Global Monitoring of Persistent Organic Pollutants (POPs) Using Seabird Preen Gland Oil.

Situated at high positions on marine food webs, seabirds accumulate high concentrations of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), and hexachlorocyclohexanes (HCHs). Our previous studies proposed the usefulness of seabirds preen gland oil as a nondestructive biomonitoring tool. The present study applied this approach to 154 adult birds of 24 species collected from 11 locations during 2005-2016 to demonstrate the utility of preen gland oil as a tool for global monitoring POPs, i.e., PCBs, DDTs, and HCHs. Concentrations of the POPs were higher in the Northern Hemisphere than in the Southern Hemisphere. In particular, ∑20PCBs and∑DDTs were highly concentrated in European shags (Phalacrocorax aristotelis) and Japanese cormorants (Phalacrocorax capillatus), explainable by a diet of benthic fishes. Higher concentrations of γ-HCH were detected in species from the polar regions, possibly reflecting the recent exposure and global distillation of ∑HCHs. We examined the relationship between age and POP concentrations in preen gland oil from 20 male European shags, aged 3-16 years old. Concentrations and compositions of POPs were not related to age. We also examined sex differences in the POP concentrations from 24 streaked shearwaters (Calonectris leucomelas) and did not detect a sex bias. These results underline the importance of the geographic concentration patterns and the dietary behavior as determinants species-specific POPs concentrations in preen gland oil.

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice.

Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and Kras(G12D) mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity.

Aryl Hydrocarbon Receptor Activation in Acne Vulgaris Skin: A Case Series from the Region of Naples, Italy.

BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown. MATERIALS AND METHODS: We explored the expression of CYP1A1 by immunohistochemistry in the acne lesions of 16 patients living in the region of Naples, Italy, where epidemiological studies have suggested a possibly increased exposure to environmental dioxins. A composite score to outline potential components of the chloracne/MADISH histological pattern was used. RESULTS: CYP1A1 expression was observed in 11 lesions (69%) and was distributed in sebaceous glands, follicular epithelium, cystic wall and endothelial cells. The histological score for chloracne/MADISH was 'likely' in 3 cases and 'possible' in 11 cases. Compared to current data on CYP1A1 expression in the skin of 67 patients with proven exposure to AhR agonists, these data indicate a high incidence of AhR activation in this series. CONCLUSION: This is the first study analysing AhR activation in skin in a series of patients from a hospital-based acne clinic. It provides information for future controlled prospective studies. The significance of CYP1A1 expression in terms of AhR ligand exposure is discussed.

Neuro-folliculo-sebaceous cystic hamartoma is a unique entity.

Folliculosebaceous cystic hamartoma (FSCH) is a distinct type of cutaneous hamartoma of pilosebaceous origin that usually occurs on the face. For FSCH, other parts have been reported such as the genital area, and the trunk. A 50-year-old woman presented with an asymptomatic dome-shaped scalp nodule. The clinical diagnosis was pilar cyst or tumor. Histopathological assessment showed FSCH with absolute neural component as the only mesenchymal stroma, leading to the diagnosis of folliculosebaceous cystic neural hamartoma. To the best of our knowledge, absolute neural stroma in FSCH has not been reported previously in the literature.

Age-associated skin changes in innate immunity markers reflect a complex interaction between aging mechanisms in the sebaceous gland.

Skin aging is the most apparent form of senescence and could reflect the aging of inner organs. Molecular changes involved in innate immunity signaling, tumorigenesis, and inflammation were studied. Protein levels were evaluated based on the immunohistochemistry of the skin of 42 young and old individuals. The investigated molecules (peroxisome proliferator-activated receptors-α and -γ, Toll-like receptor 4, and interleukin-6 and 8) were expressed in almost all skin compartments and exhibited significant aging-associated downregulation in epithelial tissues, mostly in the sebaceous glands, the sweat glands, and the epidermis. With the exception of interleukin-6 in the dermal tissue, no upregulation was detected in the aged group. The results obtained indicate an interesting interaction between different pathways of aging, namely defective stress responses, downregulated innate immunity responses, and activation of the tumorigenesis pathway, which was especially apparent in the sebaceous glands.

Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin.

OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.

Toker cells of the nipple are commonly associated with underlying sebaceous glands but not with lactiferous ducts.

AIMS: Toker cells are clear cells present in the squamous epithelium of the nipple of some women. In contrast to squamous epithelium, they are cytokeratin 7 (CK7) positive. The origin of these cells is not completely understood. It has been suggested that they may represent abortive glands or migratory ductal cells; and may be precursors of Paget's disease of the nipple. Our aim was to investigate the incidence and distribution of Toker cells and their relationship with lactiferous ducts. METHODS: We examined nipple sections from 100 consecutive mastectomies performed at Charing Cross hospital. New sections were stained for CK7 using the immunoperoxidase technique. RESULTS: Toker cells were identified in 11 cases. They were always clustered within the squamous epithelium superficial to sebaceous glands with no relationship with lactiferous ducts. Two cases in the study had Paget's disease and these were not associated with underlying sebaceous glands. CONCLUSIONS: This study suggests that Toker cells are more likely to be developmentally related to sebaceous glands rather than lactiferous ducts. This raises doubts about the presence of a relationship between Toker cells and the common forms of Paget's disease, as the latter are commonly seen in association with ductal carcinoma in situ (DCIS) involving underlying lactiferous ducts. Toker cells, however, may be related to a less common form of Paget's disease which is not associated with underlying DCIS.

Expression of caspase-14 and keratin-19 in the human epidermis and appendages during fetal skin development.

Caspase-14 is a seemingly non-apoptotic caspase involved in keratinocyte differentiation and cornification of the skin. Keratin-19 is an epithelial marker and a potential marker of epidermal stem cells that is expressed during human fetal skin development. We examined the immunohistochemical expression of caspase-14 in relation to CK-19 in the human fetal skin during development and perinatally, to assess their role in human skin maturation. Skin samples were received at autopsy. In the fetal epidermis, caspase-14 was predominantly expressed in the more differentiated layers, gradually disappearing from the basal layer toward term. By contrast, keratin-19 expression gradually decreased with epidermal maturation through gestation (rho = -0.949; p = 0.0001) and was a marker of the germinative layers. Keratin-19 was preserved in scarce basal cell nests at term and postnatally. Caspase-14 and keratin-19 were inversely expressed in the differentiating epidermal layers through gestation (p < 0.0001). Concerning the appendages, in hair follicles and sebaceous glands, caspase-14 located preferentially in the more differentiated layers of the inner root sheath, whereas keratin-19 was expressed in the outer sheath. Eccrine sweat glands showed a variable pattern of caspase-14 and keratin-19 expression. In conclusion, caspase-14 emerged as a marker of human skin differentiation during development, while keratin-19 marked the germinative epithelial layers in the fetal epidermis and appendages and possibly the nests of epidermal stem cells.

Proliferative and nonproliferative lesions of the rat and mouse mammary, Zymbal's, preputial, and clitoral glands.

The mammary gland of laboratory rodents is an important organ for the evaluation of effects of xenobiotics, especially those that perturb hormonal homeostasis or are potentially carcinogenic. Mammary gland cancer is a leading cause of human mortality and morbidity worldwide and is a subject of major research efforts utilizing rodent models. Zymbal's, preputial, and clitoral glands are standard tissues that are evaluated in animal models that enable human risk assessment of xenobiotics. A widely accepted and utilized international harmonization of nomenclature for mammary, Zymbal's, preputial, and clitoral gland lesions in laboratory animals will improve diagnostic alignment among regulatory and scientific research organizations and enrich international exchanges of information among toxicologists and pathologists.

"Onycholemmal carcinoma." An unusual case with apocrine and sebaceous differentiation. Are these tumors a microcystic nail bed carcinoma?

