Decoding sebaceous gland functions and diseases: insights from domestic animals.

A hybrid mouse major urinary protein (MUP)/SV40 T antigen gene was microinjected into fertilized mouse embryos and the resulting transgenic mice analyzed for the regulated expression of the transgene. Available evidence indicates that the MUP gene used for the hybrid gene construct is expressed in both male and female liver and possibly mammary gland. Three different transgenic lines exhibited a consistent pattern of tissue specific expression of the transgene. As a consequence of transgene expression and T antigen synthesis in the liver, both male and female transgenic animals developed liver hyperplasia and tumors. Transgene expression and liver hyperplasia commenced at approximately 2-4 weeks of age, the same time that MUP gene expression is first detected in the liver. The expression of the transgene resulted in an immediate strong suppression of liver MUP mRNA levels but had relatively little effect on other liver specific mRNAs. From 4 to 8 weeks, the liver increased several fold in size, relative to non-transgenic littermates. Definitive tumor nodules were not apparent until 8-10 weeks. The transgene was also consistently found to be expressed in the skin sebaceous glands and the preputial gland, a modified sebaceous gland. The expression of the transgene in the skin sebaceous glands is consistent with the presence of MUP mRNA in the skin and a putative role for MUPs in the transport and excretion of small molecules. Occasional expression of the transgene in other tissues (kidney and mammary connective tissues) was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of “gene vestiges” in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.

Leukotriene B 4 as a mediator of early and late reactions to antigen in humans: The effect of systemic glucocorticoid treatment in vivo

Impaired Mitochondria Promote Aging-Associated Sebaceous Gland Dysfunction and Pathology

Sebaceous glands are adnexal structures, which critically contribute to skin homeostasis and the establishment of a functional epidermal barrier. Sebocytes, the main cell population found within the sebaceous glands, are highly specialized lipid-producing cells. Sebaceous gland-resembling tissue structures are also found in male rodents in the form of preputial glands. Similar to sebaceous glands, they are composed of lipid-specialized sebocytes. Due to a lack of adequate organ culture models for skin sebaceous glands and the fact that preputial glands are much larger and easier to handle, previous studies used preputial glands as a model for skin sebaceous glands. Here, we compared both types of sebocytes, using a single-cell RNA sequencing approach, to unravel potential similarities and differences between the two sebocyte populations. In spite of common gene expression patterns due to general lipid-producing properties, we found significant differences in the expression levels of genes encoding enzymes involved in the biogenesis of specialized lipid classes. Specifically, genes critically involved in the mevalonate pathway, including squalene synthase, as well as the sphingolipid salvage pathway, such as ceramide synthase, (acid) sphingomyelinase or acid and alkaline ceramidases, were significantly less expressed by preputial gland sebocytes. Together, our data revealed tissue-specific sebocyte populations, indicating major developmental, functional as well as biosynthetic differences between both glands. The use of preputial glands as a surrogate model to study skin sebaceous glands is therefore limited, and major differences between both glands need to be carefully considered before planning an experiment.

In order to analyze the hormonal effects of dehydroepiandrosterone (DHEA) in skin sebaceous glands, the precursor steroid was administered to ovariectomized (OVX) female Sprague-Dawley rats at a dose of 30 mg applied on the dorsal skin, twice daily, for 3, 6 and 12 months. In a parallel experiment, female OVX rats were treated with DHEA at the same daily percutaneous dose of 30 mg, alone or in combination with the antiandrogen Flutamide or the pure antiestrogen EM-800, for 12 months, in order to determine the androgenic and/or estrogenic components of DHEA action. Treatment of female OVX rats with DHEA resulted in a similar mild to moderate hyperplasia of the sebaceous glands of both dorsal (site of application) and ventral skin, as illustrated by an increase in the number and size of the acini. The above-indicated effects were observed at all time intervals studied, beginning at 3 months of treatment, and they were not further increased after longer term administration of DHEA (for 6 and 12 months). The addition of Flutamide to DHEA treatment completely prevented the DHEA-induced changes in the sebaceous glands, whereas the antiestrogen EM-800 had no effect. The present data indicate an exclusive androgenic stimulatory action of DHEA on the sebaceous glands, thus pointing out the importance of local intracrine DHEA transformation into androgens for skin anatomical integrity and function, while showing that estrogens, if active in rat skin, do not originate from DHEA.

Sebum is a complex lipid mixture that is synthesized in sebaceous glands and excreted on the skin surface. The purpose of this study was the comprehensive detection of the intact lipids that compose sebum. These lipids exist as a broad range of chemical structures and concentrations. Sebum was collected with SebuTape(TM) from the foreheads of healthy donors, and then separated by HPLC on a C8 stationary phase with sub 2 µm particle size. This HPLC method provided high resolution and excellent reproducibility of retention times (RT). Compound mining was performed with time of flight (TOF) and triple quadrupole (QqQ) mass spectrometers (MS), which allowed for the classification of lipids according to their elemental composition, degree of unsaturation, and MS/MS fragmentation. The combination of the two MS systems detected 95 and 29 families of triacylglycerols (TAG) and diacylglycerols (DAG), respectively. Assignment was carried out regardless of positional isomerism. Among the wax esters (WE), 28 species were found to contain the 16:1 fatty acyl moiety. This method was suitable for the simultaneous detection of squalene and its oxygenated derivative. A total of 9 cholesterol esters (CE) were identified and more than 48 free fatty acids (FFA) were detected in normal sebum. The relative abundance of each individual lipid within its own chemical class was determined for 12 healthy donors. In summary, this method provided the first characterization of the features and distribution of intact components of the sebum lipidome.

