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1.
J Drugs Dermatol ; 23(11): 992-997, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39496127

RESUMEN

Retinoids are derivatives of vitamin A prominently used in cosmeceuticals to reverse signs of photoaging. Retinaldehyde (retinal) is 10x more bioavailable than retinol and is gaining traction in the skincare industry for being the strongest over-the-counter retinoid. This study evaluated the efficacy and tolerability of a novel retinal formulation including peptides, ceramides, and lipids, designed to sustain the potency of the retinal and enhance delivery to reverse clinical signs of photoaging. This study was a trial of the test product (Retinal Night Advanced 0.1% Retinal Firming Treatment, Dr. Whitney Bowe Beauty, Greenwich, CT) in which 32 female subjects were enrolled. 47% of subjects had skin of color (Fitzpatrick Skin Type III-VI) and 57% had sensitive skin. Subjects applied the test product 3 nights weekly to the face, neck, and chest for 8 weeks. Fine lines of the face had 12% visible change by week 8 (P<0.0001). Fine lines on the chest showed progressive visible improvement of 11% at week 2 (P=0.0005) and 19% at week 8 (P<0.0001). There was a 19% improvement in visible hyperpigmentation of the face by the 8-week mark (P<0.0001). Visible texture of the face improved by 5% (P=0.0078) and pores improved by 20% at week 8 (P<0.0001). Patch testing revealed no signs of sensitization or irritation. This clinical study demonstrates that this retinal formulation is safe, well-tolerated, and effective in improving the appearance of fine lines, hyperpigmentation, texture, and pores. J Drugs Dermatol. 2024;23(11):992-997. doi:10.36849/JDD.8058R1 .


Asunto(s)
Retinaldehído , Envejecimiento de la Piel , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Femenino , Retinaldehído/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Péptidos/administración & dosificación , Péptidos/efectos adversos , Administración Cutánea , Anciano , Piel/efectos de los fármacos , Piel/patología , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Ceramidas/administración & dosificación , Cosmecéuticos/administración & dosificación , Cosmecéuticos/efectos adversos
2.
J Drugs Dermatol ; 23(10): 834-840, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39361692

RESUMEN

BACKGROUND: Inflammatory dermatologic conditions suitable for topical treatments benefit from a hydrating vehicle that improves the skin barrier without irritation. OBJECTIVE: This research was designed to assess skin barrier effects and aesthetic attributes of the vehicle for topical roflumilast cream (vehicle) vs a currently marketed ceramide-containing moisturizing cream (moisturizer). METHODS: This was a single-site, randomized, intraindividual, double-blind, controlled study conducted over 17 days. Patients (aged 18 years or older) with mild, symmetric asteatotic eczema of the lower extremities were enrolled to receive lower leg applications of the vehicle on one leg and moisturizer on the other. The primary efficacy endpoint was a change in transepidermal water loss (TEWL) from baseline to day 15. Secondary efficacy endpoints included change from baseline in TEWL at other study visits, change from baseline in hydration as assessed via corneometry, and patient- and investigator-rated assessments of the products. Safety and tolerability were also assessed. RESULTS: A total of 40 patients enrolled in the study. The primary efficacy endpoint was met for both treatments. A statistically significant difference in TEWL on day 1 favored the moisturizer, but no difference was seen between vehicle and moisturizer at any other timepoint. Both vehicle and moisturizer also met the secondary efficacy endpoint of change from baseline in hydration. LIMITATIONS: The sample size was small. CONCLUSIONS: The vehicle for roflumilast cream performed similarly to a leading, currently marketed, dermatologist-recommended, ceramide-containing moisturizer across all patient- and investigator-rated assessments of efficacy, tolerability, and aesthetic properties in patients with mild asteatotic eczema. J Drugs Dermatol. 2024;23(10):834-840. doi:10.36849/JDD.7958  .


