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Hair and nail cortisol is increasingly studied as a physiologic proxy for chronic stress response. Glucocorticoid use is an expected confounder for cortisol measurement, yet there remains little evidence of whether external cortisol use should be subject to exclusion in study subjects. In a group of 209 youth (15-22 year-olds), we analyzed hair and fingernail cortisol concentrations. We assessed topical, nasal, oral, and injectable glucocorticoid use via a questionnaire. Extensively validated methods were used for hair and nail cortisol extraction and measurements. The median value of hair cortisol was 10.2 pg/mg (n=200), and the median value of nail cortisol was 7.06 pg/mg (n=203). Topical glucocorticoid use significantly increased hair and nail cortisol concentrations (p<0.005). Hair and nail cortisol concentrations were positively associated (p<0.0001, n=194). Spearman correlation coefficients demonstrated that the positive correlation between hair and nail cortisol values was higher in participants who used external glucocorticoids. Topical glucocorticoids moderated the association between hair and nail cortisol values (p=0.006). Based on these findings, we recommend that the assessment of topical glucocorticoid use must be performed when collecting hair/nail samples and that subjects reporting glucocorticoid use should be excluded from all future hair and nail cortisol studies; also, all outliers must be excluded to account for glucocorticoid medication underreporting and yet-unknown confounders., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest. KB declares a significant financial interest in Stress Bioanalytics, LLC, which currently performs HCC and NCC measurements in numerous projects. The present work was completed a year before the creation of Stress Bioanalytics LLC., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Urine, hair and nail samples were collected from a population of both sex aged from 40 to 87 years in Niška Banja (227 km south of Belgrade, Serbia) with a high level of natural radioactivity (HLNRA). To assess and monitor the public exposure, urine samples for each subject (24 h period) were collected and concentration of uranium (U) was analysed using alpha-particle spectrometry. Human hair and nails considered as bio-indicators of the public exposure to radionuclides over a long period of months or even years and concentration of U was determined using inductively coupled plasma-mass spectrometry. The mean concentrations of U in urine, hair and nail were 123 ng/L, 17 ng/g and 8 ng/g, respectively. There was a large variation and may be due to geological origin., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The abuse of drugs has become a serious social problem worldwide. Amphetamine-type stimulants such as methamphetamine are recreationally abused and can cause toxic effects in the body. Unfortunately, death from drug poisoning can occur due to careless intake. In postmortem examinations, the distribution of drugs in an entire organ gives valuable information for evaluating their toxicity. We developed methods to measure the distribution of drugs in organs using LC/MS and matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The complementary use of the two methods provides more detailed information on the distribution and concentration of drugs in organs because the accurate quantification in LC/MS and small spatial resolution in MALDI-IMS are combined. On the other hand, it is important to elucidate the drug intake history of suspects and victims in drug-facilitated crimes (DFCs). Hair and nail samples are often used to confirm chronic drug intake because ingested drugs can stably remain in these specimens over several months. However, it is impossible to determine the day of drug ingestion in conventional segmental analysis of bulk samples. Therefore, we developed methods to cut hair strands at 0.4-mm intervals and nails at 0.2-mm intervals, which correspond to their respective growth rates over 1-2 d, to analyze the drugs in each segment efficiently using LC/MS. The microsegmental hair analysis method is applied to estimate the day of drug ingestion in DFC investigations. These methods could be applied to measure the distribution of compounds in various solid samples.

Aims: Measurement of ethyl glucuronide (EtG) in nail, as a biomarker for alcohol intake, has recently been suggested as alternative to measurement in hair. The aim of this study was to compare levels of EtG in nail and hair, and to investigate the elimination kinetics of EtG in fingernails during an alcohol abstinent period., Methods: Overall, 40 subjects (median estimated daily intake of ethanol (EDI) 92.5 g/day) were recruited from an alcohol rehabilitation clinic. Nail and hair samples were collected at inclusion and nail clippings were collected every 7-10th day for up to 12 weeks., Results: All patients showed higher nail EtG/EDI ratios compared to hair EtG/EDI ratios (P < 0.001). The median value of the ratios between EtG in nail and EtG in hair was 5.0 (range: 1.07-56.1). There was a significant correlation between nail EtG/EDI and hair EtG/EDI (Spearman's ρ = 0.638, P < 0.001). EtG disappeared from nails after ~2 months of abstinence and the median calculated EtG half-life in nail clippings was 13.3 days (range: 5.5-29.0). There was a significant correlation between the time elapsed to last positive sample for nail EtG and nail EtG levels at time of inclusion (Spearman's ρ = 0.449, P = 0.004)., Conclusion: The present data indicate that EtG cut-off levels in nails should be higher compared to the established 30 pg/mg EtG cut-off in hair representing heavy drinking. EtG may disappear faster from nail than expected from nail growth physiology., Short Summary: Nails are an alternative matrix to hair when measuring ethyl glucuronide (EtG). The present study indicate that EtG cut-off levels in nails should be higher compared to the established 30 pg/mg EtG cut-off in hair representing heavy drinking, and EtG may disappear faster from nail than expected., (© The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved)

