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Demodex folliculorum and brevis are commensal mites that live in low densities in human pilosebaceous follicles as part of the normal adult microbiota, but that give rise to demodicosis and, possibly, rosacea, when they proliferate excessively. This proliferation is favored by various factors, including age, marked immunosuppression, sebaceous gland hyperplasia, and hypervascularization-related factors. To study possible factors influencing mite proliferation, we explored the effects of different variables on Demodex densities (Dd) in a retrospective study of two groups of subjects selected on the basis of their clinical diagnosis: Demodex+, consisting of subjects with demodicosis or with centro-facial papulopustules suggesting rosacea (n = 844, mean Dd 263.5 ± 8.9 D/cm2 ), and Demodex-, consisting of subjects with other facial dermatoses or healthy facial skin (n = 200, mean Dd 2.3 ± 0.4 D/cm2 ). Demodex densities were measured using two consecutive standardized skin surface biopsies (SSSB1 [superficial] and SSSB2 [deep]) taken from the same facial site on each subject. In the Demodex+ group: the SSSB1 decreased with age in women (p = 0.004), and the SSSB2 increased with age in men (p = 0.001) (the pattern was similar for SSSB1 + 2, but not statistically significant); Dds were lower in those who had received cortisone (either topically or systemically); 13 subjects (1.5%) had known immunosuppression, 62 (7.3%) had hypothyroidism, and in 20 (3.6% of the women) there was a reported link with pregnancy; 78 of the subjects (9.2%) were part of a pair from the same family or household; when associated bacterial infection was suspected, Staphylococcus epidermidis was often isolated. Our results suggest close interactions between the mite, sebaceous gland size and function, and subtle variations of immune status. Potential factors influencing Demodex proliferation should be further investigated, including hypothyroidism, pregnancy, corticosteroid administration, Staphylococcus epidermidis, contagiousity, and genetic background.

Acne vulgaris, a chronic inflammatory skin disease, has been associated with not only sebaceous gland dysfunction but also various endogenous and exogenous stresses. Since sebaceous glands are under neuroendocrine control, including the hypothalamic-pituitary-adrenal axis and neuro-autocrine mechanisms, it remains unclear how psychological stress relates to the pathogenesis of acne. In this study, we investigated the relationship between psychological stress and catecholamine in acne lesions from 18 patients with mild or moderate acne. The State-Trait Anxiety Inventory (STAI) revealed that all patients were anxious, with six having low anxiety and 12 high anxiety. Salivary α-amylase activity (sAA), which is regulated by the sympatho-adrenal medullary (SAM) system, positively correlated with the STAI State Anxiety scores (STAI-S) and was significantly detectable in acne patients with high rather than low anxiety. In addition, the level of normetanephrine, but not metanephrine, both of which are catecholamine metabolites, in hair follicles of acne lesions also positively correlated with the STAI-S. Furthermore, the normetanephrine level was higher in patients with high rather than low anxiety, whereas there was no change in metanephrine in the hair follicles of the acne lesions. Moreover, neither the sAA nor metanephrine and normetanephrine in the acne lesions was related to acne severity in the patients. Thus, these results provide novel evidence that a SAM system-associated increase of normetanephrine level in hair follicles is involved in the acne pathology of patients with anxiety.

Transverse sectioning of skin biopsy specimens has revolutionised assessment of human alopecia by demonstration of every hair in each specimen, allowing quantitative evaluation of follicular activity. Since only vertical sectioning is performed routinely in veterinary laboratories, we aimed to determine whether transverse sectioning was a valuable technique in assessment of canine alopecia. Paired vertical and transverse sections of biopsy specimens from 31 alopecic dogs were examined independently in triplicate in random order and blinded to previous diagnosis using a standard check-list proforma. Assessments of key features (follicular activity [anagen/telogen], infundibular hyperkeratosis, sebaceous gland abnormalities, pigment clumping, dermal inflammation) by each sectioning method were compared. In the 31 cases, (atrophic [n = 13], dysplastic [n = 12], inflammatory diseases [n = 6]), follicular inactivity scores (median, [lower-upper quartile]) in transverse sections significantly exceeded those in vertical sections (transverse 4 [3-5], vertical 3 [2-4]). Agreement between the two sectioning planes was moderate for infundibular hyperkeratosis (kappa = 0.5210) and dermal inflammation (0.4351), fair for sebaceous gland abnormalities (0.3966) and pigment clumping (0.2197), but slight for follicular activity (0.1041). Vertical sectioning demonstrated diagnostically important epidermal pathology (n = 2) and dermal thinning (n = 3) whereas transverse sectioning enhanced assessment of hair growth phase (n = 11), follicular structure and architecture (n = 11), and focal luminal or mural folliculitides (n = 3). Transverse sectioning confers significant benefits and complements traditional vertical sectioning in the histological assessment of canine hair follicle diseases, particularly when subtle abnormalities comprise distorted compound follicle architecture, hair cycle arrest or when relatively few adnexal structures are affected. [Abstract copyright: © 2020 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.]

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

Background Excessive androgenesis in the skin promotes sebaceous hyperproduction which is the onset of acne vulgaris pathogenesis. Free fatty acids and lipid accumulation in the glandular infundibulum culminates in microbiota imbalance, triggering inflammatory response and follicular hyperkeratinization. Aims The purpose of this work was to present an alternative cosmetic treatment for acne skin care, focusing on the prevention of sebaceous gland dysregulation. Methods Insulin-stimulated human sebocytes were treated with noncytotoxic concentrations of a DTRW cosmetic formulation. After 6 days of incubation, cell lysates were collected for testosterone, 5α-reductase, and dyhidrotestosterone (DHT) quantitation. In parallel, cells were stained with Oil Red O to measure sebum production. Results Human sebocytes were incubated with insulin to mimic a seborrheic microenvironment with overproduction of intracellular lipids and fatty acids. Concomitant incubation of cell cultures with DRTW was able to promote a 52.97% reduction in intracellular lipid content. The anti-androgenic properties of DRTW had been proved by the reductions of testosterone (↓59.90%), 5α reductase (↓59.34%), and DHT (↓55.98%) levels in sebocyte cultures also stimulated with insulin. Conclusion The results indicate a promising action of DRTW cosmetic formulation in preventing the development of acne lesions by mechanisms involving the modulation of cutaneous androgenesis and consequently the control of sebum overproduction, considered one of the leading causes of acne.

The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

Background and objectives The selective electrothermolysis of the sebaceous glands was suggested as a novel therapeutic option for facial acne. However, there has been no randomized controlled trial to evaluate the effectiveness and safety of the monopolar radiofrequency (RF) device using single microneedle with proximal insulation. The objective of the study was to evaluate the efficacy and tolerability of intralesional electrothermolysis using monopolar RF device and proximally-insulated single microneedle in acne patients. Study design/materials and methods The prospective randomized controlled clinical trial was performed to treat moderate-to-severe facial acne. Subjects randomized to the treatment group received three treatments at 4-week intervals with an RF device, whereas the control group received micro-needling and extraction. For efficacy evaluation, reduction rate of acne lesions were evaluated by two independent physicians. Results Sixty-three patients completed the study and the results showed statistically significant improvement of inflammatory acne at 12 weeks. The number of inflammatory lesions was significantly reduced at 12 weeks (20.86 vs. -5.13; P = 0.03) compared with controls. Conclusions Selective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent improvement in acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The histogenesis of extraocular sebaceous carcinomas is - in contrast to ocular sebaceous carcinomas - unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki-67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63+ K5+ progenitors which generate the K10+ luminal cells of sebaceous ducts; and (ii) p63+ K5+ K7+ progenitors which finally generate K7+ adipophilin+ EMA+ sebocytes. Without exception, all types of sebaceous tumors contained p63+ K5+ cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin+ and/or EMA+ mature sebocytes and to K10+ ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63+ K5+ cells play a major role.