Asunto(s)
Aminopiridinas , Benzamidas , Ceramidas , Ciclopropanos , Eccema , Crema para la Piel , Pérdida Insensible de Agua , Humanos , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Método Doble Ciego , Ceramidas/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Crema para la Piel/administración & dosificación , Eccema/tratamiento farmacológico , Eccema/diagnóstico , Adulto , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Benzamidas/uso terapéutico , Resultado del Tratamiento , Pérdida Insensible de Agua/efectos de los fármacos , Administración Cutánea , Anciano , Emolientes/administración & dosificación , Vehículos Farmacéuticos/administración & dosificación , Adulto Joven
3.
J Drugs Dermatol ; 23(9): 68821s3-68821s14, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39231086

RESUMEN

Lipids play an essential role in skin barrier health. With age, there is a natural reduction of physiological lipids such as fatty acids, ceramides, and cholesterol. The triple lipid restore cream is a moisturizer that contains an optimized lipid ratio for aging skin. The cream contains a 2:4:2 ratio of ceramides, cholesterol, and fatty acids that have been shown to best support aging skin. The triple lipid restore cream has been used in combination with energy-based procedures, to provide patients with comprehensive integrated skincare regimens. With limited clinical data and guidelines available in regenerative medicine, real-world cases serve as an invaluable guide for patients and dermatologists in navigating rejuvenation treatment plans. J Drugs Dermatol. 2024;23:9(Suppl 1):s3-14.


Asunto(s)
Rejuvenecimiento , Envejecimiento de la Piel , Crema para la Piel , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Crema para la Piel/administración & dosificación , Crema para la Piel/química , Femenino , Persona de Mediana Edad , Ceramidas/administración & dosificación , Colesterol/administración & dosificación , Resultado del Tratamiento , Técnicas Cosméticas , Terapia por Radiofrecuencia/métodos , Ácidos Grasos/administración & dosificación , Ácidos Grasos/química , Administración Cutánea , Terapia por Láser/métodos , Cicatrización de Heridas/efectos de los fármacos , Anciano , Masculino , Agujas , Inducción Percutánea del Colágeno
4.
Vet Dermatol ; 35(6): 617-625, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39118209

RESUMEN

BACKGROUND: Autosomal recessive ichthyosis leads to structural or biochemical changes that impair skin barrier function. HYPOTHESIS/OBJECTIVES: To assess (1) the phenotype and genotype in a litter of Jack Russell Terriers with autosomal recessive congenital ichthyosis (ARCI), and (2) the defective skin barrier and determine if a topical ceramide can modulate the barrier. ANIMALS: A healthy dam and litter of Jack Russell Terrier puppies (healthy male, affected male and female), one affected adult Jack Russell Terrier and one unrelated healthy Jack Russell Terrier. MATERIALS AND METHODS: A severe cornification defect was identified via examination of affected puppies. As the phenotype worsened, the affected puppies received a topical application of ω-0-acylceramide for 10 days. Before humane euthanasia, the skin barrier was evaluated via transepidermal water loss (TEWL), corneometry and pH in affected dogs. Genomic testing was performed, and skin samples were analysed by light and electron microscopy. RESULTS: Affected puppies were homozygous for the 1980 bp LINE-1 insertion in the TGM1 (transglutaminase 1) gene; the unaffected littermate and the dam were heterozygous carriers. ARCI puppies were underweight and had a severe hyperkeratotic phenotype that impaired mobility. TEWL was markedly higher in affected dogs. The cutaneous pH of affected puppies was higher than the normal littermate. Treatment of the skin with ω-0-acylceramide normalised the pH to match the littermate and decreased TEWL. Electron microscopy revealed marked attenuation of the cornified envelope. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with TGM1-deficient ARCI have an impaired skin barrier. Topical therapy can partially repair the barrier defect.


Asunto(s)
Ceramidas , Enfermedades de los Perros , Genotipo , Fenotipo , Transglutaminasas , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/genética , Transglutaminasas/genética , Femenino , Masculino , Ceramidas/administración & dosificación , Piel/patología , Piel/efectos de los fármacos , Administración Tópica , Ictiosis/veterinaria , Ictiosis/genética , Ictiosis/tratamiento farmacológico
5.
J Drugs Dermatol ; 23(6): 466-471, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38834224