In the present study, a new extraction method based on acid digestion and SPE clean-up (Oasis Wax) was developed for measuring four PFR metabolites (i.e. dibutyl phosphate (DBP), diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl)phosphate (BDCPP) and bis(2-butoxy ethyl) phosphate (BBEP)) in hair and nails. The method optimization was done according to a combinatorial design (Taguchi) where several parameters were efficiently optimized. Precision was lower for hair than for nails (RSD % 18 and 28%). Recoveries were >74%. High DBP levels in procedural blanks were traced back to the use of SPE cartridges. Therefore a new SPE pre-treatment was tested, reducing significantly DBP levels (<1 ng). Levels of the PFR metabolites were measured in scalp hair, finger, and toe nails collected over two months in two volunteers (female and male). DPhP levels were extremely high (in μg/g range) in both finger and toe nails in the female. BDCPP and BBEP were the minor metabolites detected in nails (average levels of 28-64 ng/g and <2.2-4.1 ng/g, respectively). DPhP was the only metabolite detected in hair (0.23-0.25 ng/g). Results showed that there is a possible contribution from both an external (via deposition) and an internal exposure, however it was not possible to fully understand their extent. Since there were no records of lifestyle and due to the small sample size, the major exposure source could not be addressed here. Nevertheless, there is evidence that hair and nails (finger and toe) might be good indicators of human exposure to PFRs, especially to TPhP., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The thermoluminescence (TL) and optically stimulated luminescence (OSL) properties of human nails and hairs containing α-keratin proteins have been investigated. For the present studies, black hairs and finger nails were selectively collected from individuals with ages between 25 and 35 years. The collected hairs/nails were cut to a size of < 1 mm and cleaned with distilled water to remove dirt and other potential physical sources of contamination. All samples were optically beached with 470 nm of LED light at 60 mW/cm(2) intensity and irradiated by a (60)Co γ source. The hair and nail samples showed overlapping multiple TL glow peaks in the temperature range from 70 to 210 ° C. Continuous wave (CW)-OSL measurements of hair samples at a wavelength of 470 nm showed the presence of two distinct OSL components with photoionization cross section (PIC) values of about 1.65 × 10(-18) cm(2) and about 3.48 × 10(-19) cm(2), while measurements of nail samples showed PIC values of about 6.98 × 10(-18) cm(2) and about 8.7 × 10(-19) cm(2), respectively. This difference in PIC values for hair and nail samples from the same individual is attributed to different arrangement of α-keratin protein concentrations in the samples. The OSL sensitivity was found to vary ± 5 times among nail and hair samples from different individuals, with significant fading (60% in 11 h) at room temperature. The remaining signal (after fading) can be useful for dose estimation when a highly sensitive OSL reader is used. In the absorbed dose range of 100 mGy-100 Gy, both the TL and OSL signals of hair and nail samples showed linear dose dependence. The results obtained in the present study suggest that OSL using hair and nail samples may provide a supplementary method of dose estimation in radiological and nuclear emergencies.

An organic solvent-free method was developed to extract some potentially toxic metals, as complexed with 2-(5-bromo-2-pyridylazo)-5-(diethylamino)phenol, from different real samples prior to their determination by microsampling flame atomic absorption spectrometry. The method, named ionic liquid-based ultrasound-enhanced air-assisted liquid-liquid microextraction (IL-USE-AALLME), is based upon withdrawing and pushing out a mixture of an aqueous sample and an IL (as the extraction solvent) for several times into a conical test tube using a single syringe, placed in an ultrasound bath (as the enhancing mass transfer agent) during the extraction process. Different effective parameters were studied, and at the optimized conditions, limits of detection, linear dynamic ranges, and enrichment factors were ranged from 0.9 to 2.2 μg L(-1), 3.0 to 1023 μg L(-1), and 20 ± 2 to 22 ± 2, respectively. After optimization, the method was successfully applied to determine Pb(2+), Cu(2+), Co(2+), Ni(2+), and Cr(3+) in different biological (hair and nail), vegetable (coriander, parsley, and tarragon), fruit juice (apple, orange, and peach), and water (tap, mineral, and wastewater) samples. The proposed method was compared with two other IL-based and disperser solvent-free methods (i.e., IL-based air-assisted liquid-liquid microextraction and IL-based ultrasound-assisted emulsification microextraction) to demonstrate its performance.

Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2-2.4 for MDMA and 0.85-0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044-0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

The etiology of cancer is complex, and the disturbances in toxic and essential metals homeostasis are among many of the factors that lead to the development of malignancy. The aim of this study is to investigate the relationship between cancer risk and element status as well as cancer risk and external factors, such as diet, smoking and drinking habits, in order to support diagnosis of cancer. The samples of hair and nails obtained from patients with larynx cancer and healthy subjects were analyzed. Essential elements (Ca, Cr, Mg, Zn, Cu, Mn, and Fe), besides toxic metals (Cd, Co, and Pb), were determined using inductively coupled plasma atomic emission spectrometry (ICP-OES) and mass spectrometry (ICP-MS) techniques. The concentration of essential elements was from 1.5- (Zn) to 4.7-fold (Fe) higher in hair and from 2.4- to 3.3-fold higher in the nails of the control group compared to the patients, while the opposite trend was observed for the heavy metals. The differences between two groups in the level of metals (except for Zn) were statistically significant (p < 0.05). The association of cancer with metals and other factors was evaluated using various statistical methods, for which the best predictions were obtained using logistic regression, artificial neural networks and canonical discriminant analysis. The classifiers constructed using the data from a survey of diet and lifestyle, and analysis of elements in hair and nails, can be useful tools for estimating cancer risk and early screening of the disease.

Human populace of Assam, India repeatedly exposed to high concentration of iron in groundwater results in adverse health effects like hemochromatosis, liver cirrhosis and siderosis. In the present study, human hair and nail analysis were carried out to establish a possible relationship between iron toxicity and its deposition among the residents. Nail and hair iron concentrations ranged from 28.2 to 1046μgg(-1) (n=114) and 26.5-838 (n=108)μgg(-1) levels, respectively, among all the study participants. The iron content of the groundwater (421-5340μgL(-1)) (n=64) used for drinking purposes was positively correlated with both nail (r=0.788, p<0.0001) and hair (r=0.709, p<0.0001) iron concentrations. Age- and sex-matched controls corresponding to each group were selected from population residing in other parts of the country where groundwater does not have excess iron. All the study groups included population drinking iron-contaminated water above the WHO/BIS limit (>300µgL(-1)) for 5 years (Group 1), for more than 5-10 years (Group 2) and for more than 10 years (Group 3). Results suggested that the participants consuming groundwater exceeding the WHO limit of iron had significantly more iron accumulation than those using groundwater containing ≤300μgL(-1) iron (p<0.01). There was statistically higher concentration of iron in the nail samples than the hair samples in all the study groups (p<0.01). There was a positive correlation in iron concentration and the residence time of the participants (p<0.01). Iron levels in the male participants were significantly higher than the female participants in the present study (p<0.01). The current findings are sufficiently compelling to warrant more extensive study of iron exposure through drinking water and adverse effects to the human in the areas where iron concentration is high., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T>C variant (p.Phe274Ser) in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC) analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/hypotrichosis simplex (ADWH). Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.

Millions of people suffer from superficial infections caused by dermatophytes. Intriguingly, these filamentous fungi exclusively infect keratin-rich host structures such as hair, nails, and skin. Keratin is a hard, compact protein, and its utilization by dermatophytes for growth has long been discussed as a major virulence attribute. Here, we provide strong support for the hypothesis that keratin degradation is facilitated by the secretion of the reducing agent sulfite, which can cleave keratin-stabilizing cystine bonds. We discovered that sulfite is produced by dermatophytes from environmental cysteine, which at elevated concentrations is toxic for microbes and humans. We found that sulfite formation from cysteine relies on the key enzyme cysteine dioxygenase Cdo1. Sulfite secretion is supported by the sulfite efflux pump Ssu1. Targeted mutagenesis proved that dermatophyte mutants in either Cdo1 or Ssu1 were highly growth-sensitive to cysteine, and mutants in Ssu1 were specifically sensitive to sulfite. Most notably, dermatophyte mutants in Cdo1 and Ssu1 were specifically growth-defective on hair and nails. As keratin is rich in cysteine, our identified mechanism of cysteine conversion and sulfite efflux supports both cysteine and sulfite tolerance per se and progression of keratin degradation. These in vitro findings have implications for dermatophyte infection pathogenesis.

