elastin and Skin-Diseases

The perforating dermatoses are a group of disorders characterized by transepidermal elimination of a material from the upper dermis. The most widely accepted classification consists of four primary perforating disorders that are defined by the type of material eliminated and the type of epidermal disruption. Pathogenesis of the perforating dermatoses is poorly understood, but some appear to have a genetic component. There are also acquired forms, which have been associated with underlying systemic diseases and the use of certain drugs. In this report, we describe a perforating disorder that occurred secondary to leflunomide therapy. To our knowledge, this is the first case in which this has been reported. We also review the recent literature on medications associated with perforating disorders.

Topics: Adult; Drug Eruptions; Elastin; Epidermis; Female; Humans; Immunosuppressive Agents; Leflunomide; Skin Diseases; Vasculitis

Microneedles (MNs) are micron-sized, minimally invasive devices that breach the outermost layer of the skin, the stratum corneum (SC), creating transient, aqueous pores in the skin and facilitating the transport of therapeutic molecules into the epidermis. Following many years of extensive research in the area of MN-mediated trans- and intra-dermal drug delivery, MNs are now being exploited in the cosmeceutical industry as a means of disrupting skin cell architecture, inducing elastin and collagen expression and deposition. They are also being used as vehicles to deliver cosmeceutic molecules across the skin, in addition to their use in combinatorial treatments with topical agents or light sources. This review explores the chronology of microneedling methodologies, which has led to the emergence of MN devices, now extensively used in cosmeceutical applications. Recent developments in therapeutic molecule and peptide delivery to the skin via MN platforms are addressed and some commercially available MN devices are described. Important safety and regulatory considerations relating to MN usage are addressed, as are studies relating to public perception of MN, as these will undoubtedly influence the acceptance of MN products as they progress towards commercialisation.

Topics: Administration, Cutaneous; Collagen; Cosmetic Techniques; Drug Delivery Systems; Elastin; Epidermis; Equipment Design; Humans; Hyaluronic Acid; Intercellular Signaling Peptides and Proteins; Needles; Neovascularization, Physiologic; Patient Acceptance of Health Care; Peptides; Photochemotherapy; Porosity; Punctures; Rejuvenation; Skin Absorption; Skin Aging; Skin Diseases; Wound Healing

Short sequence amino acids or oligopeptides represent a relatively new and promising area of dermatology. Oligopeptides are defined as peptide sequences ranging from 2 to 20 amino acids. This class of proteins includes potent biologically active compounds, which can modulate various cellular and molecular processes. The medical potential of short sequence peptides was initially characterized many decades ago with the identification of biological mediators such as angiotensin, vasopressin, oxytocin and bradykinin. However, the role of oligopeptides in affecting biological activity within the skin has only recently been explored. Currently, the dermatologic use of protein peptide fragments is a rapidly growing field of research. Recent studies suggest that treatment with various biologically active peptides can result in favourable clinical outcomes such as for the treatment of hyperpigmentation disorders with tyrosinase inhibitors and the use of collagen synthesis modulators to diminish skin laxity. In this review, we explore the roles of biologically active short sequence peptides as potential therapeutics through the modulation of collagen, elastin and melanin synthesis.

Topics: Biological Products; Collagen; Elastin; Homeostasis; Humans; Melanins; Oligopeptides; Skin Diseases

The effects of chronic sun exposure on skin are readily apparent when skin not typically exposed to the sun and skin regularly exposed to the sun are compared. While the sun is not the only aetiological factor in the dynamic process of skin ageing, it is the primary exogenous cause among several internal and environmental elements. Thus, photo-ageing, the main focus of this article, is a subset of extrinsic skin ageing. The influence of the sun in extrinsic skin ageing, as well as its role in potentially altering the normal course of intrinsic (also known as natural or cellular) ageing, is discussed. Telomeres, the specialized structures found at the ends of chromosomes, are believed to be integral to cellular ageing as well as in the development of cancer. The ageing process, both intrinsic and extrinsic, is also believed to be influenced by the formation of free radicals, also known as reactive oxygen species. The loss of collagen is considered the characteristic histological finding in aged skin. Wrinkling and pigmentary changes are directly associated with photo-ageing and are considered its most salient cutaneous manifestations. Such photodamage represents the cutaneous signs of premature ageing. In addition, deleterious consequences of chronic sun exposure, specifically various forms of photo-induced skin cancer, are also linked to acute and chronic sun exposure. The only known strategies aimed at preventing photo-ageing include sun avoidance, using sunscreens to block or reduce skin exposure to UV radiation, using retinoids to inhibit collagenase synthesis and to promote collagen production, and using anti-oxidants, particularly in combination, to reduce and neutralize free radicals.

Topics: Antioxidants; Cell Division; Collagen; Dermis; Elastin; Environmental Exposure; Epidermis; Glycosaminoglycans; Humans; Hyaluronic Acid; Melanocytes; Reactive Oxygen Species; Skin Aging; Skin Diseases; Telomere

Topics: Animals; Elastin; Humans; Immunohistochemistry; Skin; Skin Aging; Skin Diseases; Sunlight

Elastin, the protein responsible for the elastic properties of vertebrate tissues, has been thought to be solely restricted to that role. As a consequence, elastin was conventionally described as an amorphous polymer. Recent results in the biomedical, biochemical and biophysical fields have lead to the conclusion that the presence of elastin in the extracellular space has very complex implications involving many other molecules. The present review describes the current state of knowledge concerning elastin as an elastic macromolecule. First, the genetic, biological, biochemical and biophysical processes leading to a functional polymer are described. Second, the elastic function of elastin is discussed. The controversy on elastin structure and elasticity is discussed and a novel dynamic mechanism of elasticity proposed. Finally, pathologies where the elastin molecule is involved are considered. This updated description of functional elastin provides the required background for the understanding of its pathologies and defines clearly the properties a substance should possess to be qualified as a good elastic biomaterial.

Topics: Animals; Aortic Valve Stenosis; Cutis Laxa; Elastic Tissue; Elastin; Humans; Skin Diseases; Structure-Activity Relationship; Williams Syndrome

Connective tissue microfibrils are key structural elements of the dermal matrix which play major roles in establishing and maintaining the structural and mechanical integrity of this complex tissue. Type VI collagen microfibrils form extensive microfibrillar networks which intercalate between the major collagen fibrils and are juxtaposed to cellular basement membranes, blood vessels and other interstitial structures. Fibrillin microfibrils define the continuous elastic network of skin, and are present in dermis as microfibril bundles devoid of measureable elastin extending from the dermal-epithelial junction and as components of the thick elastic fibres present in the deep reticular dermis. Electron microscopic analyses have revealed both classes of microfibrils to have complex ultrastructures. The ability to isolate intact native microfibrils from skin has enabled a combination of high resolution and biochemical techniques to be applied to elucidate their structure:function relationships. These approaches have generated new information about their molecular organisation and physiological interactions in health and disease.