RESUMEN

Xerosis is experienced by almost everyone at some time in their lives and the foundation of management of dry skin (both consumer- and healthcare professional--directed) rests on the use of moisturizers. Given the wide range of available moisturizers, counseling patients about selecting the optimum moisturizer for their individual situation relies on knowledge of ingredients and formulations. Traditionally, the main focus for many moisturizers centered on the core functional and structural role of ceramides within the epidermal barrier.  However, while a key aspect of transepidermal water loss and other skin barrier functions, components other than ceramides are equally essential in increasing moisturization. The skin's natural moisturizing factors (NMFs) are a complex mixture of water-attracting compounds such as amino acids, urea, lactate, pyrrolidone carboxylic acid (PCA), and electrolytes which play a fundamental role in preserving physiologic function by regulating the water content of the stratum corneum. By facilitating water retention, NMFs contribute significantly to the suppleness, elasticity, normal desquamation, and overall integrity of the skin barrier. Incorporation of NMFs into moisturizers addresses critical deficiencies in the skin's moisture balance that exist in xerotic and atopic skin, and in many skin disorders, mitigating signs and symptoms associated with xerosis and promoting optimal skin health. The biochemical composition of NMFs and the intricate interplay with epidermal homeostasis translate to a central role in moisturizers used for prophylactic and therapeutic management of various dry skin conditions, beyond ceramides alone. J Drugs Dermatol. 2024;23(6):466-471.     doi:10.36849/JDD.8358.


Asunto(s)
Ceramidas , Emolientes , Pérdida Insensible de Agua , Humanos , Ceramidas/administración & dosificación , Pérdida Insensible de Agua/efectos de los fármacos , Emolientes/administración & dosificación , Crema para la Piel/administración & dosificación , Administración Cutánea , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Epidermis/fisiología , Urea/administración & dosificación
7.
Skin Pharmacol Physiol ; 37(1-3): 32-39, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38768569

RESUMEN

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.


Asunto(s)
Ceramidas , Material Particulado , Hidrocarburos Policíclicos Aromáticos , Absorción Cutánea , Piel , Humanos , Absorción Cutánea/efectos de los fármacos , Hidrocarburos Policíclicos Aromáticos/farmacocinética , Hidrocarburos Policíclicos Aromáticos/administración & dosificación , Piel/metabolismo , Piel/efectos de los fármacos , Ceramidas/metabolismo , Ceramidas/administración & dosificación , Permeabilidad , Emisiones de Vehículos/toxicidad , Femenino , Adulto , Masculino , Contaminantes Atmosféricos , Administración Tópica , Administración Cutánea , Técnicas de Cultivo de Órganos , Persona de Mediana Edad
8.
J Cosmet Dermatol ; 23(8): 2743-2749, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38628085

RESUMEN

BACKGROUND: There is a dearth of effective treatments to counter retinol-induced skin irritation. OBJECTIVE: This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol. METHODS: An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double-blind, and vehicle-controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post-test. Subsequently, a 4-week consumer in-use test, randomized and double-blind in nature, was executed to substantiate the soothing effects of PLG. RESULTS: Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol-induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol-induced discomfort. The subsequent consumer in-use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone. CONCLUSION: To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol-induced irritation. Given their capacity to counter retinol-induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia-CR a* value can serve as a robust objective measure for interpreting patch test outcomes.


Asunto(s)
Eritema , Niacinamida , Pruebas del Parche , Vitamina A , Humanos , Adulto , Método Doble Ciego , Vitamina A/efectos adversos , Vitamina A/administración & dosificación , Femenino , Adulto Joven , Masculino , Eritema/inducido químicamente , Eritema/diagnóstico , Niacinamida/efectos adversos , Niacinamida/administración & dosificación , Ceramidas/efectos adversos , Ceramidas/administración & dosificación , Colesterol , Piel/efectos de los fármacos
9.
J Cosmet Dermatol ; 23(5): 1758-1765, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38299457

RESUMEN

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.