Because of the disadvantages of invasive sampling, it is desirable to explore non-invasive matrices for human biomonitoring of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). The aim of this study was to evaluate the application of nail, hair and urine for human biomonitoring of PFOS and PFOA. The concentrations of PFOS and PFOA in matched nail, hair, urine and serum samples collected from 64 donors were measured. The chemicals of interest were detected with high detection frequency in these matrices (90%-100%) except for PFOA in urine samples (56%). Generally, the gender influences on the levels of PFOS and PFOA in these non-invasive matrices were in agreement with that in serum. For PFOS, the coefficients of Spearman correlation between serum samples and nail, hair and urine samples were 0.786 (p<0.001), 0.545 (p<0.001) and 0.302 (p<0.05), respectively. For PFOA, the correlation was only observed between nail samples and serum samples with a correlation coefficient of 0.299 (p<0.05). The results suggested that nail has more potential than hair and urine to be applied in human biomonitoring for PFOS and PFOA in general populations., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Autism is a complex disorder which is heterogeneous in nature with varying degrees of severity for which no specific biological marker has been identified. Several studies are focused on the hair and nail protein pattern as a means to identify specific markers for the diagnosis of many childhood disorders like mental retardation, dyslexia, trichorrhexis nodosa, trichothiodystrophy, etc. The present study is one such approach in investigating the electrophoretic pattern of proteins in hard keratins and their percentage of nitration since nitric oxide production and nitration of tyrosine residues in proteins of autistic children are the emerging topic of research., Methods: We extracted and quantified the proteins from hair and nail samples of autistic children with different grades of severity, [low functioning autism (LFA), medium functioning autism (MFA), and high functioning autism (HFA)] and also from age- and sex-matched normal children. Protein pattern was evaluated by one-dimensional SDS-PAGE and the separated proteins were made to cross react with anti-nitro tyrosine antibody by Western blot analysis. Blood levels of TBARS, NO, GSH, vitamins A and C, SOD and GPx were also determined., Results: In the autistic groups, decreased concentration of protein in both hair and nail samples was observed. The SDS-PAGE analysis revealed that there was a significant decrease in both high and low sulfur proteins in the hair and nail extracts of autistic children and the Western blot analysis showed increased percentage of nitration of low sulfur proteins in autistic children when compared with normal children. Decreased levels of enzymatic and non-enzymatic antioxidants and increased concentration of TBARS and NO were also observed in the blood of autistic children. The LFA group showed more significant alteration (p<0.001) in the concentration of proteins (in hair and nail) and percentage of nitration when compared with HFA and controls., Conclusion: Lower protein content and higher percentage of nitration in hair and nail of autistic children correlated with their degrees of severity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The report presents the possibility of using an alternative material of determining citalopram and its metabolite (desmethylcitalopram) in hair and nails. Citalopram (Cipramil, Citaratio, Citaxin, Oropram, Cital, Cilon, Aurex) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class, employed in treatment of depression, prevention of depressive disorders recurrence and in some anxiety disorders. The investigations were performed using liquid chromatography coupled with electrospray-ionization mass spectrophotometry (LC-ESI-MS). In the course of the study, the authors developed a method for isolation and identification of Citaprolam and its metabolite (desmethylcitaprolam) from hair and nails. Determination were performed in hair and nail samples collected from individuals who had been administered citalopram in therapeutic doses at least for 12 months before sample collection. Hair and nail samples were obtained 4, 6, 9 and 15 months after discontinuing drug administration. The concentration of citalopram in nails was 0.40-10.49 ng/mg and the concentration of desmethylcitalopram was 0.32-3.70 ng/mg. In hair, citalopram concentration was 1.04-8.69 ng/mg and for desmethylcitalopram, the concentration range was 0.07-1.27 ng/mg.

Electron paramagnetic resonance (EPR) spectroscopy and imaging (EPRI) are deeply rooted in the basic and quantum physics, but the spectrum of their applications in modern experimental and clinical dermatology and cosmetology is surprisingly wide. The main aim of this review was to show the physical foundation, technical limitations and versatility of this method in skin studies. Free radical and metal ion detection, EPR dosimetry, melanin study, spin trapping, spin labelling, oximetry and NO-metry, EPR imaging, new generation methods of EPR and EPR/NMR hybrid technology used under ex vivo and in vivo regime are portrayed in the context of clinical and experimental skin research to study problems such as oxidative and nitrosative stress generated by UV or inflammation, skin oxygenation, hydration of corneal layer of epidermis, transport and metabolism of drugs and cosmeceutics, skin carcinogenesis, skin tumors and many others. A part of the paper is devoted to hair and nail research. The review of dermatological applications of EPR is supplemented with a handful of advice concerning practical aspects of EPR experimentation and usage of EPR reagents.

