cholecalciferol and Skin-Diseases

The human skin is constantly exposed to microbial pathogens but infections only rarely occur. Innate cutaneous immunity is a primary system for protection against infection, and antimicrobial peptides (AMPs) expressed in skin are essential defence molecules. The AMPs include molecules such as the defensins that were first characterized for their antimicrobial properties as well as other peptides and proteins first known for their activity as chemokines, enzymes, enzyme inhibitors and neuropeptides. Cathelicidins are unique AMPs that act as defensive and signalling molecules. Two different pathways are involved in this function: cathelicidins have direct antimicrobial activity and they also initiate a host of cellular responses in cytokine release, inflammation and angiogenesis. Several skin diseases are associated with cathelicidin dysfunction. In atopic eczema, for example, cathelicidin expression is suppressed, whereas in rosacea cathelicidin peptides are abnormally processed to forms that induce cutaneous inflammation and a vascular response. In psoriasis cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Current studies have unexpectedly identified vitamin D3 as a major factor for the regulation of cathelicidin expression. This finding may provide new strategies in the management of infectious and inflammatory diseases of the skin by targeting control of the expression and function of cathelicidin and other AMPs.

Topics: Cathelicidins; Cholecalciferol; Humans; Signal Transduction; Skin; Skin Diseases

Irradiation of human keratinocytes with UVB (280-320 nm) in vitro and in vivo activates the metabolism of 7-dehydrocholesterol to hormonally active calcitriol. The production of calcitriol in the skin strongly depends on the photosynthesis of vitamin D(3) which is biologically inactive in the first instance. Vitamin D(3) serves as the starting substrate for two subsequent enzymatic hydroxylation steps in epidermal keratinocytes. Both the amount of vitamin D(3) and the activity of anabolic and catabolic vitamin D hydroxylases determine the cutaneous level of calcitriol. The hormonally active metabolite of vitamin D(3) regulates a huge number of genes in keratinocytes, and thus acts in an autocrine and/or paracrine manner. This local pathway of vitamin D(3) is unique, but its relevance for healthy and diseased skin is widely unknown, yet. Experimental findings implicate several questions: (1) Is UVB-induced formation of calcitriol involved in regulation of growth and differentaition of epidermal cells as well as immunological and skin protective processes? (2) What endogenous and exogenous factors including drugs affect the cutaneous vitamin D(3) pathway? From a therapeutical point of view, it has been known for a long time that topical application of calcitriol and its analogs can improve hyperproliferative skin diseases like psoriasis. In spite of many encouraging studies in recent years, the fields of the routinely therapeutical application of calcitriol or vitamin D analogs in dermatology (e.g. treatment of immunological, inflammatory, malignancies and infectious skin diseases) have not been intensified. Why is that?

Topics: Calcitriol; Cholecalciferol; Humans; Signal Transduction; Skin; Skin Diseases; Skin Physiological Phenomena

Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases.

Topics: Animals; Bacteria; Cathelicidins; Cholecalciferol; Dermatitis, Atopic; Humans; Psoriasis; Rosacea; Skin; Skin Diseases

The paper is concerned with contemporary concepts on the role of androgens, estrogens, progesterone, mineralcorticosteroids, glucocorticoids and vitamin D3 and their signal transduction pathways in skin physiology, pathology and wound healing. The new therapeutic strategies based on mechanisms of steroid action have been presented. The classic, genomic pathway based on nuclear receptor activation is a well documented fact but less is known about indirect, nongenomic steroid effects. Steroids induced effects depend on their concentration, type of target cells and the receptors as well as accompanying side effects.

Topics: Androgens; Cholecalciferol; Dermis; Epidermis; Estrogens; Glucocorticoids; Humans; Mineralocorticoids; Progesterone; Signal Transduction; Skin; Skin Diseases; Steroids; Wound Healing

Epidermal keratinocytes are the site of both UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D(3) (25 OHD(3)) and the enzymatically controlled hydroxylation via 25-hydroxyvitamin D(3) to the biologically active final product 1alpha,25-dihydroxy vitamin D(3) (1alpha,25(OH)(2)D(3), calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and dermal immunocompetent cells. Calcitriol and other vitamin D-analogues are effective in the treatment of psoriasis because of their anti-proliferative and pro-differentiation effects. One mechanism for UVB-light therapy in psoriasis could be the induction of calcitriol synthesis. A better understanding of the metabolism of vitamin D(3) in the skin opens new perspectives for potential therapeutic applications of vitamin D analogues in inflammatory skin diseases. Further studies investigating the role of vitamin D(3) metabolism in the prevention of malignant skin disorders are needed.