Asunto(s)
Acné Vulgar , Adapaleno , Administración Cutánea , Ceramidas , Fármacos Dermatológicos , Niacinamida , Índice de Severidad de la Enfermedad , Crema para la Piel , Humanos , Acné Vulgar/tratamiento farmacológico , Método Doble Ciego , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Femenino , Masculino , Crema para la Piel/administración & dosificación , Crema para la Piel/efectos adversos , Ceramidas/administración & dosificación , Adulto Joven , Adulto , Resultado del Tratamiento , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Adapaleno/administración & dosificación , Adolescente , Peróxido de Benzoílo/administración & dosificación , Peróxido de Benzoílo/efectos adversos , Quimioterapia Combinada , Emolientes/administración & dosificación , Combinación de Medicamentos
10.
J Dermatolog Treat ; 34(1): 2241587, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37592879

RESUMEN

BACKGROUND: The efficacy and safety of an over-the-counter (OTC) 1% colloidal oatmeal cream versus a ceramide-based prescription barrier cream in children with mild-to-moderate atopic dermatitis (AD) were previously described. OBJECTIVES: Here, findings are reported for the Black/African American subgroup. METHODS: Patients were randomized to 1% oatmeal cream or prescription barrier cream twice daily or as needed for three weeks. Assessments included Eczema Area and Severity Index (EASI) scores, Investigator's Global Atopic Dermatitis Assessment (IGADA) scores, and patients'/caregivers' assessment of eczema signs and symptoms. RESULTS: Overall, 49 Black/African American children aged 2-15 years with mild/moderate AD were included. At week 3, mean (SD) changes from baseline in EASI scores were -2.4 (1.7) with 1% oatmeal cream and -2.1 (2.3) with barrier cream; improvements were observed from week 1. At week 3, mean (SD) changes from baseline in IGADA scores were -0.6 (0.7) and -0.7 (0.6), respectively. Improvements in subjective ratings of signs/symptoms of eczema were observed. Both study treatments were well tolerated. CONCLUSION: OTC 1% oatmeal cream was at least as effective and safe as prescription barrier cream in this population, providing a novel, fast-acting, and cost-effective option for the symptomatic treatment of mild-to-moderate AD in Black/African American children.


Asunto(s)
Avena , Dermatitis Atópica , Niño , Humanos , Negro o Afroamericano , Población Negra , Ceramidas/administración & dosificación , Ceramidas/uso terapéutico , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/etnología , Eccema/diagnóstico , Eccema/tratamiento farmacológico , Eccema/etnología , Emolientes/administración & dosificación , Emolientes/uso terapéutico , Preescolar , Adolescente , Crema para la Piel/administración & dosificación , Crema para la Piel/uso terapéutico , Administración Cutánea
11.
Front Immunol ; 13: 967437, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36131915

RESUMEN

Brain lipid dysregulation is a hallmark of depression and Alzheimer's disease, also marked by chronic inflammation. Early-life stress (ELS) and dietary intake of polyunsaturated fatty acids (PUFAs) are risk factors for these pathologies and are known to impact inflammatory processes. However, if these early-life factors alter brain lipid homeostasis on the long-term and thereby contribute to this risk remains to be elucidated. We have recently shown that an early diet enriched in omega(ω)-3 PUFAs protected against the long-term negative effects of ELS on cognition and neuroinflammation. Here, we aim to understand if modulation of brain lipid and oxylipin profiles contributes to the detrimental effects of ELS and the protective ones of the diet. We therefore studied if and how ELS and early dietary PUFAs modulate the brain lipid and oxylipin profile, basally as well as in response to an inflammatory challenge, to unmask possible latent effects. Male mice were exposed to ELS via the limited bedding and nesting paradigm, received an early diet with high or low ω6/ω3 ratio (HRD and LRD) and were injected with saline or lipopolysaccharide (LPS) in adulthood. Twenty-four hours later plasma cytokines (Multiplex) and hypothalamic lipids and oxylipins (liquid chromatography tandem mass spectrometry) were measured. ELS exacerbated the LPS-induced increase in IL-6, CXCL1 and CCL2. Both ELS and diet affected the lipid/oxylipin profile long-term. For example, ELS increased diacylglycerol and LRD reduced triacylglycerol, free fatty acids and ceramides. Importantly, the ELS-induced alterations were strongly influenced by the early diet. For example, the ELS-induced decrease in eicosapentaenoic acid was reversed when fed LRD. Similarly, the majority of the LPS-induced alterations were distinct for control and ELS exposed mice and unique for mice fed with LRD or HRD. LPS decreased ceramides and lysophosphotidylcholine, increased hexosylceramides and prostaglandin E2, reduced triacylglycerol species and ω6-derived oxylipins only in mice fed LRD and ELS reduced the LPS-induced increase in phosphatidylcholine. These data give further insights into the alterations in brain lipids and oxylipins that might contribute to the detrimental effects of ELS, to the protective ones of LRD and the possible early-origin of brain lipid dyshomeostasis characterizing ELS-related psychopathologies.