Human hair and nail are valuable materials for producing individual corresponding biocompatible materials. A rapid and convenient protein extraction method (Shindai method) and novel procedures for preparing their protein films from their extracts have been developed using human hair and nail. The effects of the human hair and nail proteins and their films on histamine release from rat peritoneal mast cells were investigated. Both protein solutions and their films, mainly consisting of keratins and matrix proteins, did not induce histamine release from the mast cells. Scanning electron microscopy (SEM) also showed that the mast cells were only slightly affected by adding the human hair and nail proteins or by incubating on their protein films. The IgE-dependent histamine release was inhibited by the hair and nail proteins and their films. Incubation of the mast cells with the hair and nail proteins prior to the addition of the IgE serum resulted in a high inhibition (50%) of the histamine release, while the inhibition was approximately 10% when the protein solutions were mixed with the mast cells after incubation with the IgE serum. These results suggest that the human hair and nail proteins and their films will be useful materials for antiallergic actions.

Very little is known about arsenic (As) metabolism in healthy populations that are not exposed to high concentrations of As in their food or water. Here we present a study with healthy volunteers from three different ethnic groups, residing in Leicester, UK, which reveals statistically significant differences in the levels of total As in urine and fingernail samples. Urine (n = 63), hair (n = 36) and fingernail (n = 36) samples from Asians, Somali Black-Africans and Whites were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectroscopy (GF-AAS). The results clearly show that the total concentrations of As in urine and fingernail samples of a Somali Black-African population (urine 7.2 microg/g creatinine; fingernails 723.1 microg/kg) are significantly (P < 0.05) different from the Asian (urine 24.5 microg/g creatinine; fingernails 153.9 microg/kg) and White groups (urine 20.9 microg/g creatinine; fingernails 177.0 microg/kg). The chemical speciation of As in the urine of the three groups was also measured using high performance liquid chromatography coupled to ICP-MS. This showed that the proportion of the total urinary As present as dimethylarsenate (DMA) was higher for the Somali Black-African group (50%) compared to the Asians (16%) and Whites (22%). However, there was no significant difference (P > 0.05) in the level of As in the hair samples from these three groups; Somali Black-Africans (116.0 microg/kg), Asians (117.4 microg/kg) and Whites (141.2 microg/kg). Significantly different levels of total As in fingernail and urine and a higher percentage of urinary DMA in the Somali Black-Africans are suggestive of a different pattern of As metabolism in this ethnic group.

In the hair of individuals with blood group AB, the level of blood group A glycosphingolipids is much lower than that of blood group B. We hypothesized that in hair, blood group A determinants are converted by alpha-N-acetylgalactosaminidase (alpha-NAGA, E.C.3.2.1.49) to H determinants. To address our hypothesis, the relative amount of ABH glycosphingolipids in hairs and nails of normal subjects, patients with Kanzaki disease, and heterozygous carriers of alpha-NAGA deficiency were analyzed by dot-blotting and enzyme-linked immunosorbent assay. In hair from normal subjects with blood group B, ABH glycosphingolipids consisted of 88% blood group B- and 12% blood group H glycosphingolipids. In blood group A subjects, 14% were group A- and 86% were group H glycosphingolipids. In Kanzaki patients, 81% were blood group A- and 19% were blood group H glycosphingolipids. In 2 alpha-NAGA deficiency carriers, the ABH glycosphingolipids consisted of 67% blood group A- and 33% blood group H glycosphingolipids. These results indicate that blood group A glycosphingolipids are catabolized to H glycosphingolipids by alpha-NAGA, resulting in lower levels of blood group A glycosphingolipids in the hair of normal subjects, and alpha-NAGA deficiency causes accumulation of blood group A glycosphingolipids in the hair of Kanzaki patients. This finding is of clinical relevance because it suggests that hair may be used to diagnose and assess the alpha-NAGA status of individuals.

The concentration of uranium in urine, hair, and nails due to continuous exposure through ingestion of drinking water was studied. The study population consisted of 205 individuals living in 134 different households in southern Finland where drinking water is supplied from private drilled wells. The population was selected to include a broad range of uranium daily intake from drinking water (0.03-2,775 microg d). The uranium content in drinking water, urine (overnight collection), hair and nails was determined by ICPMS. Uranium in urine was corrected for the matrix effects by use of thallium as an internal standard and adjusted by creatinine normalization. Hair and toenail samples were rinsed to remove external contamination prior to acid digestion and analysis. The uranium content in all excretion pathways was correlated with the uranium intake, particularly at elevated levels (> or =10 microg d) where drinking water was the major source of exposure to uranium. The median of the individual uranium absorption factors for urine, hair, and toenails were fu=0.003, fh=0.003, and fn=4 x 10, respectively. The association between the different bioassays was examined. The absorption factor, f1, was calculated for the population with an intake above 10 microg d and was below 0.01 for 72% of the study persons (range 0.0002 to 0.070). No statistically significant difference in f1 values was found between women and men. However, the absorption factor was higher among younger (< 60 y) than older (> or =60 y) subjects and among people with a lower exposure (below 100 microg d) than among those that ingest over 100 microg d.