Topics: Cholecalciferol; Dermatitis; Humans; Psoriasis; Skin Diseases; Ultraviolet Rays; Ultraviolet Therapy

Steroid-induced osteoporosis is the most common form of osteoporosis in the dermatological diseases, but there have been only few data concerning the treatment based on clinical evidences. For management of osteoporosis, the efficacy of vitamin D(3) and bisphosphonate had been demonstrated by meta-analytic approach. Ten dermatological patients in our clinic who had received long-term oral steroids and showed bone loss were treated with 5 mg/day of alendronate for one year, and showed significant increase in the bone mineral density of the lumbar spine. In dermatological patients requiring long-term systemic steroids, administration of drugs such as vitamin D(3) or bisphosphonate should be started earlier.

Topics: Aged; Alendronate; Anti-Inflammatory Agents; Bone Density; Cholecalciferol; Drug Therapy, Combination; Evidence-Based Medicine; Female; Humans; Lumbar Vertebrae; Male; Meta-Analysis as Topic; Middle Aged; Osteoporosis; Prednisolone; Skin Diseases

Many people consider a summer's day pleasant: warm and bright. The sun's ultraviolet rays do not contribute to the pleasure, and are biologically mainly harmful. As UV radiation does not penetrate any deeper than our skin, this organ has to be particularly well adapted to the UV exposure. The skin exploits the UV radiation for the synthesis of vitamin D3. Our day-to-day exposure suffices for this beneficial UV effect. Excessive exposure, as in sunbathing, only contributes to the adverse effects, like sunburn and suppression of cellular immunity in the short term, and 'photoaging' and skin cancer in the long term. The UVB radiation in sunlight is mainly responsible for these harmful effects, the UVA radiation to a far lesser extent (10-20% contribution). The UVA radiation from modern tanning equipment does not differ from that in sunlight, but UVA radiation does not lead to vitamin D3 production; it rather degrades vitamin D3 and a tan offers insufficient protection against the UVB radiation in full sunlight.

Topics: Cholecalciferol; Humans; Skin; Skin Diseases; Skin Neoplasms; Sunlight; Ultraviolet Rays

Most biologically active forms of vitamin D3 (1,25(OH)2D3) and its analogs have functions and therapeutic potential that extend beyond those of regulating bone mineralization and intestinal calcium transport.. We attempt to provide the rationale for the effectiveness of 1,25(OH)2D3 and its analogs in dermatology.. The recent literature on the mechanisms of action of 1,25(OH)2D3 were reviewed.. 1,25(OH)2D3 affects keratinocyte differentiation partly through its regulation of epidermal responsiveness to calcium. Calcium and 1,25(OH)2D3 interact in transcription of the genes required for differentiation and in the stability of the mRNAs produced from such genes.. An understanding of these mechanisms provides a rationale for treatment of various skin diseases with 1,25(OH)2D3 and its analogs and directs development of more effective therapy.

Topics: Calcification, Physiologic; Calcitriol; Calcium; Cell Differentiation; Cholecalciferol; Dermatologic Agents; Humans; Intestinal Mucosa; Keratinocytes; RNA, Messenger; Skin; Skin Diseases; Transcription, Genetic

Vitamin D3 analogs have been found to be effective in treating psoriasis.. We attempted to identify the targets and actions of vitamin D3 in the skin and to explore the availability of synthetic vitamin D3 analogs with selective actions on particular cell types or cell functions.. A review of the literature focused on the cellular targets of vitamin D3 in the skin and within the immune system. Furthermore, the use of novel vitamin D3 analogs in skin diseases other than psoriasis was reviewed.. The vitamin D receptor has been detected in most skin cells, which means that keratinization, hair growth, melanogenesis, fibrogenesis, angiogenesis, and immune-mediated processes are potential targets for vitamin D3. Vitamin D3 analogs have been synthesized with a higher therapeutic index or a higher degree of selectivity than the natural form of vitamin D3.. Vitamin D3 analogs with wide-ranging clinical applications may become available for dermatology.

Topics: Adjuvants, Immunologic; Biological Availability; Cholecalciferol; Connective Tissue; Dermatologic Agents; Forecasting; Hair; Humans; Immunity, Cellular; Keratins; Melanins; Neovascularization, Physiologic; Psoriasis; Receptors, Calcitriol; Skin; Skin Diseases

Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.

Topics: Binding, Competitive; Calcitriol; Calcium; Cholecalciferol; Heart; Humans; Immune System; Immunohistochemistry; Muscle, Smooth; Psoriasis; Receptors, Calcitriol; Skin; Skin Diseases; Tissue Distribution

Since the identification of the cholesterol derivative 1,25-dihydroxy-vitamin D3 and its analogues as potent immunomodulatory, proliferation- and differentiation-regulatory molecules, the amount of data available on the effects of these agents on the skin and its appendages has grown exponentially. This review outlines recent progress in the understanding of the molecular biology and pathophysiology of vitamin D, and new strategies for the treatment of skin diseases are discussed. Focusing on psoriasis and preliminary clinical experiences, we discuss possible therapeutic targets and perspectives for these multifunctional steroid hormones in dermatology.