Major cat allergen Fel d I is produced consistently by skin and by sebaceous glands before being spread on the fur. Since cats have tubular anal glands secreting sebum, proteins and lipids, we looked at the possible presence of Fel d I in these secretions and compared the levels found to those already reported in other cat tissues or secretions. Thirty-seven cats were studied. Fel d I dosage in the anal sacs' secretions was performed using an enzyme linked immunosorbent assay (ELISA) method and total protein evaluation by the Bradford's method. The geometric mean Fel d I concentration was 41 U/g secretion which represents 3.4% of the total protein levels. This amount is the highest ever reported in cat tissues or secretions. The close association of Fel d I protein with skin sebaceous glands and anal sacs both with holocrine function and lipids' secretions in one hand, and the homology of chain I of Fel d I with some steroid-binding proteins in other hand, suggest a possible physiological role for Fel d I in the regulation of lipids on skin and cat fur.

For treatment of androgen-related skin deseases (ache, seborrhea) steroid antiandrogens - cyproterone acetate (CPA) [1, 2] and, to a lesser extent, spironolactone [!, 3] - are used in clinical practice in addition to antiinflammatory and an- timicrobial drugs. Antiandrogens which are similar to CPA suppress the growth and functional activity of the androgen- related skin sebaceous glands; however, the pronounced sys- temic effect of these compounds restricts their use in clinical practice. The possibility of local application of CPA, progesterone, and spironolactone was demonstrated experimentally. The advantage of local application of these compounds is the pos- sibility of decreasing their systemic effects; however, both CPA and spironolactone are more efficacious for systemic application [4]. To suppress iipogenesis in the skin sebaceous glands, inhibitors of 5ct-reductase can be used, for example, the methyl ester of 4-aza-4-methylandrost-3-oxo-1713-car- boxylic acid [5]. On the other hand, one of the most effective inhibitors, 4-aza-4-methyl-1713-diethylcarbamoylandrostan- 3-one (4-MA), does not exert a reliable effect on lipogenesis and the growth of the sebaceous glands of the hampster flank organ [6]. The search for compounds exhibiting decreased systemic (hormonal or antihormonal) effect and pronounced antiandro- genic effect on the skin sebaceous glands remains a topical problem. Modification of androgens (testosterone, dihydro- testosterone) used to separate their systemic and local effects may be a possible way for performing this approach. Destruc- tion of A ring (RU 38882) [7, 8] and introduction of addi- tional substituents into D and/or A rings (WIN 17765 [9, 10], SH-434 [1 I - 13]) are examples of such modifications. 17ct-Methyl- and 17or-ethyl derivatives of both testoster- one and dihydrotestosterone retain systemic androgenic ac- tivity. An increase in side chain length results in a decrease in systemic androgenic effects: 17ct-propyltestosterone (WIN 17765) exhibits local antiandrogenic properties without manifesting systemic activity [9]. Probably the lack of sys- temic antiandrogenic effects is explained by the rapid deacti-

Fel d I levels in cat anal glands

Background: Sebaceous adenoma is a benign tumour originating from the skin's sebaceous glands. These tumours can arise in older and middle-aged dogs, typically on various body parts, head, and extremities. The tumours can manifest as either lumps or ulcers. Ulcers may develop when the animal scratches the tumour mass. Purpose: Increase the insight and ability of veterinary practitioners in diagnosing and providing information regarding the treatment of sebaceous adenomas. Case: A nine-year-old Golden retriever dog was brought to the Bali Veterinary Clinic with a complaint of a lateral wound on the face skin of the right eye. Anamnesis revealed that the initial wound was a lump. Clinical examination showed a yellowish ulcer with a 2 cm diameter. Case Management: A hematology examination indicated mild anemia in the dog, while blood biochemistry revealed no abnormalities. Cytology confirmed that the ulcer was a sebaceous adenoma. The owner declined surgery for their pet, so treatment involved applying Bioplacenton® gel to the ulcer area to prevent further infection and accelerate wound healing. Conclusion: In this case, the ulcer wound can be concluded as a sebaceous adenoma. This tumour is benign and harmless, but it is advisable to remove the tumour mass if it impairs the animal's activity and prevents potential secondary infection.