Topics: Actin Cytoskeleton; Animals; Basement Membrane; Blood Vessels; Cattle; Collagen; Connective Tissue; Elastin; Humans; Microscopy, Electron; Microscopy, Electron, Scanning Transmission; Skin; Skin Diseases; Skin Physiological Phenomena; Structure-Activity Relationship

Elastic fibers form a network that contributes to the elasticity and resilience of tissues such as the skin. Histopathologic and ultrastructural abnormalities in the elastic fibers have been observed in several diseases of the skin and other tissues. Recent cloning of several genes involved in elastic fiber architecture has lead to the approach of the study of elastic fiber genodermatoses through molecular analysis. However, in genodermatoses, such as pseudoxanthoma elasticum, many of the genes encoding elastic fiber components have been excluded by genetic linkage analysis. In recent years, mutations in several of the genes encoding elastic fiber proteins have been demonstrated in other diseases. These include mutations in the fibrillin 1 gene in the Marfan syndrome, and genetic linkage of congenital contractural arachnodactyly to fibrillin 2, and, most recently, demonstration of abnormalities in the Menkes syndrome gene in X-linked cutis laxa. The first disorders to involve mutations in the elastin gene itself are, surprisingly, cardiovascular and neurobehavioral disorders, such as supravalvular aortic stenosis and Williams syndrome. These findings suggest that additional, as yet undiscovered, components of the elastic fiber network in the skin may hold the key to unraveling the molecular basis of the elastin-related genodermatoses.

Topics: DNA, Recombinant; Elastic Tissue; Elastin; Gene Expression Regulation; Genes; Genetic Diseases, Inborn; Genetic Linkage; Humans; Molecular Biology; Polymorphism, Genetic; Skin Diseases

Cutaneous aging represents a complex situation in which at least two independent factors--innate aging and solar exposure--contribute to the development of degenerative changes in the dermis. The biochemical and ultrastructural evidence reviewed in this article indicates that reduced collagen deposition, as a result of diminished collagen biosynthesis and reduced proliferative capacity of the fibroblasts, could explain the development of dermal atrophy and would relate to poor wound healing in the elderly. At the same time, perturbations in the supramolecular organization of the elastic fiber network lead to alterations in the mechanical properties of the skin, as manifested by loose and sagging skin with reduced resilience and elasticity.

Topics: Aging; Collagen; Connective Tissue; Elastin; Humans; Skin Diseases

The recent progress made in understanding the normal biology and biochemistry of the extracellular matrix of human skin has allowed us to identify several different levels at which errors could be introduced into the structure and metabolism of collagen or elastin, the two major fibrillar components of the dermis. Currently, several heritable cutaneous diseases are known to display distinct collagen or elastin abnormalities. This article reviews some of the heritable cutaneous diseases and highlights those entities in which definite information on molecular alterations in collagen or elastin is available.

Topics: Adult; Collagen; Collagen Diseases; Cutis Laxa; Ehlers-Danlos Syndrome; Elastin; Fibroma; Humans; Male; Osteopoikilosis; Osteosclerosis; Pedigree; Skin Diseases; Skin Neoplasms

Cutaneous aging represents a complex situation in which at least two independent factors--innate aging and solar exposure--contribute to the development of degenerative changes in the dermis. The biochemical and ultrastructural evidence reviewed in this article indicates that reduced collagen deposition, as a result of diminished collagen biosynthesis and reduced proliferative capacity of the fibroblasts, could explain the development of dermal atrophy and would relate to poor wound healing in the elderly. At the same time, perturbations in the supramolecular organization of the elastic fiber network lead to alterations in the mechanical properties of the skin, as manifested by loose and sagging skin with reduced resilience and elasticity.

Topics: Adult; Aged; Aging; Chemical Phenomena; Chemistry; Collagen; Connective Tissue; Elastic Tissue; Elastin; Humans; Microscopy, Electron; Middle Aged; Reference Values; Skin; Skin Diseases; Sunlight

Several inherited syndromes characterized by abnormal elastic fibers decreased in number and size could be collected under the heading of inherited elastolysis. This morphological concept does not prejudge the causal mechanisms of the elastolysis involving dermis and/or other organs. The elastic fibers anomalies result mainly from elastin crosslinking defects, developmental disturbances or excessive proteolysis.

Topics: alpha 1-Antitrypsin Deficiency; Ehlers-Danlos Syndrome; Elastin; Homocystinuria; Humans; Marfan Syndrome; Menkes Kinky Hair Syndrome; Skin; Skin Diseases

This article reviews the diseases that may show epidermal perforation as a histologic feature. Many of these represent examples of transepithelial elimination (TEE), a mechanism by which the skin rids itself of abnormal substances. After a review of disorders in which perforation is an occasional finding, four diseases that have been considered essential perforating disorders are discussed: elastosis perforans serpiginosa (EPS), reactive perforating collagenosis (RPC), perforating folliculitis (PF), and Kyrle 's disease (KD). A review of the literature, including recent reports of perforating diseases associated with chronic renal failure, suggests that there may be considerable clinical and histologic overlap among PF, KD, and the adult form of "perforating collagenosis." A working classification for the perforating disorders is suggested.

Topics: Collagen Diseases; Elastic Tissue; Elastin; Folliculitis; Granuloma; Humans; Keratosis; Kidney Failure, Chronic; Microscopy, Electron; Pseudoxanthoma Elasticum; Skin; Skin Diseases

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Elastic Tissue; Elastin; Histocytochemistry; Humans; Infant; Microscopy, Electron; Middle Aged; Skin; Skin Diseases

Topics: Animals; Arteriosclerosis; Blood Vessels; Elastic Tissue; Elastin; Guinea Pigs; Humans; Lipid Metabolism; Pulmonary Emphysema; Skin Diseases; Tropoelastin

Topics: Animals; Arteries; Arteriosclerosis; Calcium; Collagen Diseases; Cricetinae; Elastic Tissue; Elastin; Humans; Lipid Metabolism; Lung; Microscopy, Electron; Models, Chemical; Molecular Conformation; Pancreatic Elastase; Pseudoxanthoma Elasticum; Pulmonary Emphysema; Skin Diseases; Tropoelastin

It is apparent that significant progress has been made in our understanding of the biosynthesis, modifications, and maturation of collagen and elastin. We now recognize and partially understand special reactions involved in hydroxylations within the cell and complex cross-linking processes occurring outside the cell. Recent experiments (191) have shown that in human diploid fibroblast cultures of limited doubling potential (191) the hydroxylation of collagen prolyl residues appears to be "age" or passage-level dependent. With increasing passage level of these cultures, both the ascorbate requirements and the extent of collagen hydroxylation decrease. "Young" cell cultures have a strong requirement for complete hydroxylation and without ascorbate there is only about 50% of the normal level. "Middle-aged" cultures show higher hydroxylation without and full hydroxylation with ascorbate, whereas "old" (or cultures close to "senescence") are incapable of full hydroxylation with or without ascorbic acid. Although the overall system may show some deterioration with increasing passage levels, it appears that with increasing passage levels other components in the cell replace the ascorbate dependence of the hydroxylase system to a greater exten. In some ways, aging WI-38 cultures begin to resemble some transformed cells in their biochemical reactions, although they continue to remain diploid and eventually lose the ability to replicate. It is not yet known whether old animals can produce collagen, which may now be underhydroxylated, perhaps contributing to certain senescent changes. Careful examination of the hydroxylation index of collagen produced in organoid cultures of tissue biopsies as a function of donor age might be informative, particularly if one looks at the quality of collagen by employing collagenase and other proteolytic digests with collagen (191). One could comare the levels of frequent and characteristic peptide triplet sequences such as Gly-Pro-Hyp to Gly-Pro-Pro, Gly-Ala-Hyp to Gly-Ala-Pro, or Gly-Pro-Hyl to Gly-Pro-Lys and others for evaluation of hydroxylation throughout the entire molecule or at selected sequences.

