP can lessen cisplatin-induced hair cell loss and play a role in otoprotection.     

Evaluation of ivermectin for treatment of hair loss syndrome in black-tailed deer

Since 1997, numerous Columbian black-tailed deer (Odocoileus hemionus columbianus) in western Washington (USA) have developed a hair loss syndrome that often preceded emaciation, debilitation, pneumonia, and death. To study this syndrome, eight affected free-ranging Columbian black-tailed deer fawns were captured from western Washington in February 1999 to determine the effect of ivermectin treatment. Fecal examinations indicated that the internal parasites were Dictyocaulus viviparus, Parelaphostrongylus sp., Trichuris sp., Moniezia sp., Eimeria spp., and gastrointestinal strongyles. Biting lice (Tricholipeurus parallelus) were observed on all deer, with up to 5 lice/cm(2) on the index areas counted. Three deer were treated with ivermectin subcutaneously at doses between 0.2 and 1.3 mg/kg of body weight monthly for four consecutive months, and five control deer received no anthelmintic treatment. Complete blood counts, parasite evaluations, weight gains, and hair loss evaluations were used to assess effectiveness of treatment. Two untreated deer died during the experiment compared with no deaths among the three treated deer. Treated deer gained significantly more weight (P<0.05) than the untreated deer (22.4 vs. 12.6 kg, respectively) that survived the experiment, had significantly fewer parasite eggs and larvae (P<0.05) in feces and significantly fewer nematodes (P<0.05) at necropsy, and regrew their hair at a faster rate than untreated deer. Lice and all nematode eggs and larval stages in feces were eliminated or greatly reduced following treatment. On the basis of these data, excessive louse populations, gastrointestinal nematodes, and the lung-worms Parelaphostrongylus sp. and D. viviparus, might be important predisposing factors for this hair loss condition and death of affected animals.     

Prevention and correction of temporal hair loss in rhytidectomy

Routine incisions in the temporal area for rhytidectomy often remove hair-bearing skin anterior to the ear. This results in a cosmetic deformity, making the surgical intervention clearly visible. This is especially problematic for revision rhytidectomy or for patients with naturally high hairlines. This article describes a systematic approach to the temporal hairline and introduces a novel, hair-bearing, transposition flap that corrects iatrogenic loss of the preauricular tuft of hair.     

MONW phenotype is associated with advanced colorectal adenoma in Korean men

The aim of this study was to investigate whether there was a relationship between colorectal adenoma and metabolically obese but normal weight (MONW) among Korean men and women. The MONW phenotype is defined as a BMI <25, but fulfilling the metabolic syndrome (MS) criteria with a modified waist circumference (≥90 cm for men and ≥85 cm for women) appropriate for Korean. A total of 3,430 subjects (2,263 men and 1,167 women; 23-75 years old) were included in the study. Colorectal adenomas were diagnosed in 775 men and 199 women. The rate of advanced adenomas in males was 24.3% and in females 21.1%. A significant association between MONW and advanced colorectal adenoma was found in men (age-adjusted odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.06-3.47) but not in women (age-adjusted OR = 1.80, 95% CI: 0.50-6.45). The findings suggest that men with MONW may have an increased risk of developing advanced colorectal adenoma whereas this does not seem true for females.