Skin becomes the largest organ in the body and protects its own inner layer. The structure and chemical composition of the skin contribute to skin condition and affect the habitat of certain bacteria. The Sunda Porcupine is one of endemic animals of Indonesia which possesses quill as the main derivate of its skin and as a defence tool against predators. The present study used nine adults (five females and four males) of Sunda Porcupine and aimed to observe the correlation of skin structure with bacterial population at the surface level. The skin was wavy due to the protrusion of quill follicle orifices on the skin surface and formed clusters. The skin of Sunda Porcupine was also wrinkled and had a lot of flakiness. Histologically, the skin was composed of epidermis, dermis, hypodermis and subcutaneous muscle. The quill follicles and their properties were the dominant structure component of the skin. No sweat gland was observed in the skin of the Sunda Porcupine, and sebaceous gland was found only around quill and hair follicles. The bacterias identified in the skin were Staphylococcus aureus, S. epidermidis, Micrococcus sp. and Salmonella sp. When compared, the bacterial population was higher in the lumbosacral region than in the thoracodorsal region, but the difference was not significant. The density of quill clusters was negatively correlated to the bacterial population. It was suggested the structure of the skin has contribution to bacterial population in dorsal trunk of the Sunda Porcupine.

We have reported recently that inactivation of the essential autophagy-related gene 7 (Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, (Atg7 ΔKC), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP-LC3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 ΔKC mice compared to those of controls (Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age-matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids (FFA) and cholesterol, and a 5-fold increase in the proportion of fatty acid methyl esters (FAME). In addition, the most common diester wax species (58-60 carbon atoms) were increased, while shorter species (54-55 carbon atoms) were under-represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.

Recognised for its key role in lactation, it is less well appreciated that the neurohormone prolactin (PRL) is actually one of the most pleiotropic hormones known. Not only does PRL exert both tropic and trophic effects in a wide range of tissues, but it is also expressed in human skin and hair follicles and regulates multiple complex cutaneous functions, including keratin expression and hair growth. Despite several clinical indications that PRL may also play a role in sebaceous gland (SG) biology, the effects of PRL on SG function have received little attention. In this Viewpoint essay, we argue that PRL may be a sebotrop(h)ic hormone and could represent a novel therapeutic target in human dermatoses affecting the SG. We provide preliminary evidence in support of this hypothesis (based on findings in human skin organ culture) and chart the major open questions in SG biology and pathology from a PRL research perspective. We close by delineating how these questions can be experimentally addressed so as to identify new therapeutic strategies that are either sebogenic or sebostatic, for example in the management of acne and cutaneous ageing.

Intracranial epidermoid cysts are rarely known to increase in size over a brief period. While malignant transformations of epidermoid cyst have been previously described, no reports to date have described rapid proliferation accompanied by mature hair follicles and sebaceous glands without malignant transformations. The present case involved a 71-year-old man who visited a local physician with disturbance of equilibrium. A mass lesion was detected at the left cerebellopontine angle and was subsequently removed. Histopathological diagnosis of this lesion was as an epidermoid cyst. Seventeen years after this initial surgery, worsened left hypoacusis, disorientation, eating disorder and gait disturbance appeared, and the patient visited the physician again. Local recurrence of the lesion was observed, and the patient was referred to our hospital for its removal. Intraoperative findings revealed a pearly white tumor, histopathologically diagnosed as an epidermoid cyst. Three years later, local recurrence was observed, and the cyst was again removed. Intraoperative findings revealed a partially pearly white tumor similar to the tumor observed during the second surgery, but the majority of the tumor was non-shiny, ochre-colored and suckable. Histopathological diagnosis was an epidermoid cyst with an epidermis-like structure. Postoperative activities of daily living were independent thereafter, but from March of the following year, he began to experience increasing difficulty in walking and subsequently visited our hospital again. Tumor recurrence was observed and was removed again in November of the same year. Intraoperative findings revealed a tumor that was primarily ochre-colored, non-shiny, brittle and suckable. The histopathological diagnosis was folliculosebaceous epithelial proliferative lesion accompanied by an epidermis-like epithelium and a differentiation into hair follicles and sebaceous gland,s and the tumor was determined to be an epidermoid cyst with proliferative folliculosebaceous epithelium.

Acne is a chronic inflammatory disease of the pilosebaceous unit. Its pathophysiology includes hyperseborrhoea, abnormal follicular keratinization and Propionibacterium acnes proliferation in the pilosebaceous unit. Recent research has shed some new light on the involvement of the sebaceous gland, as well as on the pro-inflammatory activity of the cutaneous microbiome. During puberty, alteration of the sebaceous lipid profile, called dysseborrhoea, stress, irritation, cosmetics and potential dietary factors lead to inflammation and formation of different types of acne lesions. Dysbiosis, the process leading to a disturbed skin barrier and disequilibrium of the cutaneous microbiome, resulting in the proliferation of P. acnes strains, is another important process that triggers acne. P. acnes activates the innate immunity via the expression of protease activated receptors (PARs), tumour necrosis factor (TNF) α and toll-like receptors (TLRs), and the production of interferon (INF) γ, interleukins (IL-8, IL12, IL-1), TNF, and matrix metalloproteinases (MMPs) by keratinocytes, resulting in the hyperkeratinization of the pilosebaceous unit. Rebalancing the natural microbiome of the skin by restoring the natural skin barrier, limiting the proliferation of P. acnes on the skin by using topical antibacterials which do not cause resistance and regulating quantity and quality of sebum will be the main acne treatment challenges in the future. The aim of this article to provide an update on the involvement of the sebaceous gland, the innate immunity and the cutaneous microbiome, how all of these factors promote acne and to illustrate their links with current and future treatments.