Topics: Amino Acid Sequence; Animals; Antibody Specificity; Ascorbic Acid; Collagen; Connective Tissue; Copper; Ehlers-Danlos Syndrome; Elastin; Epitopes; Homocystinuria; Humans; Hydralazine; Lathyrism; Marfan Syndrome; Molecular Conformation; Platelet Aggregation; Procollagen-Proline Dioxygenase; Skin Diseases; Syndrome

Topics: Aging; Amino Acids; Aneurysm; Animals; Arteriosclerosis; Brain Diseases; Copper; Deficiency Diseases; Elastic Tissue; Elastin; Endocardial Fibroelastosis; Growth Disorders; Hair; Humans; Inflammation; Lathyrism; Marfan Syndrome; Metabolic Diseases; Respiratory Tract Diseases; Skin Diseases

The first-ever application of high-frequency ultrasound combined with multiphoton tomography (MPT) and dermoscopy in a clinical trial is reported. 47 patients with different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases, and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond laser multiphoton tomograph and (iii) dermoscopes. Dermoscopy provides two-dimensional color images of the skin surface with a magnification up to 70 x. Depending on the ultrasonic frequencies from 7.5 MHz to 100 MHz, the signal depth varies from about 1 mm to 80 mm. Vertical ultrasound wide-field images provide fast information on depth and volume of the lesion. The 100 MHz ultrasound allows imaging with resolutions down to 16 μm (axial) and 32 μm (lateral). Multiphoton tomography provides 0.36 x 0.36 x 0.001 mm³ horizontal optical sections of a particular region of interest with submicron resolution down to 200 μm tissue depth. The autofluorescence of mitochondrial coenzymes, keratin, melanin, and elastin as well as the network of collagen structures can be imaged. The combination of ultrasound and MPT opens novel synergistic possibilities in diagnostics of skin diseases with a special focus on the early detection of skin cancer as well as the evaluation of treatments.

Topics: Adult; Aged; Aged, 80 and over; Coenzymes; Collagen; Elastin; Female; Fluorescence; Humans; Keratins; Lasers; Male; Melanins; Microscopy, Fluorescence, Multiphoton; Middle Aged; Skin; Skin Diseases; Skin Neoplasms; Tomography, Optical; Ultrasonics

Excessive exposure to solar radiation is associated with several deleterious effects on human skin. These effects vary from the occasional simple sunburn to conditions resulting from chronic exposure such as skin aging and cancers. Secondary metabolites from the plant kingdom, including phenolic compounds, show relevant photoprotective activities. In this study, we evaluated the potential photoprotective activity of a phytocomplex derived from three varieties of red orange (Citrus sinensis (L.) Osbeck). We used an in vitro model of skin photoaging on two human cell lines, evaluating the protective effects of the phytocomplex in the pathways involved in the response to damage induced by UVA-B. The antioxidant capacity of the extract was determined at the same time as evaluating its influence on the cellular redox state (ROS levels and total thiol groups). In addition, the potential protective action against DNA damage induced by UVA-B and the effects on mRNA and protein expression of collagen, elastin, MMP1, and MMP9 were investigated, including some inflammatory markers (TNF-α, IL-6, and total and phospho NFkB) by ELISA. The obtained results highlight the capacity of the extract to protect cells both from oxidative stress—preserving RSH (p < 0.05) content and reducing ROS (p < 0.01) levels—and from UVA-B-induced DNA damage. Furthermore, the phytocomplex is able to counteract harmful effects through the significant downregulation of proinflammatory markers (p < 0.05) and MMPs (p < 0.05) and by promoting the remodeling of the extracellular matrix through collagen and elastin expression. This allows the conclusion that red orange extract, with its strong antioxidant and photoprotective properties, represents a safe and effective option to prevent photoaging caused by UVA-B exposure.

Topics: Antioxidants; Citrus sinensis; Collagen; Elastin; Plant Extracts; Reactive Oxygen Species; Skin Aging; Skin Diseases; Ultraviolet Rays

Calcinosis cutis is defined as abnormal deposition of calcium salts in the skin and subcutaneous tissues. Dystrophic calcification, the most common form of calcinosis cutis, is associated with autoimmune connective tissue diseases. This condition is associated with severe pain and can affect the patient's quality of life and lead to long-term disability. Treatment is often challenging, and there is a very limited evidence base for potential treatments of calcinosis cutis associated with systemic sclerosis and dermatomyositis. Inkless tattoo is very similar to microneedling, a minimally invasive procedure stimulating the wound-healing cascade contributing to elastin and collagen formation as well as neovascularization. This technique has not been reported as a potential therapeutic option for calcinosis cutis. Here, we present a patient with calcinosis cutis in the setting of dermatomyositis that responded dramatically to inkless tattoo application. Our results support the need for future studies of microneedling in patients with this disorder.

Topics: Calcinosis; Calcium; Collagen; Dermatomyositis; Elastin; Humans; Quality of Life; Salts; Skin Diseases; Tattooing

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals' intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas-ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal-epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.

Topics: Aged; Aging; Elastin; Face; Forearm; Humans; Microscopy, Fluorescence, Multiphoton; Skin; Skin Aging; Skin Diseases

Topics: Bystander Effect; Cyclooxygenase 2; Elastin; Fibroblasts; Humans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Skin; Skin Aging; Skin Diseases; Ultraviolet Rays

Oxidative stress is associated with photoaging of the skin as well as with skin cancer, and is therefore, critical to monitor. Ultraweak photon emission (UPE) is extremely weak light generated during the oxidative process in the living body and has been used as a non-invasive and label-free marker for the evaluation of oxidative stress. However, the mechanism of UPE generation is not clear. Therefore, we aimed to elucidate the molecular mechanism underlying UPE generation by analyzing the spectra of UPE generated from biomolecules in the skin during ultraviolet A (UVA) exposure. The spectra of UVA-induced UPE generated from linoleic acid, linolenic acid, elastin, phospholipids, and 5,6-dihydroxyindole-2-carboxylic acid were measured, and the spectrum of human skin tissue was also obtained. The spectral patterns varied for the different biomolecules and the peaks were distinct from those of the skin tissue. These results suggested that the UPE generated from skin tissue is a collection of light emitted by biomolecules. Moreover, we proposed that UPE is generated through a photosensitization reaction and energy transfer. The identified characteristic spectral patterns of UPE can be useful to elucidate UVA-induced oxidative stress in the skin, with implications for prevention and treatment of photoaging and skin diseases.