Subungual malignant epithelial tumors with tricholemmal keratinization have rarely been described as "malignant proliferating onycholemmal cyst" and "onycholemmal carcinoma (OC)." We report an additional case of a slow growing OC occurring on the middle finger of a 58-year-old man, which was unusual as it showed sebaceous-apocrine differentiation, in addition to a nail bed carcinoma with tricholemmal microcysts. We therefore consider the descriptive term of microcystic nail bed carcinoma more appropriate than OC. It is recognized that none of the rare cases of OC meet the classical additional criteria proposed by Headington for tricholemmal carcinoma, that is, lobular arrangement, peripheral palisading, thickened basement membrane, and glycogen-positive tumors cells. On the other hand, we suggest that the term follicular microcysts of the nail bed should be retained to describe the true nature of subungual epidermoid inclusions, which show usually a limited differentiation toward the follicular isthmus. Therefore, the previous cases of OC without sebaceous-apocrine differentiation could be best classified as a microcystic nail bed carcinoma arising from the follicular microcysts of the nail bed, with a limited differentiation toward the keratinization of the follicular isthmus.

Immunohistochemical study of calretinin in normal skin and cutaneous adnexal proliferations.

Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.

The fatty acid profile of the skin surface lipid layer in papulopustular rosacea.

BACKGROUND: Patients with papulopustular rosacea (PPR) frequently complain of dry, sensitive skin. We have previously demonstrated that patients with PPR have reduced skin surface hydration levels in the presence of normal sebum casual levels, suggesting that it may be the quality and not the quantity of sebum that plays a role in PPR. OBJECTIVES: To compare the sebaceous fatty acid composition of patients with PPR to that of controls with normal facial skin. METHODS: The sebaceous fatty acid composition of 25 patients with PPR and 24 age- and sex-matched controls was analysed by gas chromatography - mass spectrometry. Results Myristic acid (C14:0) was present in greater concentrations in PPR sebum, while the long chain saturated fatty acids arachidic acid (C20:0), behenic acid (C22:0), tricosanoic acid (C23:0) and lignoceric acid (C24:0) as well as the monounsaturated fatty acid cis-11-eicosanoic acid (C20:1) were present in the sebum of patients with PPR in lesser concentrations as compared with controls. CONCLUSIONS: There is increasing evidence that sebaceous fatty acids play a role in the maintenance of skin barrier integrity. We have shown for the first time that patients with PPR have an abnormal sebaceous fatty acid composition, with reduced levels of long chain saturated fatty acids. These new findings may have therapeutic implications for the development of sebum-modifying nonantibiotic treatments for patients with PPR.

Selective photothermolysis to target sebaceous glands: theoretical estimation of parameters and preliminary results using a free electron laser.

BACKGROUND AND OBJECTIVES: The success of permanent laser hair removal suggests that selective photothermolysis (SP) of sebaceous glands, another part of hair follicles, may also have merit. About 30% of sebum consists of fats with copious CH(2) bond content. SP was studied in vitro, using free electron laser (FEL) pulses at an infrared CH(2) vibrational absorption wavelength band. METHODS: Absorption spectra of natural and artificially prepared sebum were measured from 200 to 3,000 nm, to determine wavelengths potentially able to target sebaceous glands. The Jefferson National Accelerator superconducting FEL was used to measure photothermal excitation of aqueous gels, artificial sebum, pig skin, human scalp, and forehead skin (sebaceous sites). In vitro skin samples were exposed to FEL pulses from 1,620 to 1,720 nm, spot diameter 7-9.5 mm with exposure through a cold 4°C sapphire window in contact with the skin. Exposed and control tissue samples were stained using H&E, and nitroblue tetrazolium chloride staining (NBTC) was used to detect thermal denaturation. RESULTS: Natural and artificial sebum both had absorption peaks near 1,210, 1,728, 1,760, 2,306 and 2,346 nm. Laser-induced heating of artificial sebum was approximately twice that of water at 1,710 and 1,720 nm, and about 1.5× higher in human sebaceous glands than in water. Thermal camera imaging showed transient focal heating near sebaceous hair follicles. Histologically, skin samples exposed to ~1,700 nm, ~100-125 milliseconds pulses showed evidence of selective thermal damage to sebaceous glands. Sebaceous glands were positive for NBTC staining, without evidence of selective loss in samples exposed to the laser. Epidermis was undamaged in all samples. CONCLUSIONS: SP of sebaceous glands appears to be feasible. Potentially, optical pulses at ~1,720 or ~1,210 nm delivered with large beam diameter and appropriate skin cooling in approximately 0.1 seconds may provide an alternative treatment for acne.