Some dogs with chronic otitis externa (OE) develop proliferation of the tissues surrounding the opening of the external ear canal, resulting in obstruction. Traditionally total ear canal ablation with bulla osteotomy (TECABO) has been recommended.To evaluate the efficacy of a novel treatment using carbon dioxide (COTwenty-six dogs were included, 16 with bilateral and 10 with unilateral disease (42 ears were treated). Dogs with nonpatent horizontal ear canal or macroscopic calcification of the ear canal were excluded. For histopathological evaluation, tissue samples were collected from 11 dogs (17 ears).Hyperplastic tissue around the canal opening and within the vertical ear canal was dissected and ablated using a COFollowing COCarbon dioxide laser surgery is an effective treatment of proliferative OE causing obstruction of the ear canal opening and vertical canal, and should be considered as an alternative to TECABO whenever possible.Des chiens avec otite externe chronique (OE) développent des proliférations des tissus entourant l’ouverture du conduit auriculaire externe résultant en une obstruction. Une ablation totale du conduit auriculaire avec ostéotomie (TECABO) est traditionnellement recommandée.Evaluer l’efficacité d’un nouveau traitement utilisant la chirurgie laser au dioxide de carbone (CO2) et décrire les données histopathologiques de l’OE obstructive et proliférative chronique.Vingt-six chiens ont été inclus, 16 avec atteinte bilatérale et 10 avec atteinte unilatérale (42 oreilles ont été traitées). Les chiens avec canal horizontal lésé ou calcification macroscopique du conduit auriculaire ont été exclus. Pour analyse histopathologique, des échantillons cutanés ont été prélevés sur 11 chiens (17 oreilles). MATÉRIELS ET METHODS: Le tissu hyperplasique bordant l’ouverture des conduits auriculaires et au niveau du conduit vertical a été disséqué et retiré à l’aide d’un laser au CO2. Les échantillons de biopsies ont été évalués pour l’hyperplasie des glandes cérumineuses et sébacées, hyperplasie épidermique, inflammation et fibrose. RÉSULTATS: A la suite de la chirurgie au laser à CO2, il y avait une évolution bonne à excellente avec résolution des proliférations pour 39 des 42 oreilles de 24 des 26 chiens. Un suivi était suffisant pour 21 chiens et trois chiens ont eu deux chirurgies. Deux chiens ont récidivé après une chirurgie et ont subi une TECABO. Deux chiens n’ont pas eu de récidive de prolifération tissulaire après chirurgie et ont eu une infection persistante et ont subi une TECABO. Les autres chiens ont été traités médicalement au long cours à la suite de la chirurgie. A l’histopathologie, huit oreilles avaient une réaction des glandes sébacées prédominante, trois avaient une réponse principalement des glandes cérumineuses et six avaient un patron glandulaire mixte. L’hyperplasie épidermique, l’inflammation et la fibrose variaient de moyennes à sévères.La chirurgie au laser Co2 est un traitement efficace de l’OE proliférative entrainant une obstruction du conduit auriculaire et du canal vertical et devrait être considéré en alternative à la TECABO lorsque possible.INTRODUCCIÓN: algunos perros con otitis externa crónica (OE) desarrollan proliferación de los tejidos que rodean la apertura del canal auditivo externo, lo que provoca una obstrucción. Tradicionalmente se ha recomendado la ablación total del canal auditivo con osteotomía de bulla (TECABO). OBJETIVOS: Evaluar la eficacia de un tratamiento novedoso mediante la cirugía con láser de dióxido de carbono (CO2) y describir las características histopatológicas de la OE crónica proliferativa y obstructiva. ANIMALES: Se incluyeron veintiséis perros, 16 con enfermedad bilateral y 10 con enfermedad unilateral (se trataron 42 orejas). Se excluyeron los perros con conducto auditivo horizontal no patente o con calcificación macroscópica del conducto auditivo. Para la evaluación histopatológica, se recolectaron muestras de tejido de 11 perros (17 orejas). MÉTODOS Y MATERIALES: el tejido hiperplásico alrededor de la abertura del canal y dentro del canal auditivo vertical se diseccionó y extirpó con un láser de CO2. Las muestras de biopsia se evaluaron prestando atención a la hiperplasia de las glándulas sebáceas y ceruminosas, hiperplasia epidérmica, inflamación y fibrosis. RESULTADOS: después de la cirugía con láser de CO2 hubo un resultado bueno o excelente con una resolución sustancial de los cambios proliferativos en 39 de 42 oídos de 24 de 26 perros. Una cirugía fue suficiente en 21 perros y tres perros tuvieron dos cirugías. Dos perros tuvieron recidiva de tejido proliferativo después de una cirugía y se sometieron a TECABO. Dos perros no tuvieron recidiva del tejido proliferativo después de la cirugía, pero tuvieron una infección luminal persistente y se sometieron a TECABO. El resto de los perros fue tratado médicamente de manera efectiva a largo plazo después de la cirugía. Histológicamente, ocho oídos tuvieron una respuesta predominantemente de las glándulas sebáceas, tres tuvieron una respuesta predominantemente ceruminosa y seis tuvieron un patrón glandular mixto. La hiperplasia epidérmica, la inflamación y la fibrosis variaron de leves a graves. CONCLUSIONES Y RELEVANCIA CLÍNICA: La cirugía con láser de CO2 es un tratamiento eficaz de la OE proliferativa que causa obstrucción de la apertura del canal auditivo y del canal vertical, y debe considerarse como una alternativa a TECABO siempre que sea posible.Einige Hunde mit einer chronischen Otitis Externa (OE) entwickeln eine Proliferation der Gewebe, die die Öffnung des äußeren Gehörgangs umgeben, was in einer Obstruktion endet. Traditionellerweise wurde dann eine totale Ohrkanalablation mit einer Bulla Osteotomie (TECABO) empfohlen.Eine Evaluierung der Wirksamkeit einer neuen Behandlung mittels Carbondioxid (Co2) Laser Chirurgie und die Beschreibung der histopathologischen Merkmale chronisch proliferativer obstruktiver OE.Es wurden sechsundzwanzig Hunde in die Studie aufgenommen, 16 mit bilateraler und 10 mit unilateraler Erkrankung (42 Ohren wurden behandelt). Hunde mit nicht durchgängigem horizontalem Ohrkanal oder makroskopisch sichtbarer Kalzifizierung des Ohrkanals wurden ausgeschlossen. Es wurden Gewebeproben von 11 Hunden (17 Ohren) zur histopathologischen Untersuchung entnommen.Das hyperplastische Gewebe rundum die Öffnung des Ohrkanals sowie innerhalb des vertikalen Ohrkanals wurde herausgeschnitten und mittels CO2 Laser abgetragen. Biopsieproben wurden auf eine Hyperplasie im Bezug auf Talgdrüsen sowie der ceruminösen Drüsen, auf eine epidermale Hyperplasie, Entzündung und Fibrose evaluiert.Nach der CO2 Laser Chirurgie ergab sich ein gutes bis exzellentes Ergebnis mit deutlicher Verbesserung der proliferativen Veränderungen bei 39 der 42 Ohren von 24 der 26 Hunde. Ein chirurgischer Eingriff war bei 21 Hunden ausreichend und drei Hunde hatten zwei Operationen. Bei zwei Hunden trat das proliferative Gewebe nach einer Operation wieder auf und es wurde eine TECABO durchgeführt. Bei zwei Hunden ergab sich kein Wiederauftreten des proliferativen Gewebes nach der Operation, allerdings hatten sie eine ständige luminale Infektion und so wurde auch eine TECABO durchgeführt. Die übrigen Hunde wurden nach der Operation langfristig mit Medikamenten erfolgreich gemanagt. Histologisch zeigten acht Ohren hauptsächlich eine Reaktion der Talgdrüsen, drei zeigten hauptsächlich eine Reaktion der ceruminösen Drüsen und sechs hatten eine gemischt drüsige Reaktion. Das Ausmaß der epidermalen Hyperplasie, der Entzündung und Fibrose reichte von mild bis gravierend.Die CO2 Laser Chirurgie ist eine wirksame Behandlung der proliferativen OE, welche eine Obstruktion der Öffnung des Ohrkanals und des Vertikalkanals verursacht, und sollte als Alternative zur TECABO wenn nur irgend möglich in Betracht gezogen werden.背景: 慢性外耳炎の犬の中には、外耳道の開口部周辺の組織が増殖し、閉塞をきたす症例がいる。従来、全耳道切除および鼓室胞骨切り術(TECABO) が推奨されてきた。 目的: 本研究の目的は、二酸化炭素 (CO2) レーザー手術を用いた新しい治療法の有効性を評価し、慢性増殖性および閉塞性OEの病理組織学的特徴を説明することであった。 供試動物: 26頭の犬が対象となり、両側性疾患が16頭、片側性疾患が10頭であった (42の耳が治療された) 。閉塞性の水平耳道や外耳道に巨視的石灰化のある犬は除外した。病理組織学的評価のために、11頭 (17耳) の犬から組織サンプルを採取した。 材料と方法: 外耳道開口部周辺および垂直耳道内の過形成組織を切開し、CO2レーザーを用いて切除した。生検サンプルは、皮脂腺・耳垢腺過形成、表皮過形成、炎症、線維化を評価した。 結果: CO2レーザー手術後、26頭中24頭の42耳中39耳で増殖性変化が実質的に消失し、良好または優れた結果が得られた。21頭の犬は1回の手術で十分であり、3頭は2回の手術を受けた。2頭は1回の手術で増殖組織が再発し、TECABOを実施した。2頭は手術後に増殖組織の再発はなかったが、腔内感染が持続したためTECABOを実施した。残りの犬は手術後、長期にわたって効果的な内科的管理を受けた。組織学的には、8頭の耳が主に皮脂腺反応を示し、3頭が主に耳垢腺反応を示し、6頭が混合腺パターンを示した。表皮過形成、炎症、線維化は軽度から重度まで様々であった。 結論と臨床的妥当性: CO2レーザー手術は、外耳道開口部および垂直耳道の閉塞を引き起こす増殖性OEの有効な治療法であり、可能な限りTECABOの代替として考慮されるべきである。.背景: 一些慢性外耳炎(OE)患犬存在耳道开口周围组织增生, 导致阻塞。传统上推荐采用骨泡截骨术(TECABO)进行全耳道消融。 目的: 评价使用二氧化碳(CO2)激光手术的新型治疗的疗效, 并描述慢性增生性和阻塞性OE的组织病理学特征。 动物: 纳入了26只犬, 16只为双侧, 10只为单侧发病 (治疗了42个耳道) 。排除水平耳道不通畅或耳道肉眼可见钙化的犬。从11只犬 (17个耳道) 中采集组织样本进行组织病理学评价。 方法和材料: 使用CO2激光切除和和消融耳道开口周围和垂直耳道内的增生组织。评价活检样本的皮脂腺和耵聍腺增生、表皮增生、炎症和纤维化。 结果: CO2激光手术后, 26只犬中的24只的42个耳道中, 有39个的增生性变化显著消退, 结果良好或极佳。21只犬1次手术足矣, 3只犬2次手术。2只犬1次手术后增殖组织复发, 进行TECABO。2只犬术后增殖组织无复发, 但耳道内持续感染, 进行TECABO。其余犬在术后接受了有效的长期药物治疗。组织学上, 8个耳道以皮脂腺反应为主, 3个以耵聍腺反应为主, 而6个呈混合腺体模式。表皮增生、炎症和纤维化从轻度到重度不等。 结论和临床相关性: 对于耳道开口和垂直耳道阻塞的增生性OE,CO2激光手术是有效治疗方法, 应尽可能考虑作为TECABO的替代疗法。.Alguns cães com otite externa (OE) crônica desenvolvem proliferação dos tecidos no entorno da abertura do conduto auditivo externo, resultando em obstrução. Tradicionalmente, a ablação total do conduto auditivo com osteotomia de bulha (TECABO) tem sido recomendada.Avaliar a eficácia de um novo tratamento utilizando cirurgia a laser de dióxido de carbono (COVinte e seis cães foram incluídos, 16 com doença bilateral e 10 unilateral (42 orelhas foram tratadas). Cães com conduto auditivo horizontal não patente ou calcificação macroscópica do conduto auditivo foram excluídos. Para avaliação histopatológica, foram coletadas amostras de tecido de 11 cães (17 orelhas). MÉTODOS E MATERIAIS: O tecido hiperplásico ao redor da abertura do condutol e dentro do conduto auditivo vertical foi dissecado e ablado com laser de COApós a cirurgia com laser de CO