Topics: alpha-Linolenic Acid; Elastin; Energy Transfer; Female; Humans; Linoleic Acid; Middle Aged; Oxidative Stress; Phospholipids; Photons; Photosensitivity Disorders; Skin; Skin Aging; Skin Diseases; Ultraviolet Rays

Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear.. To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2.. We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs). Gene and protein expression of LOXL2 was investigated using real-time reverse-transcription PCR and immunohistochemistry. Mutation analysis was performed using the Sanger method.. We observed decreased LOXL2 mRNA expression in lesional skin of patients with MDE (0.48 ± 0.16) compared with healthy skin of the same patients (1.5 ± 0.51) and normal skin of HCs (1.9 ± 0.13). Compared with healthy patient skin (epidermis 2.38 ± 1.6, dermis 1.2 ± 1), LOXL2 protein expression in lesional patient skin (epidermis 1.1 ± 0.7, dermis 0.3 ± 0.45) was significantly decreased (P < 0.04 and P = 0.02, respectively). Mutation analysis of the entire LOXL2 gene could be performed for five patients, all of whom were found to have at least one mutation in the LOXL2 gene. Three of these had a mutation in the promoter region (c.967 G>C, c.1022 C>T, and c.1025 G>A, respectively), and one of them also had a mutation in the splice region of intron 11/exon 12 (IVS11-1 G>A). Of the remaining two patients, one had a mutation in exon 3 (T1391), and the other had a mutation in exon 11 (C663Y).. Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.

Topics: Amino Acid Oxidoreductases; Elastic Tissue; Elastin; Genetic Predisposition to Disease; Humans; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin; Skin Diseases

Equol is a major isoflavone metabolite, and equol-producing bacteria have been isolated and characterized; however, fermentation has been performed with soybean-based products as substrates. Pueraria lobata has been reported as a plant with higher content of isoflavones.. The genome of new equol-producing bacteria, Lactobacillus paracasei JS1, was analyzed. Also, the effect of P. lobata extract fermented with L. paracasei JS1 (FPE) on the skin and intestinal immune response was examined. With gene expression analysis, it was proven that seven skin-related proteins, hyaluronan synthase-1, -2, -3, collagen, elastin, epidermal growth factor, and epidermal growth factor receptor were differentially expressed upon FPE treatment. The messenger RNA expression increased with treatment with the FPE, and a skin moisturizing effect was confirmed by a hematoxylin-eosin staining experiment. In addition, such an experiment showed that proinflammatory cytokines, tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1β, -4, and -6, were reduced in large intestine when treated with FPE.. L. paracasei JS1 has the ability to produce equol having beneficial effects on the skin. Moreover, FPE also has an inhibitory effect on inflammation cytokines in the large intestine. Thus, the novel and edible equol-producing L. paracasei JS1 and FPE have thepotential to be developed as nutricosmetic resources. © 2019 Society of Chemical Industry.

Topics: Animals; Collagen; Elastin; Equol; Fermentation; Humans; Hyaluronan Synthases; Interleukin-1beta; Intestinal Diseases; Lacticaseibacillus paracasei; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Probiotics; Skin Diseases

This study aimed to investigate the protective effects of bovine elastin hydrolysates on UV-induced skin photoaging in mice and to identify the potent antiphotoaging peptides. Results showed that the ingestion of elastin peptides could obviously ameliorate epidermis hyperplasia and fibroblast apoptosis, and increase the content of hydroxyproline and water in photoaging skin in vivo ( p < 0.05). Furthermore, four peptides with elastase inhibitory activity were purified and identified, including GLPY, PY, GLGPGVG, and GPGGVGAL. Interestingly, GLPY and GPGGVGAL exhibited the highest inhibition activity with 58.77% and 42.91% at 10 mΜ, respectively. This might be attributed to the N-terminal Gly, C-terminal Leu, and Pro at the third position of the N-terminus, which showed stronger affinity and interaction with elastase. Moreover, GLPY and GPGGVGAL could also inhibit the apoptosis of fibroblasts effectively at 50 μΜ ( p < 0.01). It suggested that elastin peptides had great potential to prevent and regulate skin photoaging.

Topics: Amino Acid Sequence; Amino Acids; Animals; Antioxidants; Binding Sites; Cattle; Cell Line; Cell Survival; Elastin; Extracellular Matrix; Female; Fibroblasts; Humans; Mice; Molecular Docking Simulation; Peptides; Protein Binding; Protein Conformation; Reactive Oxygen Species; Skin; Skin Aging; Skin Diseases; Ultraviolet Rays

The high prevalence of skin diseases and their visible symptoms result in major physical, emotional, and economic burden for which few solutions exist. To address this unmet medical need, topical delivery of RNAi such as siRNA holds many advantages including direct access to the diseased site, potent knockdown of disease symptoms, and limited off-target effects. Unfortunately, delivering drugs into skin is extremely difficult. To address these concerns, we present RNAi robed with ionic liquid moieties. Specifically, we show that robed-siRNAs can be synthesized by a simple two-step process from bulk materials. Robing affords tuneability of properties necessary for dermal drug delivery including octanol-water partitioning, skin transport, and cell internalization. The efficacy and safety of robed-siRNA for treating skin disease was confirmed by its ability to limit breakdown of elastin, a major cause of premature aging, following UVB exposure to human reconstructed skin tissue. Together, the data strongly support that therapeutic RNAi robed with ionic liquid moieties are a simple, scalable prodrug platform for treating skin disease.

Topics: Administration, Cutaneous; Animals; Drug Delivery Systems; Elastin; Gene Knockdown Techniques; Humans; Ions; Prodrugs; RNA, Small Interfering; Skin Absorption; Skin Diseases; Swine; Ultraviolet Rays

Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin.. To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders.. Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions.. Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo.. MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.