Asunto(s)
Encéfalo , Ácidos Grasos Omega-3 , Estrés Psicológico , Animales , Masculino , Ratones , Ceramidas/administración & dosificación , Citocinas/metabolismo , Diglicéridos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Ácidos Grasos no Esterificados/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Insaturados/administración & dosificación , Interleucina-6/metabolismo , Lipopolisacáridos , Oxilipinas/metabolismo , Fosfatidilcolinas/administración & dosificación , Prostaglandinas/metabolismo , Triglicéridos/administración & dosificación
12.
Biochem J ; 478(19): 3621-3642, 2021 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-34648006

RESUMEN

Sphingolipid-mediated regulation in cancer development and treatment is largely ceramide-centered with the complex sphingolipid metabolic pathways unfolding as attractive targets for anticancer drug discovery. The dynamic interconversion of sphingolipids is tightly controlled at the level of enzymes and cellular compartments in response to endogenous or exogenous stimuli, such as anticancer drugs, including retinoids. Over the past two decades, evidence emerged that retinoids owe part of their potency in cancer therapy to modulation of sphingolipid metabolism and ceramide generation. Ceramide has been proposed as a 'tumor-suppressor lipid' that orchestrates cell growth, cell cycle arrest, cell death, senescence, autophagy, and metastasis. There is accumulating evidence that cancer development is promoted by the dysregulation of tumor-promoting sphingolipids whereas cancer treatments can kill tumor cells by inducing the accumulation of endogenous ceramide levels. Resistance to cancer therapy may develop due to a disrupted equilibrium between the opposing roles of tumor-suppressor and tumor-promoter sphingolipids. Despite the undulating effect and complexity of sphingolipid pathways, there are emerging opportunities for a plethora of enzyme-targeted therapeutic interventions that overcome resistance resulting from perturbed sphingolipid pathways. Here, we have revisited the interconnectivity of sphingolipid metabolism and the instrumental role of ceramide-biosynthetic and degradative enzymes, including bioactive sphingolipid products, how they closely relate to cancer treatment and pathogenesis, and the interplay with retinoid signaling in cancer. We focused on retinoid targeting, alone or in combination, of sphingolipid metabolism nodes in cancer to enhance ceramide-based therapeutics. Retinoid and ceramide-based cancer therapy using novel strategies such as combination treatments, synthetic retinoids, ceramide modulators, and delivery formulations hold promise in the battle against cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Antineoplásicos/metabolismo , Ceramidas/administración & dosificación , Ceramidas/metabolismo , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Tretinoina/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Quimioterapia Combinada/métodos , Humanos , Liposomas , Transducción de Señal/efectos de los fármacos , Tretinoina/metabolismo
13.
J Drugs Dermatol ; 20(4): s3-s9, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33852254

RESUMEN

Skin is a complex organ comprised of multiple cell types and microstructures that work in concert to serve critical functions and support the body’s homeostasis. It is the outermost, cornified layer of our body that is primarily responsible for the permeability barrier, protecting against external aggressors and preventing water loss from within. The understanding of the organization, functionality, and underlying mechanisms of the skin barrier has evolved greatly through the years. The formation of an intact and well-maintained stratum corneum (SC), where the permeability barrier resides, relies heavily on the differentiation of epidermal keratinocytes and the synthesis, release, localization, and binding of lipids that include principally ceramides, cholesterol, and free fatty acids. The in-depth research on SC barrier, its disruption in the pathogenesis of diseases, as well as on barrier responses to environmental insults, has enabled the development of modern therapeutics and topical care routines. Among them, ceramide-containing moisturizers have clinically demonstrated the ability to support the management of skin conditions such as atopic dermatitis and psoriasis by reducing the disease severity and recurrence and improving the patients’ perception of overall skin quality and health. This review focuses on the contributions of various barrier constituents to skin barrier function in health and pathological conditions, and how topical interventions containing essential barrier lipids support barrier restoration and provide relief. J Drugs Dermatol. 20(4 Suppl):s3-9. doi:10.36849/JDD.S589A.