The term "trichothiodystrophy" (TTD) covers several autosomal recessive diseases whose diagnostic hallmark is short, brittle hair low in sulfur and cystine because of impaired synthesis of high-sulfur matrix protein. Clinical symptoms associated with TTD represent a variable range of abnormalities in organs derived from ectoderm and neuroectoderm. Important laboratory tests of the hair for the diagnosis of TTD comprise polarizing microscopy ("tiger-tail" pattern), electron microscopy, and amino acids analysis of hydrolyzed hair with a special focus on cystine. However, only very few institutions determine the amino acid composition of human hair and nail clippings, which requires special sample preparation including hydrolysis. If no special precautions are taken, quantification of cysteine and cystine becomes inaccurate because of decomposition of these residues during hydrolysis. We therefore performed the sample work-up with azide-dependent oxidation which we have for the first time adapted for analysis of hair and nail clippings. With our control and parent data resembling published data on hair and nail samples, we obtained a decreased proportion of cysteine (half cystine, determined as cysteic acid) in materials obtained from a boy with TTD. Clearly, the method for the quantification of cysteine following sodium azide-dependent oxidation is a suitable and rather convenient approach to the quantification of cyst(e)ine and other amino acids in hair and nail proteins, and is a valuable contribution to the diagnosis of TTD.

Creatinine-corrected urine mercury measurements in spot urine samples are routinely used in monitoring workers exposed to inorganic mercury. However, mercury measurement in other non-invasive biological material has been used in some epidemiological studies. Dentists and dental nurses remain a group of workers with potential exposure to inorganic mercury through their handling of mercury-containing amalgam, although changes in work practices have reduced the current, likely exposure to mercury. Therefore, dental workers remain an occupational cohort in whom the value of using different biological media to identify exposure to low level inorganic mercury can be investigated. Samples of head hair, pubic hair, fingernails, toenails and urine were analysed for mercury content from a cohort of UK dentists (n=167) and a socioeconomically similar reference population (n=68) in whom any mercury exposure was primarily through diet. The mercury content in all biological material was significantly higher in the dental workers than in the control population (p<0.0001). The geometric mean and 90th percentile mercury concentrations in the urine samples from dentists were 1.7 and 7.3 micromol mol(-1) creatinine, respectively, with only one sample having a value at around the UK's Health and Safety Executive biological monitoring health guidance level of 20 micromol mol(-1) creatinine. Receiver operator characteristic analyses suggested that the ability of the biological material to discriminate between dentists and referents were fingernails>urine approximately equal to toenails>pubic hair approximately equal to head hair. Further investigation is warranted as to why fingernails appear to be such a good discriminator, possibly reflecting some contribution of direct finger contact with amalgam or contaminated surfaces rather than systemic incorporation of mercury into growing nails. Good correlation between head hair and pubic hair mercury levels in all subjects was obtained (r=0.832), which was significantly improved when hair samples weighing <10 mg were excluded (r=0.868). Therefore, under these exposure conditions and using the described pre-analytical washing steps, there is little influence from atmospheric contamination on the level of mercury content of head hair. The choice of non-invasive biological materials for mercury analysis depends on a number of considerations. These include the toxicokinetics of urinary mercury excretion, the growth rates of hair and nail, the nature and time-frame of exposure, and the fact that urine mercury may not reflect the body burden level from dietary methyl mercury. However, the data from this study suggests that urine mercury remains the most practical and sensitive means of monitoring low level occupational exposure to inorganic mercury.

In contrast to surface lipids originating from the sebaceous glands, membrane-forming integral lipids occur in keratinized tissues of skin, and skin appendages like fingernail plates or scalp hair. After removal of lipids of sebaceous origin by exhaustive solvent extraction, lyophilizing and hydrolyzing fingernail plate and scalp hair samples, fractions of integral cholesterol (CH) and cholesterol sulfate (CS) were quantified using gas chromatography. We studied these bound lipids and the serum lipids of 70 healthy subjects, aged 20.1 to 92.0 years. We observed higher amounts of CS in hair clippings of men than of women (775+/-241 vs 662+/-239 nmol/g hair, respectively). The highest amounts of CS were found in men with serum LDL-CH > 4.14 mmol/L; this subgroup also showed the highest CH values in fingernail clippings (2293+/-621 nmol/g nail). However, analysis of integral lipids of hair and fingernail plate clippings had little significance in detecting hypercholesterolemia in normal persons. An increase in integral CH levels in fingernail clippings with donor age was noted, independently of variations in serum CH or LDL-CH. This correlation proved to be significant in men (R=0.43), but not in women (R=0.38). In contrast, in women but not in men we found donor age correlated with internal CH of hair samples (R=0.43) and with CS of nail plates (R=-0.59), independently of serum CH or LDL-CH variations. This age-dependent decrease in CS levels might explain the previously observed higher incidence of brittle nails in women. Obviously, the metabolism of internal lipids CH and CS in fingernail and scalp hair differs between genders, and shows age-associated changes.