Topics: Adult; Aged; Aged, 80 and over; Elastin; Humans; Imaging, Three-Dimensional; Microscopy, Fluorescence, Multiphoton; Middle Aged; Pseudoxanthoma Elasticum; Skin Diseases

Actinic cheilitis (AC) is characterized by epithelial and connective tissue alterations caused by ultraviolet sunlight overexposure known as photodamage. Fibroblasts have been linked to photodamage and tumor progression during skin carcinogenesis; however, their role in early lip carcinogenesis remains unknown. The aim of this study was to assess the density of fibroblasts in AC and normal lip (NL) samples and determine their association with markers of lip photodamage.. Fibroblasts, mast cells, p53, COX-2, and elastin were detected in NL (n = 20) and AC (n = 28) biopsies using immunohistochemistry/histochemistry. Mast cell and fibroblast density and epithelial p53 and COX-2 expression scores were then obtained. Elastosis was scored 1-4 according to elastin fiber density and tortuosity.. Fibroblasts, mast cells, p53, COX-2, and elastosis were increased in AC as compared to NL (P < 0.001). Multivariate analysis showed an association between fibroblast and mast cell density at the papillary and reticular areas of AC and NL (P < 0.05). Papillary fibroblast density was also associated with epithelial p53 and COX-2 expression (P < 0.05). Increased fibroblast density, both papillary and reticular, was found in the high elastosis group (scores 3-4) as compared to the low elastosis group (scores 1-2) (P < 0.01). Increased reticular mast cell density was detected only in the high elastosis group (P < 0.01).. Fibroblasts are increased in AC, and they are associated with mast cell density, epithelial p53 and COX-2 expression, and actinic elastosis. Therefore, fibroblasts may contribute to lip photodamage and could be considered useful markers of early lip carcinogenesis.

Topics: Adult; Biomarkers; Cell Count; Cheilitis; Coloring Agents; Cyclooxygenase 2; Elastin; Epithelium; Female; Fibroblasts; Humans; Immunohistochemistry; Lip; Male; Mast Cells; Middle Aged; Skin Aging; Skin Diseases; Tryptases; Tumor Suppressor Protein p53

Morphological changes in the dermal collagen and elastin fibre network are characteristic for skin ageing and for pathological skin conditions of the dermis.. To characterize pathological and physiological conditions by multiphoton laser scanning tomography (MLT) in vivo, it is necessary to investigate and identify morphological alterations related to ageing.. In vivo MLT was used to image two-photon excited autofluorescence (AF) and second harmonics generation (SHG) in human dermis of 18 volunteers of different ages. Criteria for the evaluation of age-dependent morphological changes in MLT images were fibre tension and morphology, network pattern, clot formation and image homogeneity. These criteria were weighted and a score was calculated.. The resulting MLT-based Dermis Morphology Score is correlated with age (R2 = -0.90) and with the previously published SHG to AF Ageing Index of Dermis (R2 = 0.66). The two groups of young (age 21-38) and old (age 66-84) volunteers showed a significant difference in MLT score values (P < 0.001).. We could demonstrate an in vivo relationship between morphological characteristics of human dermis assessed by MLT and age. The present score allows the semi-quantitative evaluation of specific morphological changes of the dermal fibre network in ageing skin by in vivo AF and SHG imaging. This method will be useful for diagnostics of pathological conditions and their differentiation from ageing effects.

Topics: Adult; Aged; Aged, 80 and over; Collagen; Dermis; Dermoscopy; Elastin; Female; Humans; Image Processing, Computer-Assisted; Lasers; Linear Models; Male; Microscopy, Fluorescence, Multiphoton; Reference Values; Skin Aging; Skin Diseases; Tomography

A 12-year-old girl with trisomy 21 (Downs syndrome) presented with an approximate 2-year history of an asymptomatic eruption on the right upper arm and left lateral neck that was clinically and histologically diagnostic of elastosis perforans serpiginosa (EPS). EPS is a perforating dermatosis affecting the face, ear, neck, extremities, or trunk. It occurs with greater frequency in persons with trisomy 21, as well as some other genetic syndromes and after D-penicillamine therapy. It has also been reported as a sporadic, presumably unrelated disorder in several acquired diseases.

Topics: Child; Connective Tissue Diseases; Down Syndrome; Elastic Tissue; Elastin; Female; Humans; Skin Diseases

Topics: Angiography; Biopsy; Carotid Artery, Internal, Dissection; Causality; Cerebral Infarction; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Male; Middle Aged; Recurrence; Skin Diseases; Vertebral Artery Dissection

Actinic elastosis is characterized by an accumulation of elastotic material in the upper dermis and is considered to be a manifestation of ultraviolet-induced skin aging. To compare the structural components of the elastotic material in actinic elastosis with those in normal skin, skin specimens were stained with antibodies raised against various elastin-related proteins. Elastotic materials exhibited a strong reaction to the antibodies for elastin, microfibril-associated glycoprotein-1 (MAGP-1), MAGP-4, matrix metalloproteinase 1 (MMP-1), MMP-2 and MMP-3, but a diminished reaction to anti-MMP-9 antibody. Fibroblast cell lines from the upper dermis of affected and unaffected skin were established, and the mRNA levels of MMPs were determined. MMP-1 and -2 mRNA levels were found to be elevated approximately twofold in the fibroblasts from actinic elastosis. Since MMP-1 and -2 are considered to be major enzymes involved in the degradation of matrix components, the accumulation of elastotic materials in actinic elastosis may be related to the degradation process.

Topics: Aged; Aged, 80 and over; Blotting, Northern; Elastic Tissue; Elastin; Female; Fibrillins; Fibroblasts; Humans; Immunohistochemistry; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinases; Microfilament Proteins; Middle Aged; RNA, Messenger; Skin; Skin Aging; Skin Diseases; Sunlight

Topics: Adult; Elastin; Female; Fibroblasts; Humans; Isodesmosine; Skin Diseases

A 3-year-old Japanese girl presented with disseminated white papules on the trunk. A biopsied specimen of the lesional skin revealed a focal accumulation of elastic fibers in the mid to deep dermis. No skeletal involvement was detected. This case was considered to be elastic nevus without systemic involvement. Since an elevated elastin expression in the fibroblasts of typical Buschke-Ollendorff syndrome (BOS) has been reported, elastin and elastin-related protein mRNA levels in the cultured patient fibroblasts were determined. There were no significant differences of steady-state levels of elastin, fibrillin 1 and microfibril-associated glycoprotein 1 mRNAs between patient and matched control fibroblasts. Elastic nevus without skeletal involvement may be etiologically different from typical BOS.

Topics: Blotting, Northern; Child, Preschool; Elastin; Extracellular Matrix Proteins; Female; Gene Expression; Hamartoma; Humans; RNA, Messenger; Skin Diseases

We report a case of a complex hamartomatous lesion of the skin which presented in a 75-year-old woman as a painful nodule of the palm. Histology showed eccrine glands, fat, angiomatous vessels, and neurovascular glomic-like bodies, variously admixed and immersed in a cellular, fibroblastic stroma. The name palmar cutaneous hamartoma is proposed for this unusual lesion.