Asunto(s)
Ceramidas/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Emolientes/administración & dosificación , Epidermis/patología , Psoriasis/tratamiento farmacológico , Administración Cutánea , Diferenciación Celular/efectos de los fármacos , Ceramidas/metabolismo , Colesterol/metabolismo , Dermatitis Atópica/patología , Epidermis/efectos de los fármacos , Ácidos Grasos no Esterificados/metabolismo , Humanos , Queratinocitos/fisiología , Metabolismo de los Lípidos/efectos de los fármacos , Permeabilidad , Psoriasis/patología , Pérdida Insensible de Agua/efectos de los fármacos
14.
J Drugs Dermatol ; 20(4): s10-s16, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33852255

RESUMEN

The skin barrier is a multifaceted microenvironment, comprised not only of structural and molecular components that maintain its integrity, but also a lipid matrix comprising an equimolar ratio of cholesterol, free fatty acids, and ceramides. Lipid abnormalities induced by environmental or pathological stimuli are often associated with impaired skin barrier function and integrity. Incorporation of skin lipids in skincare formulations to help fortify barrier function has become widespread. While there are resources available to study the barrier, a comprehensive evaluation of skin models, from in situ to in vivo, that focus on alterations of the lipid content, seems to be lacking. This article reviews current methods to evaluate the skin lipid barrier and touches upon the significance of using such models within the cosmetic field to study formulations that incorporate barrier lipids. J Drugs Dermatol. 20(4 Suppl):s10-16. doi:10.36849/JDD.S589B.


Asunto(s)
Cosméticos/administración & dosificación , Emolientes/administración & dosificación , Epidermis/efectos de los fármacos , Cuidados de la Piel/métodos , Animales , Técnicas de Cultivo de Célula , Línea Celular , Ceramidas/administración & dosificación , Ceramidas/metabolismo , Colesterol/administración & dosificación , Colesterol/metabolismo , Cosméticos/química , Modelos Animales de Enfermedad , Emolientes/química , Epidermis/fisiología , Epidermis/efectos de la radiación , Ácidos Grasos no Esterificados/administración & dosificación , Ácidos Grasos no Esterificados/metabolismo , Humanos , Técnicas de Cultivo de Tejidos , Rayos Ultravioleta/efectos adversos , Pérdida Insensible de Agua/efectos de los fármacos
15.
J Drugs Dermatol ; 20(4): s29-s35, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33852258

RESUMEN

The human skin, particularly the stratum corneum, serves as a protective barrier against exogenous factors, including ultraviolet radiation (UVR) and pathogen invasions. The impact of UVR on skin cancer and photoaging has been extensively studied. However, the direct impact of UVR on skin barrier integrity under clinical settings remains poorly explored. Due to their benefits in reducing inflammation and promoting skin barrier repair, ceramide-containing formulations can provide added photoprotection benefits. In this study, the efficacy of a ceramide-containing sunscreen and moisturizer were evaluated in preventing UV-induced skin surface barrier changes. Expert grading, instrumental, and tape-stripping assessments demonstrated that UVR induced erythema and hyperpigmentation and caused changes in skin cells surface morphological organization and maturation. Treatment with a ceramide-containing sunscreen and moisturizing cream routine reduced erythema and hyperpigmentation, improved skin hydration, and maintained normal superficial skin cells morphology and turnover after UVR. Our results indicate that barrier-enforcing lipids formulations can provide additional benefits in patient’s daily routine by strengthening the barrier and improving skin health overall against chronic sun exposure. J Drugs Dermatol. 20(4 Suppl):s29-35. doi:10.36849/JDD.S589E.