The subclass Acari includes ticks (order Ixodida) and mites (Mesostigmata, Trombidiformes, Sarcoptiformes, several other orders). Ticks can transmit several pathogens and cause direct damage (e.g., blood depletion, skin lesions, and paralysis) to their host. Mites can cause lesions in the skin (e.g., mange-causing mites) of their hosts and affect their respiratory tract. Some free-living mites and their discarded cuticles can be aspired by and cause allergic reactions in humans. Systematic control of ticks on domestic animals and, eventually, in the environment is required. Control of mange-causing mites is usually done by treating affected patients and by avoiding sharing of clothes. Cleaning of houses, carpets, and bedclothes and reduction on humidity are efficient for the control of dust mites.

Demodex was first identified over 150 years ago, but only recently has it attracted wider interest as a contributor to chronic diseases such as acne rosacea or marginal blepharitis. Demodex is commonly found in the human population, in skin sebaceous glands or follicles. The frequency of Demodex infection increases with age, as it is mainly diagnosed after the age of seventy; however, it can sometimes be found in children and teenagers. Demodex is supposed to contribute to the development of marginal blepharitis or acne rosacea, but the pathogenic mechanisms have not yet been explained in detail. These diseases are chronic and the long-term treatment effects are not satisfactory. This paper presents the characteristics of Demodex as well as its prevalence in the pathogenesis of eye and skin diseases, and describes the diagnostics and treatment of these disorders.

Recently, linguistic communication and learning effect and even delivery of knowledge information and mutual communion was capacitated with English lip sync automation device and voice recognition technology based real time animation character in areas like movie, game, broadcasting, AR with application of animation lip sync. It connotes the possibility of these characters` lip sync using characteristic of animation to efficiently enhance the qualitative level of work in domestic animation creation`s linguistic expression with progress and application of automation technology. In a word, a study on development and practical use of Korean lip sync technique is needed to be made actively in industrial, technical progress of domestic animation. However, it is hard to find a research on commercialization method of Korean lip sync automation technique and excellent performance or example that these techniques were applied in domestic animation up to now. The reason that development using Korean lip sync technique on domestic animation passed unobserved could be found in problem of sociocultural awareness, production environment and functional value feature. First, in Korea, animation is recognized as subordinate part of movie genre, and sociocultural stereotype that persisted with dictionary definition and feature that unreal and non-objective illusion image with playful exaggeration and symbol that brings optical illusion through apparition of movement is also a problem. Second, labor-intensive method that mobilized many labor was used in production of traditional 2D animation, and since the production was done by specific worker with long acumen and experience, thus it requires long period of production and big consumption expense. Despite the fact that domestic animation is completed by overcoming poor surrounding with various risks, audiences yet feels that characters move their lip unlike the lines, and experience sound and image does not match, and it causes perception process of negative mental process and defensive mind like anger and distrust. These audiences of animation get interrupted to be empathized into true world that is essentially pursuing, and at the same time any kind of symbolic meaning and metonymic value also cannot be earned from animation. This researcher look at technical standard which will influence qualitative level of domestic creative animation in the future, and try to think visualization and synchronization problem in linguistic expression of character lip sync scene which is required in 3D animation in production side and audience side. This thesis try to study on need to develop related technology in the future and development plan by checking importance of Korean lip sync and current use state of technology in maker and audience of domestic animation. Also, looked at method and attitude for future creative animation to use technology with progress of animation Korean lip sync technology in technical side by emerging from non-linguistic act and behavior oriented research of animation. Also, in excellent cases of animation Korean lip sync, it could surpass the limit of children oriented domestic animation which massively produced with small scale and low budget, and contribute on newly illuminate and develop value and meaning of animation to more various and wider socio-cultural class.

Endometriosis coexisting with a dermoid cyst of the ovary is extraordinarily rare, although both these benign conditions are said to be common in women in the reproductive age group. There are only two previous case reports,which is evident from our literature review from January 1960 through January 2010. Acute abdomen is one of the greatest diagnostic challenges and easily ignored by the clinicians to exclude the possibility of gynecologic illness. A 35-year-old woman was referred by the doctor in Family clinic. She experienced a three-day period of severe right lower abdominal pain and intermittent vomiting. Ultrasonography identified a bilocular, cystic, hypoechoic, and hyperechoic tumor, 7 cm × 6 cm × 6 cm in the right adnexal region. Laparoscopic cystectomy was performed under the impression of ovarian cyst with torsion or hemorrhage. The frozen section was benign and appendiceal status was adequate. Histopathologic examination described an ovarian cyst composed of endometrial-type lining with stromacells (endometriosis) and benign teratoma tissue with plenty of skin appendages and sebaceous glands. We report this unusual and interesting ovarian mass to remind physicians that the usage of the Endobag after cystectomy, the benefits on minimizing operative time, spilled opportunity, and postoperative complications. Laparoscopic techniques for large ovarian masses might be considered. The experience of the surgeon is also very important to prevent misdiagnosis or complication. Further follow up is mandatory for this simultaneous finding of ovarian endometriosis with coincidental dermoid cyst as a separate pathology in single ovary of such a nature. It also presents a challenge to the clinicians and to the pathologists.