Topics: Actins; Aged; Elastin; Female; Hamartoma; Hand; Histocytochemistry; Humans; Immunohistochemistry; S100 Proteins; Skin Diseases

Topics: Elastic Tissue; Elastin; Humans; Skin Diseases

Hairless (SKH-1) mice were mated with Beige (C57B/bb) mice to produce a hairless mouse deficient in neutrophil elastase (hhbb). These mice were exposed to 0.09J UVB irradiation for 5 months to see if neutrophil elastase was an important factor in elastin remodeling and development of solar elastoses. Analysis of peritoneal neutrophils confirmed that the hhbb mouse was deficient in elastase, retaining only 10% as much activity as the normal littermates (hhHb). Skin MPO activity was equally elevated in all the mice receiving UVB suggesting an equal influx of inflammatory cells. The absolute breaking strength of the skin in both the hhBb and hhbb mice was not altered by UVB treatment over the 5 month exposure period. Elastin quantitated biochemically as desmosine, or visualized histologically, was increased following UVB exposure in the normal mice. In the elastase deficient mice, however, the elastin fibers appeared to be unaffected by exposure to UVB irradiation at this level. The results suggest that neutrophil elastase is an important mediator in the development of solar elastosis resulting from continued exposure to UVB irradiation.

Topics: Animals; Chemotaxis, Leukocyte; Desmosine; Disease Models, Animal; Disease Progression; Elasticity; Elastin; Female; Male; Mice; Mice, Hairless; Neutrophils; Pancreatic Elastase; Skin; Skin Aging; Skin Diseases; Ultraviolet Rays; Up-Regulation

Only nine cases of Costello syndrome have been described so far. No definitive pathologic abnormalities have been found on skin biopsies. We undertook a quantitative study of the elastic tissue of the skin in one case of Costello syndrome in order to obtain objective scores of area, fragmentation, branching and texture of the elastic tissue, comparing it to cutis laxa syndrome, Ehlers-Danlos syndrome and normal skin. The results showed an increasing fragmentation score and loss of anastomosing points in elastic tissue in Costello syndrome and cutis laxa syndrome in relation to normal skin. Thus, we conclude that image analysis revealed, in Costello syndrome, a state of disorder akin to that of cutis laxa syndrome. Therefore, both syndromes might have a common pathogenesis as far as elastic tissue is concerned. However, other cases should be analyzed to validate our conclusions on statistical grounds.

Topics: Child; Elastin; Humans; Image Processing, Computer-Assisted; Male; Skin; Skin Diseases

Two cross-links unique to elastin, desmosine and isodesmosine were measured and compared in skin tissue (left upper arm) from 10 patients with amyotrophic lateral sclerosis (ALS) and from seven age-matched controls. The contents of desmosine and isodesmosine were significantly decreased (p < 0.01 and p < 0.01, respectively) in patients with ALS compared with those of controls, and were negatively and significantly associated with duration of illness in ALS patients (r = -0.77, p < 0.01 and r = -0.65, p < 0.05, respectively). The decline in skin desmosine and isodesmosine is more rapid in ALS than in normal ageing. Thus cross-linking of skin elastin is affected in ALS.

Topics: Aged; Amyotrophic Lateral Sclerosis; Elastic Tissue; Elastin; Female; Histocompatibility; Humans; Isodesmosine; Male; Middle Aged; Skin; Skin Diseases

Elastosis perforans serpiginosa (EPS) is an uncommon skin disease characterized by transepidermal elimination of abnormal elastic fibers. The disease is frequently associated with congenital connective tissue disorders or Down's syndrome. The pathogenesis of EPS is still unclear. There are a few reports in the literature about a familial occurrence of EPS in which different modes of inheritance are suggested. To support the hypothesis of a congenital origin of the disease, we have studied another family with EPS.. In this study, we describe a family in which two sisters and a brother were affected by EPS. The father and three paternal uncles were most probably affected by the same disease. There were no signs of other congenital connective tissue disease in the family members.. An autosomal dominant mode of inheritance with variable expression of EPS is suggested.

Topics: Adult; Aged; Atrophy; Cicatrix; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Humans; Keratins; Keratosis; Male; Middle Aged; Neck; Skin Diseases

Heterologous elastin particles were injected into the deep dermis or below the panniculus carnosus of hairless mice. A granulomatous tissue reaction with concomitant giant cell formation occurred around the implanted elastin in the early stages and, subsequently, calcium deposition with disappearance of the histiocytes and giant cells occurred in the later stages. Ultrastructural study revealed that some elastin particles were engulfed by the giant cells; others underwent calcification but remained intact. The heterologous collagen used as a control also induced a granulomatous tissue reaction, but did not undergo calcification and gradually disappeared. These results suggest that the heterologous elastin and collagen particles exhibit different susceptibilities to digestion. However, it is not clear why the heterologous elastin underwent calcification.

Topics: Animals; Calcification, Physiologic; Collagen; Elastin; Granuloma, Giant Cell; Male; Mice; Mice, Hairless; Microscopy, Electron; Skin Diseases

The lesions of nine patients with early striae distensae (SD) during puberty were examined by light and electron microscopy. Specific changes were seen in very early stage SD, and in clinically uninvolved skin 0.5 to 3 cm remote from the edge of the long axis of the SD lesions. Sequential changes of elastolysis accompanied by mast cell degranulation appeared first, followed by an influx of activated macrophages that enveloped fragmented elastic fibers. The relationships among elastic fibers, mast cells, and macrophages seen in the present work suggest their critical roles in the process of SD formation, especially in the early stage. Our results also indicate that the elastic fiber is the primary target of the pathological process, and the abnormalities extend as far as 3 cm beyond the lesion into normal skin.

Topics: Adolescent; Adult; Atrophy; Cell Degranulation; Collagen; Elastin; Female; Humans; Macrophages; Male; Mast Cells; Microscopy, Electron; Puberty; Skin; Skin Diseases

We studied an 86-year-old Japanese man with linear focal elastosis. The lesions were asymptomatic yellow striae in the lumbar region, histologically composed of massive, well-demarcated basophilic fibers that stained positively with elastic tissue stains. Electron microscopy revealed fine, reticular or granular electron-dense materials, and elastic fiber microfibril-like materials in the matrix, in addition to numerous mature and immature elastic fibers. These findings suggest that active elastogenesis was occurring in the lesions. The four cases reported so far have the three common features of age, sex, and lesion location.

Topics: Actin Cytoskeleton; Aged; Aged, 80 and over; Cytoplasmic Granules; Cytoskeleton; Elastic Tissue; Elastin; Fibroblasts; Humans; Male; Microscopy, Electron; Skin Diseases

Abnormalities in the amount of skin elastin occur in several cutaneous disorders. The number of elastic fibers is increased in elastotic disorders such as pseudoxanthoma elasticum (PXE) and cutis rhomboidalis nuchae (actinic elastosis, AE) and is decreased in elastolytic disorders such as cutis laxa (CL). We describe a procedure to quantify desmosines and elastin in small amounts of skin using high-performance liquid chromatography (HPLC). Biopsies were obtained from normal, nonsolar exposed skin and from the lesional skin of patients with PXE, cutis rhomboidalis nuchae, and CL. Specimens were subjected to hot alkali treatment and the desmosines were released by acid hydrolysis and quantified by HPLC. The mean value for normal skin was 252 +/- 28 ng desmosines per milligram wet weight (SD, n = 5). The disorders of elastosis (PXE and AE) demonstrated a two- to fivefold increased content of desmosines. In contrast, the elastolytic disorder (CL) had only 20% of the normal content of desmosines. Furthermore, PXE and normal skin elastins had the same amount of desmosines per milligram purified elastin. This method could be used to evaluate the extent of elastosis or elastolysis in a particular lesion.