Asunto(s)
Ceramidas/administración & dosificación , Eritema/prevención & control , Hiperpigmentación/prevención & control , Rayos Ultravioleta/efectos adversos , Adolescente , Adulto , Emolientes/administración & dosificación , Emolientes/química , Eritema/diagnóstico , Eritema/etiología , Eritema/patología , Femenino , Voluntarios Sanos , Humanos , Hiperpigmentación/diagnóstico , Hiperpigmentación/etiología , Hiperpigmentación/patología , Masculino , Persona de Mediana Edad , Fotograbar , Piel/diagnóstico por imagen , Piel/efectos de los fármacos , Piel/efectos de la radiación , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Protectores Solares/administración & dosificación , Protectores Solares/química , Resultado del Tratamiento , Pérdida Insensible de Agua/efectos de los fármacos , Pérdida Insensible de Agua/efectos de la radiación , Adulto Joven
16.
J Oleo Sci ; 70(3): 417-430, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33658470

RESUMEN

Ceramide plays an important role in maintaining the skin barrier function. Aging and atopic dermatitis are known to reduce the levels of ceramide. Application of exogenous ceramide to the skin can restore the barrier function. In recent years, the effect of oral intake of ceramide has been demonstrated to improve the skin barrier function, and it has been marketed as a food supplement. Therefore, it is important to provide information on the safety of unintentional overdose of ceramide. This randomized, double-blind, placebo-controlled study was conducted in 30 healthy adults, aged between 20 and 60 years of age (both female and male). The subjects consumed either dietary supplement, comprising 1197 mg of acetic acid bacteria containing 9.06 mg of ceramide, or placebo for four consecutive weeks. Safety was evaluated based on physical measurements, blood test, urinalysis, adverse events, and side effects. The results showed several significant differences in physical measures and blood tests between the two groups. However, these differences were considered to be unrelated to the intake of the ceramide-containing acetic acid bacteria or placebo. Thus, no adverse effects or clinically concerning changes in physical, blood, and urine parameters were observed due to the excessive intake of the ceramide-containing acetic acid bacteria in the present study.TRIAL REGISTRATION: UMIN000035481.


Asunto(s)
Ácido Acético , Bacterias , Ceramidas/administración & dosificación , Suplementos Dietéticos , Administración Oral , Adulto , Ceramidas/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad , Fenómenos Fisiológicos de la Piel , Factores de Tiempo , Adulto Joven
17.
Mol Cancer Ther ; 19(12): 2621-2633, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33087509

RESUMEN

Therapies for head and neck squamous cell carcinoma (HNSCC) are, at best, moderately effective, underscoring the need for new therapeutic strategies. Ceramide treatment leads to cell death as a consequence of mitochondrial damage by generating oxidative stress and causing mitochondrial permeability. However, HNSCC cells are able to resist cell death through mitochondria repair via mitophagy. Through the use of the C6-ceramide nanoliposome (CNL) to deliver therapeutic levels of bioactive ceramide, we demonstrate that the effects of CNL are mitigated in drug-resistant HNSCC via an autophagic/mitophagic response. We also demonstrate that inhibitors of lysosomal function, including chloroquine (CQ), significantly augment CNL-induced death in HNSCC cell lines. Mechanistically, the combination of CQ and CNL results in dysfunctional lysosomal processing of damaged mitochondria. We further demonstrate that exogenous addition of methyl pyruvate rescues cells from CNL + CQ-dependent cell death by restoring mitochondrial functionality via the reduction of CNL- and CQ-induced generation of reactive oxygen species and mitochondria permeability. Taken together, inhibition of late-stage protective autophagy/mitophagy augments the efficacy of CNL through preventing mitochondrial repair. Moreover, the combination of inhibitors of lysosomal function with CNL may provide an efficacious treatment modality for HNSCC.


Asunto(s)
Ceramidas/administración & dosificación , Liposomas , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Mitofagia/efectos de los fármacos , Nanopartículas , Adenosina Trifosfato/metabolismo , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piruvatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello
18.
J Oleo Sci ; 69(11): 1497-1508, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-33055441

RESUMEN

The barrier function of the skin protects it from external stresses to which it is constantly exposed, such as dryness, ultraviolet rays, and chemicals. Lipids, in particular a type of sphingolipid known as ceramides, play a central role in the barrier function of the skin by preventing dryness. The number of ceramides in the skin is known to decrease with age, which has led to the development of a large number of anti-aging cosmetic products that contain ceramides. Recently, it has become evident that oral intake of ceramides can also improve the quality of the skin. To elucidate the effects of oral ceramide intake on skin moisture content, we conducted a randomized, double-blinded, placebo-controlled parallel comparative study in which males and females between 20 and 60 years of age who were worried about dry skin ingested a food with acetic acid bacteria containing 0.8 mg of dihydroceramide or a placebo for 12 weeks. Concurrently, we investigated the safety of continuous ingestion of the ceramide-containing food over 12 weeks. Oral intake of ceramide over the 12 weeks significantly improved stratum corneum hydration, i.e. the moisture content of the skin, and did not result in harmful effects in any of the participants.