Role of testosterone in stimulating seasonal changes in a potential avian chemosignal.

Songbird preen oil contains volatile and semivolatile compounds that may contain information about species, sex, individual identity, and season. We examined the relationship between testosterone (T) and the amounts of preen oil volatile and semivolatile compounds in wild and captive dark-eyed juncos (Junco hyemalis). In wild males and females, we observed an increase in volatile compound relative concentration early in the breeding season. This increase mirrored previously described seasonal elevation in T levels in wild males and females, suggesting a positive relationship between hormone levels and preen gland secretions, and a possible role for these secretions in signaling receptivity. In females, the greatest relative concentrations of most compounds were observed close to egg laying, a time when steroid hormones are high and also the only time that females respond to an injection of gonadotropin-releasing hormone with a short-term increase in T. In a study of captive juncos held on short days, we asked whether the seasonal increases observed in the wild could be induced with experimental elevation of T alone. We found that exogenous T stimulated the production of some volatile compounds in non-breeding individuals of both sexes. However, of the 15 compounds known to increase during the breeding season, only four showed an increase in relative concentration in birds that received T implants. Our results suggest that testosterone levels likely interact with other seasonally induced physiological changes to affect volatile compound amounts in preen oil.

Physiological and biochemical aspects of the avian uropygial gland / Aspectos fisiológicos e bioquímicos da glândula uropigial das aves

This review discusses different aspects of the uropygial gland of birds. The gland exhibits a striking morphological diversity in size, shape and presence/absence of tufts of feathers. It was shown that acidic mucins, neutral lipids, glycolipids and phospholipids are normal components of secretion. Several morphological and physiological aspects of the gland were studied on Rock Pigeon Columba livia Gmelin, 1879. The amount of the uropygial gland secretion, its lipid content and fatty acids profile were determined. The extracted lipid mixture contained of C14 to C20 fatty acids, mostly unsaturated; the saturated fatty acids were mainly 14:0, 16:0 and 18:0. No correlation was found between the size of the gland and the aquatic/terrestrial nature of the species. Ablation of the gland did not affect survival, body weight, feeding rate and serum cholesterol, total lipids or calcium levels after 32-120 days. The possible role of the gland in the protection against lipophilic compounds was discussed. The function of the gland is still a subject of controversy. It is accepted that its secretion confers water-repellent properties on the feather coat and maintain the suppleness of the feathers. Other physiological roles of the gland secretion may be associated to pheromone production, control of plumage hygiene, thermal insulation and defence against predators. Concerning the endocrine regulation of the uropygial function, there is scarce information presenting evidence for steroid regulated mechanisms.

Esta revisão discute diferentes aspectos da glândula uropigial das aves. A glândula exibe uma chamativa diversidade morfológica de tamanho, forma e presença/ausência de um tufo de penas. A glândula mostrou mucinas ácidas, lipídios neutros, glicolipídios e fosfolipídios como componentes normais de sua secreção. Diversos aspectos morfológicos e fisiológicos da glândula foram estudados na pomba doméstica Columba livia. Foi determinada a quantidade de secreção da glândula uropigial, seu conteúdo lipídico e o perfil de ácidos sebosos. A mistura lipídica extraída contém ácidos graxos C14 a C20, principalmente não saturados; os ácidos graxos saturados foram principalmente 14:0, 16:0 e 18:0. Não se encontrou correlação entre o tamanho da glândula e a natureza aquática/terrestre das espécies. A ablação da glândula não afetou a sobrevivência, peso corporal, alimentação e os níveis séricos de colesterol, lipídios totais ou cálcio depois de 32-120 dias. Discute-se o possível papel da glândula na proteção contra compostos lipofílicos. A função da glândula é ainda tema de controvérsia. Aceita-se que sua secreção confere às penas propriedades repelentes à água e as mantém flexíveis. Outras funções fisiológicas da secreção glandular podem estar associadas com a produção de feromonas, controle da higiene da plumagem, isolamento térmico e defesa contra predadores. Com relação à regulação endócrina da glândula, tem-se escassa informação, apresentando evidência de mecanismos de regulação de esteróides.