To explore the role of amphiregulin in inflammatory epidermal hyperplasia, we overexpressed human AREG (hAREG) in FVB/N mice using a bovine K5 promoter. A construct containing AREG coding sequences flanked by 5' and 3' untranslated region sequences (AREG-UTR) led to a >10-fold increase in hAREG expression compared to an otherwise-identical construct containing only the coding region (AREG-CDR). AREG-UTR mice developed tousled, greasy fur as well as elongated nails and thickened, erythematous tail skin. No such phenotype was evident in AREG-CDR mice. Histologically, AREG-UTR mice presented with marked epidermal hyperplasia of tail skin (2.1-fold increase in epidermal thickness with a 9.5-fold increase in Ki-67(+) cells) accompanied by significantly increased CD4+ T-cell infiltration. Dorsal skin of AREG-UTR mice manifested lesser but still significant increases in epidermal thickness and keratinocyte hyperplasia. AREG-UTR mice also developed marked and significant sebaceous gland enlargement, with corresponding increases in Ki-67(+) cells. To determine the response of AREG-UTR animals to a pro-inflammatory skin challenge, topical imiquimod (IMQ) or vehicle cream was applied to dorsal and tail skin. IMQ increased dorsal skin thickness similarly in both AREG-UTR and wild type mice (1.7- and 2.2-fold vs vehicle, P < 0.001 each), but had no such effect on tail skin. These results confirm that keratinocyte expression of hAREG elicits inflammatory epidermal hyperplasia, and are consistent with prior reports of tail epidermal hyperplasia and increased sebaceous gland size in mice expressing human epigen.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll-like receptor (TLR)2 and 4 activators], or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.

Summary Ectopic sebaceous glands (ESGs) are benign esophageal lesions that have a lower detection rate than malignant lesions because most patients are asymptomatic. However, this rate can be increased by the widespread use of endoscopes and an increasing awareness of the disease. Through esophagogastroduodenoscopy, ESGs often appear in the middle and lower esophagus in numbers ranging from 1 to more than 100 yellowish plaques measuring 1–2 mm in diameter. Histopathological examination of ESGs would reveal small lobular cluster glands in the lamina propria. Diagnosis is usually confirmed through an endoscopic biopsy. ESGs are best distinguished from other yellowish lesions such as xanthoma via endoscopy. These lesions tend to appear singly scattered, whereas xanthomas tend to be clustered. We present three cases of ESGs in the esophagus. Although their etiologies are still unclear, we present related theories in our review.

The mechanism of formation of facial wrinkles has not been fully clarified due to the existence of many distinct influential factors. To clarify the relationship between facial wrinkles and structures in the skin, especially sebaceous glands, image analysis was performed on the forehead and lateral canthus regions of cadaveric skin specimens; 58 male and female donated cadavers (age range at death 20s - 90 s) were included in the study. Specimens were obtained from forehead and lateral canthus region after measuring wrinkle depth. Then tissue slices were prepared to observe the sebaceous gland and its density was measured and analyzed in relation to wrinkle depth, retinacula cutis density, dermal thickness, and solar elastosis degree. A correlation was found between sebaceous gland density and wrinkle depth in forehead specimens with a lower retinacula cutis density. Wrinkles were shallower in specimens with a higher sebaceous gland density. However, no such correlation was found in lateral canthus wrinkles, presumably due to the lack of sebaceous glands in that region. In addition, specimens with a higher sebaceous gland density tended to have a thicker dermis and/or less solar elastosis. Sebaceous gland density seems to be one of the multiple factors that prevent wrinkle deepening, and that is why wrinkles are deeper in the lateral canthus area than in the forehead. Functional studies will elucidate the mechanism of wrinkle formation in the future.