Asunto(s)
Acetobacter , Agua Corporal/metabolismo , Ceramidas/administración & dosificación , Epidermis/metabolismo , Estado de Hidratación del Organismo/efectos de los fármacos , Piel/metabolismo , Administración Oral , Adulto , Ceramidas/farmacología , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Envejecimiento de la Piel/efectos de los fármacos , Adulto Joven
19.
J Oleo Sci ; 69(10): 1307-1315, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-32908096

RESUMEN

Ceramide, an intercellular lipid of the stratum corneum, plays an essential role in making the skin barrier. One problem with the use of medical adhesive tape or sheets for skin is that their repeated attachment and detachment may cause some damage to the skin. An attempt has been made to eliminate this problem by mixing ceramide into the adhesive of sheets, and has delivered excellent clinical results. This study aimed to investigate whether ceramide is transferred from the adhesive with added ceramide to the skin. An adhesive sheet was prepared by adding synthetic ceramide (CER) to UV-curable acrylic adhesive gel. After affixing the adhesive sheet to human skin for a certain period, it was peeled off and cut perpendicular to the adhesive surface. Synchrotron micro-infrared spectroscopy of the sectioned samples showed that the ceramide concentration in the gel sheet decreases as the application time to human skin increases. This is thought to be due to the release of CER from the gel sheet.


Asunto(s)
Adhesivos , Ceramidas/administración & dosificación , Ceramidas/metabolismo , Liberación de Fármacos , Absorción Cutánea , Piel/metabolismo , Cinta Quirúrgica , Ceramidas/análisis , Geles , Humanos , Espectrofotometría Infrarroja
20.
J Drugs Dermatol ; 19(8): 769-776, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32845590

RESUMEN

Background: Neonates and infants are susceptible to skin barrier disruption as their skin anatomically and functionally is still developing. The process of skin acidification plays a vital role in barrier maturation and the activation of enzymes involved in the extracellular processing of stratum corneum lipids. The current consensus paper explores challenges, and current treatment approaches in neonatal and infant normal and sensitive skin and the role of ceramides containing moisturizers. Methods: For this purpose, an expert panel of pediatric dermatologists and dermatologists discussed information from systematic literature searches, coupled with expert opinion and experience of the panel, to adopt eight statements. The consensus process consisted of a modified Delphi technique. Results: During the first years after birth, the neonatal and infant skin is more permeable to topical agents and, therefore, requires particular caution with topical skincare regimens. Mildly acidic or pH-neutral cleansers have benefits for neonates and infants. Skincare for neonates and infants should be safe, effective, and fragrance free as well as sensitizing agent-free. Additionally, the skincare should be pleasant to use, containing ingredients that benefit the lipid and water content of the SC, such as those products containing ceramides. Conclusion: Taking into consideration the maturation process of neonatal and infant skin, the application of moisturizers and cleansers containing barrier lipids may help maintain the protective skin barrier and soothe with long-term moisturizing benefits. J Drugs Dermatol. 2020;19(8) 769-776: doi:10.36849/JDD.2020.5252 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.


Asunto(s)
Ceramidas/administración & dosificación , Consenso , Epidermis/efectos de los fármacos , Guías de Práctica Clínica como Asunto , Cuidados de la Piel/normas , Técnica Delphi , Dermatología/métodos , Dermatología/normas , Emolientes/química , Epidermis/metabolismo , Humanos , Lactante , Recién Nacido , Metabolismo de los Lípidos/efectos de los fármacos , Absorción Cutánea/efectos de los fármacos , Cuidados de la Piel/métodos , Agua/metabolismo , Pérdida Insensible de Agua/efectos de los fármacos
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