The hard-keratin-containing portion of the murine hair shaft displays a positive immunoreactivity with an antibody against the soft epithelial keratin, K17. The K17-expressing cell population is located in the medulla compartment of the hair. Consistent with this observation, K17-containing cells also occur in the presumptive medulla precursor cells located in the hair follicle matrix. Western blot analysis of hair extracts prepared from a number of mouse strains confirms this observation and suggests that K17 expression in the hair shaft is a general trait in this species. The expression of K17 in human hair extracts is restricted to eyebrow and facial hair samples. These are the major sites for the occurrence of the pili torti (twisted hair) phenotype in the type 2 (Jackson-Lawler) form of pachyonychia congenita, previously shown to arise from inherited K17 mutations. Given that all forms of pachyonychia congenita show an involvement of the nail, we compared the expression of the two other genes mutated in pachyonychia congenita diseases, K6 and K16, with that of K17 in human nail. All three keratins are abundantly expressed within the nail bed epithelium, whereas K17 protein is expressed in the nail matrix, which contains the epithelial cell precursors for the nail plate. Our data suggest a role for K17 in the formation and maintenance of various skin appendages and directly support the concept that pachyonychia congenita is a disease of the nail bed.

The suitability of the selenium concentrations in blood plasma, red blood cells, hair and nails to serve as indicators for the selenium status in the main body pools and for the chemical forms of the element ingested was investigated in an animal model. Selenium-deficient male rats, fed a methionine-supplemented low selenium diet, were replenished over a period of 3 months by repeated oral administration of 75Se-labeled sodium selenite or L-selenomethionine in amounts equivalent to the intake from diets with selenium concentrations of 0.3 mg/kg and 2 mg/kg. As the tracer was found to reflect the selenium distribution in the main compartments, quantitative selenium analysis in whole body, liver, skeletal muscle, heart and the monitor materials in the four groups was carried out by measuring the 75Se activity. The blood selenium level was the most suitable parameter for assessing the selenium status in the liver, while the nail selenium concentration was most suited for whole body, skeletal muscle and heart. The differences in the amount and chemical form of dietary selenium were best reflected by the ratios of the selenium levels in hair and plasma or in nails and plasma. The results suggest that with adequate or high selenium intake it might be possible to obtain information on the selenium status of the main body compartments by evaluating the selenium concentrations in several appropriate monitor materials.

Heavy metals in biological samples: nails, teeth, and hair were examined during 1991-1993. Investigations of biological samples (hair n = 249 samples, teeth n = 145, nails n = 80 samples) were provided for inhabitants of selected towns in Beskid Slaski. The towns are small mountain towns in southern Poland: Wista, Szczyrk, Istebna, Koniakow, and Jaworzynka. The analysis of ANOVA and MANOVA variances were used for biological samples in the context of age, sex, and type of samples for 12 elements (Pb, Cd, Cr, Zn, Fe, Cu, Mn, Ni, Co, Ca, Na, and K). The matrix correlation and cluster analysis were applied to explain the behavior of metals in human hair, teeth, and nails.

Vanadium was determined by radiochemical neutron activation analysis (RNAA) with proven accuracy in urine of workers occupationally exposed to vanadium-rich dust in a vanadium pentoxide production plant, and values in the range of 3.02-762 ng/mL (median 33.0 ng/mL) were found. In a control group consisting of administrative workers of the plant, urinary vanadium levels were found in the range of 1.05-53.4 ng/mL (median 2.53 ng/mL), whereas in an another control group of occupationally nonexposed persons, these values amounted to 0.066-0.489 ng/mL (median 0.212 ng/mL). Accuracy of the results was tested by analysis of reference material IAEA A-13 Animal Blood and NIST SRM-1515 Apple Leaves, and very good agreement was found with literature and the NIST certified values, respectively. Unlike urine, no significant differences were found for cystine levels in fingernails and hair of exposed and control persons.