The sebaceous gland displays key functions of the human skin, such as hormone synthesis in situ, antimicrobial activity and participation to inflammatory responses. Consequently, there is an emerging need of advanced in vitro models to study complex interactions between the sebaceous gland and the other skin compartments. Despite the evolution of both full-skin organ culture and reconstructed three-dimensional skin models, no satisfactory solutions have been provided for the integration of sebaceous glands and/or sebaceous gland cells in those models, probably due to their problematic maintenance both in vitro and ex vivo. We have developed a coculture model of explant skin in direct contact with immortalized SZ95 sebocytes, which resulted in overall improved structural integrity of the epidermis, higher percentage of proliferating basal epidermal cells and reduced apoptosis of differentiating keratinocytes after 6 days, as detected by Ki67 and TUNEL staining, respectively. Furthermore SZ95 sebocytes exhibited morphological and biochemical signs of normal differentiation and lipid accumulation, while interleukin-6 expression in the supernatant of the cocultures was decreased in comparison with the control. The data provide evidence of a beneficial interaction between sebocytes and skin explants and provide the rationale for their integration in future three-dimensional skin models.

The roles of the epidermal growth factor receptor (EGFR) in sebaceous glands remain poorly explored. We show that human sebocytes express EGFR and lower levels of ERBB2 and ERBB3, all receptors being downregulated after the induction of lipid synthesis. Nile red staining showed that siRNA-mediated downregulation of EGFR or ERBB3 increases lipid accumulation, whereas ERBB2 downregulation has no effect. Spectrometry confirmed induction of triglycerides after EGFR or ERBB3 downregulation and revealed induction of cholesteryl esters after downregulation of EGFR, ERBB2 or ERBB3. Thus, EGFR/ERBB receptors differentially modulate sebaceous lipogenesis, a key feature of sebaceous gland physiology and of several skin diseases.

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.

A review of the oxidization of squalene, a specific human compound produced by the sebaceous gland, is proposed. Such chemical transformation induces important consequences at various levels. Squalene by-products, mostly under peroxidized forms, lead to comedogenesis, contribute to the development of inflammatory acne and possibly modify the skin relief (wrinkling). Experimental conditions of oxidation and/or photo-oxidation mechanisms are exposed, suggesting that they could possibly be bio-markers of atmospheric pollution upon skin. Ozone, long UVA rays, cigarette smoke… are shown powerful oxidizing agents of squalene. Some in vitro, ex vivo and in vivo testings are proposed as examples, aiming at studying ingredients or products capable of boosting or counteracting such chemical changes that, globally, bring adverse effects to various cutaneous compartments.

Sebaceous gland hyperplasia (SGH) is a benign cutaneous condition that presents primarily on the face and increases with UVB exposure and ageing. These lesions are a common cosmetic concern but are difficult to treat, as the entire sebaceous gland needs to be destroyed to prevent recurrence. Traditional methods of treatment include: cryosurgery, electrodessication, curettage, shave excision and topical trichloroacetic acid. These methods have an increased risk of skin discoloration and scarring to the area of treatment that may lead to inferior cosmetic outcomes. Alternatively, oral isotretinoin can treat SGH, but is a known teratogen in pregnancy and has high relapse rates with discontinuation. A systematic review of the literature was performed to look at photodynamic therapy (PDT) and laser treatment for SGH. According to the results of this study, PDT, lasers and combinations of the two treatments were found to offer alternatives to the more conventional techniques with better outcomes. In particular, the use of wavelength-specific laser for the sebaceous gland of 1720 nm were found to have better outcomes and provide minimal damage to surrounding tissues. Additionally, combination PDT with aminolevulinic acid and pre-treatment with carbon dioxide laser ablation or pulse-dyed laser offered higher cure rates over stand-alone laser or PDT treatments in a shorter number of sessions with similar transient side-effects. However, further large-scale prospective studies with adequate follow-up are required to confirm these findings and those for sebaceous gland-specific lasers.

Acne vulgaris (acne) is a chronic inflammatory disease of the sebaceous gland, characterized by follicular hyperkeratinization, excessive colonization by Propionibacterium acnes (P. acnes) as well as immune reactions and inflammation. Despite an armamentarium of topical treatments available including benzoyl peroxide, retinoids and azelaic acid, topical antibiotics in monotherapies, especially erythromycin and clindamycin, are still used in Europe to treat acne. This intensive use led to antimicrobial-resistant P. acnes and staphylococci strains becoming one of the main health issues worldwide. This is an update on the current topical acne treatments available in Europe, their mechanism of action, their potential to induce antimicrobial resistance and their clinical efficacy and safety.

Distinct mutations in the gap junction protein connexin30 (Cx30) can cause the ectodermal dysplasia Clouston syndrome in humans. We have generated a new mouse line expressing the Clouston syndrome mutation Cx30A88V under the control of the endogenous Cx30 promoter. Our results show that the mutated Cx30A88V protein is incorporated in gap junctional plaques of the epidermis. Homozygous Cx30A88V mice reveal hyperproliferative and enlarged sebaceous glands as well as a mild palmoplantar hyperkeratosis. Additionally, homozygous mutant mice show an altered hearing profile compared to control mice. We conclude that the Cx30A88V mutation triggers hyperproliferation in the skin and changes the cochlear homeostasis in mice.

Background Although the pathophysiology of acne vulgaris (AV) is not clear, androgens are thought to play an important role in its development through either an increased level of circulating androgens or end-organ sensitivity. The ratio of the length of the second and fourth digit (2D : 4D) has been hypothesized to reflect prenatal androgen exposure and/or an individual's sensitivity to androgens, with a low 2D : 4D ratio suggesting high prenatal androgen exposure. Interestingly, the prenatal androgen peak time period coincides with both the development of the sebaceous gland and digits. Objectives To determine the relationship between digit ratio and AV. Methods Vernier caliper was used to take digit measurements of both patients and controls. Acne severity was assessed by using the International Consensus Conference on Acne Classification System. Results Data of 251 patients with AV (67.7% female) and 120 healthy controls (72.5% female), aged 16–40 years, were analysed. The 2D : 4D ratios of female patients with AV were significantly lower than healthy females in both hands. However, there was no significant difference between male acne cases and controls. Acne severity was positively correlated with the left 2D : 4D ratios and mean 2D : 4D ratio, whereas the duration of acne was negatively correlated with the right 2D : 4D ratios in females. Conclusion Our results support the anatomical evidence of in utero androgen exposure and/or an individual's sensitivity to androgens in patients with AV and suggest that the 2D : 4D ratio might be a predictor of acne development, duration, and severity grade, at least in female patients.