Topics: Adult; Aged; Amino Acids; Chromatography, High Pressure Liquid; Cutis Laxa; Desmosine; Elastin; Humans; Isodesmosine; Middle Aged; Pseudoxanthoma Elasticum; Skin; Skin Diseases

The term penicillamine dermatopathy refers to the characteristic hemorrhagic skin lesions found in persons receiving long-term penicillamine therapy for either Wilson's disease or cystinuria. These lesions are thought to develop as a result of faulty collagen and elastin synthesis. We describe a patient with Wilson's disease who developed extensive penicillamine dermatopathy. In addition, histologic, immunochemical, and ultrastructural studies revealed multiple lymphangiectases with blood vessel to lymphatic anastomosis within these lesions, a finding not previously reported. The possible relationship to defective collagen and elastin formation are considered.

Topics: Adult; Biopsy; Collagen; Connective Tissue; Elastin; Hepatolenticular Degeneration; Humans; Immunoenzyme Techniques; Lymphangiectasis; Male; Microscopy, Electron; Penicillamine; Skin; Skin Diseases

Elastosis in benign and malignant breast lesions was studied by light microscopic immunohistochemistry for elastin and by electron microscopy. Upon immunohistochemical examination for elastin, elastosis, particularly in scirrhous-type ductal carcinoma, showed two characteristic staining patterns: fibrously and intensely stained elastic fibers and evenly stained elastic masses. Elastic fibers showing increased fibrous staining occurred mainly in the stromal areas, and were considered to be newly formed because they consisted of tannic acid-positive amorphous components and abundant microfibrils. Evenly stained elastic masses were observed mainly in the periductal areas and showed less intense stainability. These masses consisted of numerous fine amorphous components with plentiful microfibrils. In some regions within these masses, there were condensed accumulations of irregularly arranged small amorphous components associated with only a few microfibrils. These amorphous components had an ill-defined outline and were occasionally associated with spiralling collagen fibrils and cell debris. On the basis of these findings, the periductal evenly stained elastic masses were thought to be formed by excessive production of elastic fibers and degradation of pre-existing and newly formed elastic fibers.

Topics: Breast Neoplasms; Carcinoma; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Immunohistochemistry; Microscopy, Electron; Reference Values; Skin Diseases

Topics: Collagen; Connective Tissue; Connective Tissue Diseases; Elastin; Humans; Proteoglycans; Skin Diseases

In two cases of elastosis perforans serpiginosa (EPS) new clinical and laboratory data are described and discussed. In Case 1, EPS was triggered by penicillamine-D within an unusually short period (about one year). In Case 2, EPS was apparently primarily triggered by a vena puncture. In both cases the light and electron microscopic findings were strictly compatible with EPS. These findings are summarized. In the active lesions of both cases increased numbers of helper T-cells and Langerhans cells were shown, while cytotoxic-suppressor T-cells were nearly completely absent. Leu 3a+ cells and Leu 6+ cells were also present in the inactive central area of the lesions. The data presented may cast doubt on the relationship of immunological findings to pathogenetic events in the disease.

Topics: Adult; Connective Tissue Diseases; Elastin; Female; Humans; Male; Skin Diseases

Specimens of abdomen skin, comprising alternate areas of striae albae and healthy skin, were removed during surgical lipectomy from multiparous and obese women between the ages of 24 and 53 years. A flattening and thinning of the striae albae surface and the almost complete disappearance of dermal papillae was observed in paraffin and thin sections. The papillary dermis was found to be almost completely replaced by straight bundles of collagen fibres running parallel to the skin surface. Immunofluorescence data revealed in these bundles high positivity for type I collagen. The underlying reticular dermis was also found to contain large densely packed bundles of collagen fibres running parallel to the skin surface. Both papillary and reticular dermis collagen fibres were mainly arranged orthogonally to the main axis of the stria. Furthermore, the density of the collagen fibre bundles and the diameter of the collagen fibrils was found to be greater than that of the clinically healthy skin. A larger number of elastic fibres, which presented an abnormal ultrastructural appearance, were visible in pathological papillary and reticular dermis.

Topics: Adolescent; Adult; Collagen; Elastin; Epidermis; Female; Humans; Microscopy, Electron; Skin Diseases

Topics: Aged; Aged, 80 and over; Contractile Proteins; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Humans; Male; Middle Aged; RNA Splicing Factors; Skin; Skin Diseases; Sunlight

Sun-exposed and sun-protected skin obtained at post mortem from the nape of the neck in 14 subjects was immunostained using antisera to elastin, lysozyme, amyloid P component, and the plasma protease inhibitors alpha-I antitrypsin, alpha-I antichymotrypsin and alpha-2 macroglobulin. Both the normal elastic fibres in sun-protected skin, and elastosis in sun-exposed skin were positively immunostained for elastin, lysozyme and amyloid P component. Collagen fibres were unstained. No immunostaining of normal elastic fibres or elastosis in the skin was obtained with antisera to alpha-I antitrypsin, alpha-I antichymotrypsin or alpha-2 macroglobulin. It was concluded that the elastosis in sun-exposed skin does contain elastic fibres. The absence of immunostaining for plasma protease inhibitors probably indicates that the elastic material is mature, and not newly-formed.

Topics: Elastic Tissue; Elastin; Humans; Muramidase; Protease Inhibitors; Serum Amyloid P-Component; Skin; Skin Diseases; Sunlight

Topics: Elastin; Granuloma, Giant Cell; Humans; Necrobiosis Lipoidica; Phagocytosis; Skin Diseases

Reactive perforating collagenosis is an uncommon disorder and few accounts refer to ultrastructural features. This report includes a study by light and transmission electron microscopy of serially sectioned biopsies from early lesions in two patients. Immunohistological investigations utilizing antibodies to basement membrane, laminin, collagen and cytokeratin were also done. Collagen and elastin were demonstrated within the centre of the lesions and there was a defect in the basal lamina at the base of the lesion. The collagen, cytokeratin and the basal lamina in the lesions were antigenically similar to those in the surrounding normal skin. These results are compared with previous findings and discussed in the light of the current views on the pathogenesis of this disorder.