The hair follicle contains several components with different programs of differentiation some of which include the synthesis of a cornified envelope. Our interest in cornified envelope precursors of the epidermis prompted an investigation of the location of several of these in the hair follicle. Monoclonal antibodies to the precursor proteins involucrin, pancornulin and sciellin were reacted with frozen section of skin and their localization detected by fluorescein tagged antibodies or the peroxidase technique. Staining was observed in the ostium and isthmus of the hair follicle using all 3 antibodies and was similar to that observed in epidermis. Staining of the inner root sheath was also observed with all 3 antibodies. In the case of the antibody to sciellin, the reaction was clearly localized to the cell periphery using special fixation. The other antibodies did not react by this technique and appeared to show cytoplasmic staining. Similar studies with nail also showed reactivity, but the distribution of the 3 proteins in the different regions of the nail varied. The role of the envelope precursors in the hair follicle remains to be established. The inner root sheath does not appear to have a fully developed cornified envelopes and isopeptide bond formation occurs primarily in the cytoplasm. These proteins may have a role similar to trichohyalin in cornification of the inner root sheath.

Noninvasive techniques to monitor selenium (Se) status at higher intake levels should be developed if Se supplements are to be given to human subjects as possible anti-cancer agents. Hair and nails have been suggested as indices of Se status because they are easily obtained, transported and stored. However, there has been little research on the potential influence of such factors as dietary Se intake or nutritional status on the levels of Se in hair and nails. Here we report the effects of chemical form of dietary Se and of methionine (Met) status on the Se content of rat hair and nails. Rats were fed diets containing 0.5, 1.5 or 2.5 micrograms/g of Se as sodium selenate (Na2SeO4) or L-selenomethionine (SeMet) for 8 wk. Hair and nail Se retention was two- to threefold greater when dietary SeMet was fed. Hair and nail Se levels increased as liver and muscle Se retention increased in rats fed SeMet, whereas in rats fed Na2SeO4, hair, nails and liver accumulated Se but muscle Se levels remained relatively unchanged. In a second experiment, rats were fed diets containing 0.1, 0.5 or 2.5 micrograms/g of Se as Na2SeO4 or SeMet, +/- added Met (0.3%) for 6 (+Met) or 7 (-Met) wk. Hair and nail Se retention was greater when Met was deficient than when this amino acid was not limiting. These results suggest that factors other than dietary Se intake affect hair and nail Se content and that these tissues should be used with caution for Se status assessment purposes.

The hair-forming cells (trichocytes) and the mature hair contain four major trichocytic cytokeratins from each of the subfamilies, basic (Hb1-4) and acidic (Ha1-4); these are related - but not identical - to the epithelial cytokeratins. Here we show, by biochemical methods and immunofluorescence microscopy using antibodies specific for either epithelial or trichocyte cytokeratins, that the same set of hair-type cytokeratins, including two newly identified minor components, designated Hax (type I) and Hbx (type II), are also expressed in cells forming nails, in the filiform papillae of the dorsal surface of human and bovine tongue, and, most surprisingly, in some cells of the epithelial reticulum of bovine and human thymus. By double-label immunofluorescence microscopy, we also show that the expression of the two subsets of cytokeratins, i.e., the epithelial and the trichocytic ones, is not necessarily mutually exclusive, but that certain cells of hair follicles, nail matrix and bed, lingual papillae, and the nonlymphoid cell system of the thymus contain both trichocytic and certain epithelial cytokeratins. This indicates that these cells coexpress representatives of both kinds of cytokeratin. Implications of these findings with respect to problems of regulatory control of cytokeratin synthesis in tissue development and differentiation, and the possible functional meaning of the occurrence of trichocytic cytokeratins in such histologically diverse tissues, are discussed.

Although numerous hair proteins have been studied biochemically and many have been sequenced, relatively little is known about their in situ distribution and differential expression in the hair follicle. To study this problem, we have prepared several mouse monoclonal antibodies that recognize different classes of human hair proteins. Our AE14 antibody recognizes a group of 10-25K hair proteins which most likely corresponds to the high sulfur proteins, our AE12 and AE13 antibodies define a doublet of 44K/46K proteins which are relatively acidic and correspond to the type I low sulfur keratins, and our previously described AE3 antibody recognizes a triplet of 56K/59K/60K proteins which are relatively basic and correspond to the type II low sulfur keratins. Using these and other immunological probes, we demonstrate the following. The acidic 44K/46K and basic 56-60K hair keratins appear coordinately in upper corticle and cuticle cells. The 10-25K, AE14-reactive antigens are expressed only later in more matured corticle cells that are in the upper elongation zone, but these antigens are absent from cuticle cells. The 10-nm filaments of the inner root sheath cells fail to react with any of our monoclonal antibodies and are therefore immunologically distinguishable from the cortex and cuticle filaments. Nail plate contains 10-20% soft keratins in addition to large amounts of hair keratins; these soft keratins have been identified as the 50K/58K and 48K/56K keratin pairs. Taken together, these results suggest that the precursor cells of hair cortex and nail plate share a major pathway of epithelial differentiation, and that the acidic 44K/46K and basic 56-60K hard keratins represent a co-expressed keratin pair which can serve as a marker for hair/nail-type epithelial differentiation.