Background/Objectives Alopecia areata (AA) is a non-scarring inflammatory hair loss disease. We investigated the early pathological changes of AA to identify possible factors participating in its pathogenesis. Methods Clinical, laboratory and pathological features of 87 AA patients were investigated. Results Anti-nuclear antibody was found in 11 of 85 patients tested (13%), with a higher percentage in women (21%) than men (5%) (P = 0.026). In early AA lesions, inflammatory infiltration in the upper dermis and epithelial cell damage of the hair follicle infundibulum, just above the sebaceous gland, was observed. Liquefaction and disarrangement of peripheral infundibular epithelial cells coexisted with T-lymphocytic invasion and regression of the lower follicle. The latter findings positively correlated with the presence of eosinophils and perivascular mononuclear cell infiltration in the upper dermis. Eosinophilic infiltration was found in 35 patients (40%) and was positively correlated to elevated serum IgE levels (r = 0.21, P = 0.044), a more severe perivascular lymphocytic inflammation in the upper dermis (r = 0.24, P = 0.026), as well as a prominent swarm of bees-like peri-follicular infiltration (r = 0.41, P

Sebaceous adenitis, an idiopathic inflammation of the sebaceous gland, is a condition that is well described in animals but has been reported only thrice previously in humans. We present a series of 11 cases of sebaceous adenitis that presented as tender nodular lesions clinically similar to hidradenitis suppurativa, but was confined to the labia minora. All cases responded to tetracyclines and anti-androgen therapy.

With 30 years of clinical use, it is appropriate to review the use of isotretinoin. We now understand that retinoids influence cellular growth, differentiation, morphogenesis and apoptosis, inhibit tumour promotion and malignant cell growth, exert immuno-modulatory actions and alter cellular cohesiveness. This has expanded the indications of isotretinoin from just acne and rosacea to a wide range of inflammatory and malignant skin disorders. While the standard dose of 0.5 to 1 mg/kg per day for 4 months to a cumulative dose of 120-140 mg/kg per day has served us well in the management of acne vulgaris, there is emerging evidence that much lower dosages (as low as 5 mg/day) are just as effective but have significantly fewer adverse effects. Relapse of acne vulgaris continues to be a problem but we are beginning to recognise that this is related less to the cumulative dose and more to the length of sebaceous gland suppression. Other factors important for relapse include a macrocomedonal pattern of acne, smoking and age, both younger (under 14 years) and older (over 25 years). After 30 years of use, we now understand why isotretinoin is such an effective drug. Not only does it clear acne in almost all patients, long-term remission can be achieved in 70-80% of patients with a single course. Important changes in the use of isotretinoin include using a lower daily dose for a longer period of time. New indications continue to emerge, particularly as a potential treatment for both intrinsic and extrinsic (photo) aging. Teratogenicity however, remains a very significant concern.

Fatty acid binding proteins (FABPs) are capable of binding long-chain FA and are involved in intracellular FA transport and signal transduction. In sebaceous glands, FABP5 is highly expressed in differentiated sebocytes; though, its function remains unclear. In this study, we examined the role of FABP5 in sebocytes using FABP5-deficient mice. The size of sebaceous glands was significantly reduced, while the sebum volume was increased with altered lipid composition in FABP5-deficient mice. However, no significant differences were discerned in the expression of proliferation or differentiation markers including Blimp1, c-myc, Ki67 and peroxisome proliferator-activated receptors (PPAR)γ between wild-type and FABP5-deficient sebaceous glands. The expression of cellular retinoic acid binding protein-2 (CRABP2) that is a competitor of FABP5 for RA signalling was increased in FABP5-deficient mice. These results suggest that FABP5 is involved in the regulation of sebaceous gland activity through modulation of cellular lipid signalling and/or metabolism in the sebocytes.

Background The aim of this study was to identify new target proteins in sebaceous gland carcinoma. Methods A tissue microarray containing 115 core biopsies was constructed and stained for proteins involved in carcinogenesis, angiogenesis, inflammation, and cell-to-cell contact. Two investigators independently determined protein expression of all antibodies. Results Vascular endothelial growth factor receptor 2 (VEGFR-2), platelet-derived growth factor receptor alpha and beta (PDGFR-α/-β), epidermal growth factor receptor (EGFR), cyclooxygenase 1 and 2 (Cox-1/-2), myeloid cell leukemia sequence 1 (Mcl-1), matrix metalloproteinase 1 (MMP-1), CD9, Bmi-1, 14-3-3σ, glutathione S-transferase pi (Gstπ), and members of the sonic hedgehog (SHH), AKT, and WNT pathways were significantly overexpressed in sebaceous gland carcinomas. Conclusions We have demonstrated for the first time that proteins related to angiogenesis, inflammation, and cell proliferation are overexpressed in sebaceous gland carcinomas. These proteins may hold promise as novel therapeutic targets for the treatment of sebaceous gland carcinoma. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Acne vulgaris is characteristic of excess sebum production and the induction of inflammatory reactions, for example, the augmentation of cytokine, prostaglandin (PG) and matrix metalloproteinase (MMP) production in sebaceous glands and pilosebaceous units. As Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, antimicrobial agents have been found to be effective for treating acne leading to the remission of inflammation. However, it is not fully understood whether antimicrobial agents influence sebum production and/or the inflammatory reactions in sebaceous gland cells (sebocytes). In the present study, topical antimicrobial agents such as nadifloxacin (NDFX) and clindamycin (CLDM) decreased the production of triacylglycerols (TG), which are a major component of sebum in insulin-differentiated hamster sebocytes. These antibiotics also suppressed insulin-augmented gene expression and the production of perilipin, by which intracellular lipid droplet formation was concomitantly inhibited. On the other hand, peptidoglycan (PGN) from Gram-positive bacteria dose-dependently increased TG production in hamster sebocytes. The augmented TG production was decreased by treating NDFX or CLDM. Furthermore, NDFX and CLDM inhibited the PGN-augmented PGE(2) production in the sebocytes. Moreover, NDFX, but not CLDM, suppressed the PGN-augmented gene expression and production of pro-MMP-2/progelatinase A in hamster sebocytes. Therefore, these results provide novel evidence that NDFX and CLDM exhibit anti-lipogenesis and anti-inflammatory activities against insulin- or PGN-activated sebocytes which at least partly mimic acne pathology in vitro. Moreover, NDFX for acne therapy is likely to be effective in not only inhibiting microbial proliferation but also in preventing the onset of acne scar formation.

Although many therapeutic options exist for acne, relapse often occurs after treatment is stopped. Some preliminary evidence suggests that selective electrothermolysis of the sebaceous glands may represent a novel therapeutic intervention. This trial was conducted to evaluate the efficacy and tolerability of selective sebaceous gland electrothermolysis for the treatment of facial acne. Twelve patients with facial acne were enrolled, all of whom underwent three sessions of therapy. During each session, a 1.5-mm long needle with 0.45-mm of base insulation was inserted into pores of acne lesions. Upon insertion, a high-frequency electrical current was applied for 0.25-0.50 seconds, for a total output of 40 W. Each treatment session took approximately 30-60 minutes. Subject response to therapy was evaluated at one month and 12 months after the final treatment. All the enrolled subjects completed the study and all reported satisfaction with treatment results. In all cases, a reduction in inflammatory and noninflammatory lesion counts was observed after three sessions of selective electrothermolysis, although a few small papules and comedones persisted in several areas of untreated facial skin. Mean lesion reduction at one month after the final treatment was 98.14% for inflammatory lesions and 83.09% for noninflammatory lesions. Clinical success was achieved in the majority of patients (seven of 12 patients) at one month after the second treatment and in all patients at one month after the final treatment. All patients reported transient post-treatment erythema, which faded after a few days. Clinically evident relapse occurred in two of 12 patients (16.7%) one year after the final treatment session. Selective sebaceous gland electrothermolysis can be a safe and effective method of achieving consistent remission in acne.

Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72–104 au) than in corresponding concentrations of MAL (median 35–69 au) (P

Primary cicatricial alopecias (PCA) are a rare group of disorders, in which the hair follicle is the main target of destructive inflammation resulting in irreversible hair loss with scarring of affected lesions. The most typical clinical manifestation of PCA is the loss of visible follicular ostia. The histopathological hallmark of a fully developed lesion is the replacement of the hair follicle structure by fibrous tissue. PCA could share similar clinical manifestations and eventually lead to "burn-out" alopecia. Some subsets are hardly distinguishable histopathologically and the mechanisms that elicit such a destructive reaction have not been fully elucidated. Thus, the management of PCA represents one of the most challenging clinical problems for dermatologists. The aim of this review is to provide a concise and comprehensive summary of recent advances in PCA management, especially focusing on novel methodologies to aid diagnosis, and updates on our understanding of the etiopathogenesis. Dermoscopy, a new pathological preparation technique and direct immunofluorescence analysis enable more accurate clinicopathological diagnosis of PCA. Microarray analysis may be beneficial to distinguish PCA subtypes. Currently suggested mechanisms underlying PCA include loss of immune protection of stem cells, impaired stem cell self-maintenance, enhanced autoimmunity by pro-inflammatory cytokines and environmental/genetic predispositions. Interestingly, recent data indicates the association between lipid metabolism dysregulation and PCA development, implying an important role of the sebaceous gland dysfunction in the etiopathogenesis. Based on that hypothesis and observations, novel therapeutic approaches have been proposed, including the use of peroxisome proliferator-activated receptor-γ agonist for lichen planopilaris.

Chloracne is a characteristic marker of intoxication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or related compounds. Decreased lipogenesis is a prominent clinical sign in this disease. However, the activity of dioxins on human sebaceous glands is still unclear. In this study, the effects of TCDD on sebaceous gland differentiation were studied both in human skin samples maintained ex vivo and in cultured SZ95 sebocytes. Aryl hydrocarbon receptor (AhR) protein expression, the receptor for dioxin, was detected in SZ95 sebocytes. Its expression was markedly inhibited by TCDD. Furthermore, we detected a reduced release of neutral lipids (10(-10) -10(-8) M; P

Objective To investigate the distribution and density of conjunctival goblet cells (GC) and to study the anatomy and microscopic characteristics of glands associated with the eye in the guinea pig. Procedures Twenty-five guinea pigs were used. Meibomian gland openings were counted using biomicroscopy. Conjunctiva, eyelids and glands were embedded in glycol methacrylate and paraffin. Sections were stained with hematoxylin and eosin (H&E), periodic acid Schiff’s reaction (PAS) and Alcian blue (AB). Results Highest GC densities were found in the bulbar and palpebral region of the nasal conjunctiva (GC index: 13.7–16.4%). Lowest GC densities (GC index: 0.0–1.0%) were found in 3/4 limbal regions (nasal and temporal upper eyelid, temporal lower eyelid). Guinea pigs have 27.1 ± 3.0 (mean ± SD) meibomian gland openings in the upper lid and 25.7 ± 2.3 in the lower lid. Difference between upper and lower lid was significant (P = 0.037). Two subconjunctival sebaceous glands occur temporal to each eye. The Harderian gland is very large. In the lacrimal gland three different cell types were distinguished both according to the cell structure and histochemical staining. Conclusions Goblet cell densities are lower in guinea pigs than in dogs and horses. Positive staining with PAS and AB could be an indication that mucins are produced in the lacrimal gland. If so, they may contribute to the mucin layer of the tear film. Both the extraordinarily large Harderian gland and the subconjunctival sebaceous glands produce lipids and may contribute to the lipid layer of the tear film.

Lipid droplets (LD) are dynamic organelles that manage cellular lipid synthesis, storage and retrieval. Although LD-associated proteins, including the perilipin family (PLIN1-PLIN5), are essential for these functions, they have been poorly characterized in sebocytes. Here, we employed siRNAs to downregulate PLIN3 in SZ95 sebaceous gland cells and evaluated the consequences in lipid accumulation by nile red staining and mass spectrometry. Nile red staining revealed that siRNA-mediated downregulation of PLIN3 significantly impaired linoleic acid-induced lipid accumulation in SZ95 sebocytes. Mass spectrometry revealed that PLIN3 was implicated in the metabolism of linoleic acid, a lipid source used in the build-up of triglycerides, among other acyl lipids. Furthermore, the expression of key enzymes of sebaceous lipogenesis was altered in PLIN3-deficient sebocytes, consistent with the changes observed in the neutral lipid abundance, suggesting that PLIN3 functions are intertwined with the lipogenic pathways implicated in sebaceous lipogenesis, such as desaturation and triglyceride synthesis.

Skin biopsies from five Border terriers with histologically confirmed idiopathic, generalized sebaceous gland hyperplasia (Group A) were compared morphometrically to those from four unaffected Border terriers (Group B) and the unaffected dogs to biopsies from four other terrier breeds (Group C). Dogs in Group A had significantly higher numbers of sebaceous gland lobules per hair follicle than those in Group B (P = 0.020) but there was no significant difference between Groups B and C. The total sebaceous gland lobular area per hair follicle was significantly higher in dogs in Group A than Group B (P = 0.020) but there were no differences between Groups B and C. There were no significant differences in the size of the individual sebaceous gland lobules. There were no significant differences in the total number of basal or mature sebocytes between Groups A and B but significantly lower numbers of both cell types were seen in Group C compared to Group B. There were significantly more basal sebaceous cells undergoing mitosis in dogs in Group A than Group B (P = 0.017) but no significant difference between Groups B and C. These results indicate that the physical signs of sebaceous gland hyperplasia are caused by an increase in the number of sebaceous gland lobules and total lobular area. Border terriers may be genetically predisposed to the development of idiopathic generalized sebaceous gland hyperplasia compared with other dog breeds but also to sebaceous gland hyperplasia secondary to other dermatopathies.

Background The histogenesis of nevus sebaceous (NS) is unclear. Methods To elucidate the histogenesis of NS, cytokeratin (CK) profiles were examined immunohistochemically using 10 anti-keratin antibodies in the three stages of NS. Results In the first stage, stratified differentiated keratins (CK1 and 10) were reduced, and basal keratin (CK14) was increased in the epidermis and primitive follicular structure (PFS). In the second stage, in addition to reduced CK1 and CK10 expressions and increased CK14 expression, CK17 expression was strongly expressed in the sebaceous ducts in proportion to the development of sebaceous gland. In the third stage, CK14, CK17 and CK19 were expressed in secondary tumors. CK16 was not detected throughout all stages of NS. Conclusion These results suggest that NS is not hyperproliferative but involves hamartomatous differentiation with undifferentiated keratins.