Topics: Basement Membrane; Child; Child, Preschool; Collagen; Collagen Diseases; Elastin; Epidermis; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Laminin; Male; Microscopy, Electron; Skin Diseases

Topics: Aging; Cutis Laxa; Elastic Tissue; Elastin; Humans; Pancreatic Elastase; Skin Diseases

This report reviews thirteen cases of generalized granuloma annulare. The light and electron microscopic appearance of intracellular elastin particles in eleven of these cases is described. These bodies were also noted in deep granuloma annulare, elastosis perforans serpiginosa, and a small percentage of localized granuloma annulare. They were not found in necrobiosis lipoidica.

Topics: Adult; Aged; Biopsy; Elastic Tissue; Elastin; Female; Granuloma; Granuloma, Giant Cell; Histiocytes; Histocytochemistry; Humans; Male; Middle Aged; Skin; Skin Diseases

Atrophoderma is a rare dermal disorder characterized by a patchy distribution of areas apparently devoid of elastic fibers. Skin fibroblast cultures were established from the normal and affected dermis of a patient with this disorder. Human tropoelastin was identified in culture medium by use of electroblotting and anti-elastin antisera. An enzyme-linked immunosorbent assay was used to establish that significantly less elastin accumulated in the media of cultured cells from lesional fibroblasts over a 3-d period. Since elastin biosynthesis in most tissues is under pretranslational control, molecular hybridization to a nick-translated genomic elastin probe was performed; however, elastin messenger RNA levels were equivalent in both cell strains. Both strains produced less elastin than did normal skin fibroblasts. Extracellular proteolysis of elastin was evaluated as a possible mechanism. Elastase activity was increased and porcine tropoelastin was degraded four times faster, on a per-cell basis, in lesional fibroblast cultures than in cells derived from an unaffected site. The two cell strains exhibited no significant differences in collagen production or collagenase activity. These results are the first demonstration of elastin production by cultured human skin fibroblasts, and they suggest that the primary defect in atrophoderma may be a result of enhanced degradation of newly synthesized elastin precursors.

Topics: Adolescent; Atrophy; Cells, Cultured; Collagen; Elastin; Female; Fibroblasts; Humans; RNA, Messenger; Skin; Skin Diseases; Tropoelastin

Previous morphologic observations have suggested abnormalities in the elastic fibers in a number of both inherited and acquired diseases. Recent progress made in understanding of the normal biology of elastin has allowed us to examine these diseases by biochemical means. In this review we are discussing the current status of the research on the elastin diseases with particular emphasis on clinical conditions affecting skin, as for example, cutis laxa, pseudoxanthoma elasticum, and the Buschke-Ollendorff syndrome. In addition, we present new data which appears to be the first demonstration of an elastin abnormality in the Marfan syndrome.

Topics: Connective Tissue Diseases; Cutis Laxa; Elastin; Humans; Marfan Syndrome; Menkes Kinky Hair Syndrome; Pseudoxanthoma Elasticum; Skin; Skin Diseases

Cytoid bodies represent roundish or polygonal, approximately cell-sized structures in histological sections. Such bodies have been reported to be of pathologic significance in several cutaneous disorders. Histological, immunological and electron microscopic investigations were performed in order to (1) characterize the different types of cytoid bodies in human skin, (2) elucidate their origin and nature and (3) determine their significance in cutaneous histopathology. A distinct identification of elastic globes, Russell bodies, Civatte bodies, amyloid bodies and cytoid fibrin bodies could be made. In addition, other substances such as nuclear or cytoplasmic debris, cytolytic fragments or basement membrane proliferations were found in form of cytoid aggregates in several dermatoses. However, none of the different groups of cytoid bodies was evaluated to be of pathognomonic significance for a specific disease. All of them are rather symptomatic for a number of anatomical or pathological principles and events in the dermo-epidermal junction area. Thus, the presence of cytoid bodies is not a major diagnostic aid in histopathology but may give valuable hints for a better interpretation of the morphogenesis of etiologically unrelated skin disorders.

Topics: Amyloid; Elastin; Fibrin; Humans; Lupus Erythematosus, Systemic; Skin; Skin Diseases; Skin Manifestations; Staining and Labeling

Ultrastructural and biochemical studies on the collagen and elastin fibres of the dermis from a patient with Elastosis perforans serpiginosa are described. Qualitative and quantitative alterations on collagen and elastin are shown, which give some evidence for considering the disease as a connective tissue defect.

Topics: Adolescent; Adult; Amino Acids; Collagen; Elastic Tissue; Elastin; Humans; Infant, Newborn; Male; Skin; Skin Diseases

Topics: Biopsy; Collagen; Elastin; Endoplasmic Reticulum; Fibroblasts; Humans; Microscopy, Electron; Mitochondria; Pigmentation Disorders; Progeria; Skin Diseases; Staining and Labeling

Topics: Adult; Amino Acids; Cellulose; Chromatography; Chromatography, Gas; Chromatography, Ion Exchange; Collagen; Dipeptides; Elastin; Humans; Male; Mass Spectrometry; Proline; Purpura; Skin Diseases

Topics: Age Factors; Aged; Animals; Capillaries; Collagen; Connective Tissue; Dermabrasion; Dogs; Elastic Tissue; Elastin; Female; Femoral Artery; Fibroblasts; Humans; Regeneration; Skin; Skin Diseases; Skin Physiological Phenomena

Topics: Carcinoma, Basal Cell; Connective Tissue; Elastic Tissue; Elastin; Glycosaminoglycans; Humans; Microscopy, Electron; Skin; Skin Diseases; Skin Neoplasms; Tuberculosis, Cutaneous

Topics: Cell Membrane Permeability; Collagen; Elastin; Epithelial Cells; Growth Inhibitors; Humans; Keratins; Langerhans Cells; Melanocytes; Mitosis; Skin; Skin Absorption; Skin Diseases; Skin Physiological Phenomena

Topics: Adult; Aged; Basement Membrane; Biopsy; Collagen; Cytoplasm; Elastin; Female; Humans; Langerhans Cells; Melanocytes; Microscopy, Electron; Middle Aged; Skin; Skin Diseases

Topics: Aged; Elastic Tissue; Elastin; Humans; Skin Diseases; Triamcinolone Acetonide

Topics: Amino Acids; Collagen; Detergents; Elasticity; Elastin; Forearm; Hand; Humans; Keratins; Lipids; Skin; Skin Diseases; Sulfhydryl Compounds

Topics: Aged; Cell Transformation, Neoplastic; Connective Tissue; Elastic Tissue; Elastin; Fibroblasts; Humans; Microscopy, Electron; Middle Aged; Photosensitivity Disorders; Protein Biosynthesis; Proteins; Radiation Effects; Skin Diseases; Skin Neoplasms; Ultraviolet Rays

Topics: Aging; Amino Acids; Carcinoma, Squamous Cell; Collagen; Elastin; Geriatrics; Histology; Humans; Keratosis; Keratosis, Actinic; Radiation Effects; Skin; Skin Aging; Skin Diseases; Skin Neoplasms; Sunlight; Ultraviolet Rays

Topics: Elastin; Humans; Proteins; Pseudoxanthoma Elasticum; Skin; Skin Diseases