Topics: Animals; Cholecalciferol; Humans; Psoriasis; Skin; Skin Diseases; Structure-Activity Relationship

One of the synthetic retinoids Etretinate has been used in dermatology for the various inflammatory keratosis, congenital hyperkeratotic disorders and etc., and plays an important role in the treatment of these otherwise intractable skin diseases. But, it still has various side effects, the most serious among which being teratogenicity, and contraception for at least two years after cessation of the drug is recommended because of its very long half life. Acitretin, a nonesterified analogue with a much shorter half life and Isotretinoin are also used in the USA and Europe. The latter is reported to be very effective to severe cystic acne. Apparently, better compounds with less toxicity and a shorter half life are needed. A topical application of retinoid is under clinical evaluation. A topical application of active vitamin D3 and its analogues are shown to be effective for psoriasis, one of the most common intractable skin diseases. Calcitriol is already used in several European countries, and 1,24-dihydroxyvitamin D3 successfully completed aclinical studies in Japan. Topical vitamin D preparations will be important and useful in dermatology in the near future. Although an action of active vitamin D on the skin is not fully understood, we speculate that it plays an important role in the regulation of epidermal growth and differentiation.

Topics: Aged; Cholecalciferol; Humans; Male; Skin Diseases; Vitamin A

Calcium has a major role in regulating epidermal functions, including cell proliferation, terminal differentiation, and cell-to-cell adhesion. Aberrations in calcium regulation have been noted in psoriasis when levels of the calcium binding protein calmodulin are elevated, and the normal calcium gradient within the epidermis is altered. Calcium may also be important in neoplasia because similar elevations in calmodulin have been noted in transformed cells. The function of calcium in mediating cell-cell adhesion may be important in understanding the acantholysis observed in pemphigus. The pemphigus foliaceus antigen appears to contain a calcium-sensitive epitope, and in pemphigus vulgaris, alteration in the function of calcium-sensitive cadherins may play a role in the production of acantholysis. Further understanding of the function of calcium in these processes may, in the future, allow us to alter calcium metabolism as a therapeutic intervention.

Topics: Animals; Calcium; Cell Adhesion; Cholecalciferol; Humans; Skin; Skin Diseases

Topics: Bone Diseases; Calcium; Carcinoma; Cholecalciferol; Chromatin; Dihydroxycholecalciferols; Ergocalciferols; Homeostasis; Humans; Hydroxycholecalciferols; Intestinal Diseases; Intestinal Mucosa; Kidney; Kidney Diseases; Liver; Liver Diseases; Parathyroid Diseases; Receptors, Drug; Skin Diseases; Thyroid Neoplasms; Vitamin D Deficiency

Vitamin D(3) has been called the "sunshine" vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many health benefits, however serum levels of vitamin D(3) have been decreasing over the last few decades and the lower levels of vitamin D(3) may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D(3)) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3).

Topics: Adolescent; Adult; Black or African American; Cholecalciferol; Dietary Supplements; Epidermis; Female; Humans; Middle Aged; Skin; Skin Diseases; Sunlight; Vitamin D Deficiency; White People; Young Adult

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5-10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13-1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30-100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Topics: Calcinosis; Calcium; Cholecalciferol; Denosumab; Dexamethasone; Humans; Hypercalcemia; Male; Middle Aged; Multiple Sclerosis; Off-Label Use; Skin Diseases; Treatment Outcome

Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Hypercalcemia; Rodent Diseases; Rodentia; Skin Diseases; Tooth

The usual methods of skin culture composed of organ culture, explant culture and cell culture were described. In organ culture of normal human skin, some blister diseases models have been used for the study of the mechanisms for producing the skin damage in pemphigus, bullous pemphigoid and epidermolysis bullosa hereditaria. Recent advances in epidermal cell culture system have furnished a potent tool for the study of keratinization at the molecular level. In the present status on tissue culture of human skin, these applications to clinical and laboratory investigations were discussed.

Topics: Animals; Carcinogens; Cell Differentiation; Cell Division; Cells, Cultured; Cholecalciferol; Culture Techniques; Cytological Techniques; DNA; Growth Substances; Humans; Keratinocytes; Second Messenger Systems; Skin; Skin Diseases

Topics: Adolescent; Adrenal Cortex Hormones; Age Factors; Child; Child, Preschool; Cholecalciferol; Humans; Infant; Skin Diseases; Syphilis, Congenital

Topics: Animals; Calcinosis; Calciphylaxis; Calcium; Cholecalciferol; Hair Removal; Keratins; Male; Microscopy, Electron; Phosphorus; Rats; Rickets; Skin Diseases

Topics: Cholecalciferol; Humans; Skin Diseases; Vitamin D; Vitamins

Topics: Cholecalciferol; Hormones; Humans; Skin Diseases; Vitamin D; Vitamins

Topics: Cholecalciferol; Skin Diseases