Summary Isotretinoin (13-cis retinoic acid) is the most potent known inhibitor of sebum production. The multiple modes of action for isotretinoin, including suppression of sebaceous gland activity, normalization of the pattern of keratinization within the sebaceous gland follicle, inhibition of inflammation, reduction of growth of Propionibacterium acnes in a secondary manner and, as currently shown, normalization of the expression of matrix tissue metalloproteinases and their inhibitors make this compound the single most effective in the treatment of severe recalcitrant nodulocystic acne, and in the prevention of acne scarring. Several generic formulations for oral use have recently been introduced, in addition to the brand formulations Roaccutane and Accutane (Roche). This development, considering the high risk of teratogenicity associated with oral isotretinoin use, has led the European Commission and the European Medicines Agency (EMEA) to release a directive towards the harmonization of the Summary of Product Characteristics (SPC). This has similarities to US FDA regulations, a matter that caused the reaction of the Forum for the Improvement of Clinical Trials in Acne. Physician's experience, coupled with proper patient selection, dose adjustment or discontinuation of treatment, and routine monitoring for potential toxicity, has allowed the successful prevention and management of most adverse effects associated with isotretinoin.

Nonmelanoma skin cancers (NMSCs) consist of a variety of tumor types including basal cell carcinoma, squamous cell carcinoma, a variety of hair follicle tumors, and sebaceous gland tumors. Genetic alterations that alter the fate of multipotent stem cells are believed to influence NMSC phenotype. We previously generated a transgenic mouse line which constitutively expressed c-myc under the control of the K14 promoter (K14.MYC2). These mice exhibited an increase in size and number of sebaceous glands, suggesting that c-myc diverted multipotential stem cells to a sebaceous lineage. Our goal in the current study was to determine if alterations in the commitment of multipotent stem cells to different cell fates would influence tumor phenotype. To this end, we exposed K14.MYC2 mice to a chemical carcinogenesis protocol and discovered that these mice were predisposed to develop sebaceous adenomas. Our data demonstrate that genetic alterations that alter the fate of multipotent stem cells during embryonic development can markedly influence the phenotype of NMSC that develop following exposure to carcinogens.

Cytosolic and secretory carbonic anhydrase isoenzymes (CA-II and CA-VI, respectively) were detected by immunohistolocalization using specific canine CA-II and CA-VI antisera. CA-II and CA-VI were identified in glands associated with the canine lacrimal apparatus, such as lacrimal gland, superficial gland of the third eyelid (third eyelid gland) and tarsal gland. CA-II and CA-VI mRNA signals were also detected by reverse-transcriptase polymerase chain reaction in the same tissues. Some serous acinar cells and duct segments in the lacrimal gland and serous acinar cells in the third eyelid gland were immunopositive for anti-CA-II and CA-VI antisera. In particular, some immunopositive acini to CA-II and CA-VI on the edge of the third eyelid gland are histologically similar to sebaceous gland cells. Sebaceous gland cells in the tarsal and ciliary glands also showed immunopositivity to both CA antisera. CA-II and CA-VI gene transcripts were detected in the same regions. These results suggest that secreted CA-VI may form together with cytosolic CA-II, a high-activity isozyme mostly considered as a bicarbonate producer, in a mutually complementary system for the maintenance of bicarbonate levels to regulate pH in tear fluid and protect the corneal epithelia against injuries. In sebaceous gland cells in the lacrimal apparatus, CA-VI may be related to lipogenesis in an unknown function.

Acne is a very widespread cosmesis problem. Isotretinoin, a synthetic oral retinoid is used to treat acne, which is androgen dependent. Numerous side-effects occur from this treatment. 5-alpha-Reductase plays a critical role in normal and pathological androgen-dependent processes. We have taken the approach to develop a selective, effective, topically-applied 5-alpha-reductase inhibitor to modify unwanted or pathological processes in the pilosebaceous unit such as acne. Toward this goal, we have previously developed a selective liposome hair follicle targeting system. We demonstrate in this report that the 5-alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide (4-MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland. We have compared topical application of liposome 4-MA and solvent-formulated 4-MA and observed selective efficacy of topical application of liposome 4-MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4-MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (transferase deoxytidyl uridine end labeling) and by observation of condensed and fragmented nuclei. When 4-MA was topically applied formulated in ethanol and glycerol without liposomes, the selective efficacy was lost. Liposome 4-MA did not significantly affect prostate weight, testosterone/DHT ratios or bodyweight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA for pathological processes such as acne.

BACKGROUND Several studies have shown that hair follicle bugle cells can differentiate into hair follicles and contribute to the formation of the epidermis and sebaceous gland. Although many lines of evidence have suggested that the renewal and maintenance of the sebaceous gland depends on hair follicle bulge cells, direct evidence supporting the in vitro differentiation of follicle bulge cells into sebaceous gland cells has not been found. METHODS Rat vibrissa follicle bulge cells were isolated, cultured, and transfected with green fluorescent protein (GFPC1) plasmids carrying the peroxisome proliferator-activated receptor gamma2 (PPARgamma2 ) gene. The transfected cells were cultured in modified medium, and the morphologic changes of the cells were observed. Moreover, the expression of epithelial membrane antigens (EMAs) by the cells was detected by immunocytochemistry, and adipogenesis of the cells was evaluated. RESULTS After induction culture, the cell body enlarged gradually and contained abundant cytoplasm; lipid droplets appeared in the cytoplasm of some cells, and the cells resembled sebocytes of the sebaceous gland. The cells were positive on oil red O and EMA staining. The expression of PPARgamma2 mRNA and protein was significantly upregulated in PPARgamma2-transfected cells. The rate of oil red O-stained and EMA-positive cells was higher in PPARgamma2-transfected cells after induction than in bulge-PPARgamma2 cells and non-transfected bulge cells. CONCLUSIONS Rat vibrissa hair follicle bulge cells may differentiate into sebocytes in vitro, and the PPARgamma2 gene plays a crucial role.

Sebaceous gland oestrogen alpha (ERalpha) and progesterone (PR) receptor expression was examined immunohistochemically in 26 and 32 dogs respectively with sebaceous gland hyperplasia/adenomas, epitheliomas and carcinomas, and in the glands of 10 healthy controls. The mean percentage of ERalpha positive nuclei in control sebaceous glands was 21.31% compared with 11.5% in hyperplasia/adenoma-type lesions, although these values were not statistically different. In sebaceous gland epitheliomas and carcinomas, positive basal cells represented 7.86% and 3.53% of neoplastic cells respectively and these mean percentages were significantly lower in epitheliomas (P < 0.024) and carcinomas (P < 0.015) than in controls. The mean percentage of PR-positive nuclei in control sebaceous glands was 23.96%, similar to the 22.07% found in hyperplasia/adenoma-type lesions. In sebaceous gland epitheliomas and carcinomas, positive cells were scarce and represented 13.5% and 4.06% of neoplastic cells respectively. Differences in the percentage of positive cells between normal and pathological glands reached statistical significance for carcinomas (P < 0.043). In the control group there was greater PR (P < 0.001) and ERalpha expression (P < 0.014) in sebaceous glands in female dogs. The PR and ERalpha immunoreactivity in each category of neoplastic lesions could not be analysed because sample size was too small but when all the sebaceous gland tumours were grouped and analysed, no sex difference was found. The results suggest that oestrogen and progesterone receptor expression is reduced in some canine sebaceous gland tumours. These changes may represent a contributing factor for tumour growth or simply be a consequence of tumour progression.