 Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
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- The Effects of Mucopolysaccharide Polysulfate on Steroid-Induced Tight
Junction Barrier Dysfunction in Human Epidermal Keratinocytes and a 3D
Skin Model-
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Abstract: Introduction: The long-term use of topical corticosteroids (TCS) is associated with side effects such as skin atrophy and barrier deterioration. Moisturizers, such as mucopolysaccharide polysulfate (MPS), have been reported to prevent relapses in atopic dermatitis (AD) when used in combination with TCS. However, the mechanisms underlying the positive effects of MPS in combination with TCS in AD are poorly understood. In the present study, we investigated the effects of MPS in combination with clobetasol 17-propionate (CP) on tight junction (TJ) barrier function in human epidermal keratinocytes (HEKa) and 3D skin models.Methods: The expression of claudin-1, which is crucial for TJ barrier function in keratinocytes, and transepithelial electrical resistance (TEER) was measured in CP-treated human keratinocytes incubated with and without MPS. A TJ permeability assay, using Sulfo-NHS-Biotin as a tracer, was also conducted in a 3D skin model.Results: CP reduced claudin-1 expression and TEER in human keratinocytes, whereas MPS inhibited these CP-induced effects. Moreover, MPS inhibited the increase in CP-induced TJ permeability in a 3D skin model. Conclusion: The present study demonstrated that MPS improved TJ barrier impairment induced by CP. The improvement of TJ barrier function may partially be responsible for the delayed relapse of AD induced by the combination of MPS and TCS.
PubDate: Sat, 25 Mar 2023 05:55:04 +010
- Skin physiology, mucosal functions and symptoms are modulated by grass
pollen and ozone double exposure in allergic patients-
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Abstract: Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under double exposure with pollen ozone in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA²LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss (TEWL) as a parameter for epidermal barrier function. The subjects’ general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function, increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE-duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms and are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose(time)-response relationship. The surface pH can be regarded as a possible modulatory mechanism.
PubDate: Thu, 16 Mar 2023 09:42:28 +010
- The epidermal environment’s influence on the dermal environment in
response to external stress-
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Abstract: Introduction: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. Methods: We employed ultraviolet irradiation B (UVB) (which does not reach the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed 1) inflammatory markers in keratinocytes; 2) matrix metalloproteases (MMP) levels and collagen degradation in fibroblasts; 3) Ex vivo organ-cultured human skin were treated with UVB. MMP levels and collagen degradation were examined; 4) Test whether the mixture of agent (agent cocktail) consists of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB is skin; and 5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on skin function. Results: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3 and -9 production was increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes Type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis, and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity and reduce the appearance of wrinkles. Conclusion: Epidermal Changes in epidermal environment and conditions in response to external stress, affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.
PubDate: Thu, 16 Mar 2023 06:46:13 +010
- Alterations in Epidermal Biophysical Properties in Autistic Children
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Abstract: Autism is a neurodevelopmental disorder. Individuals with autism can exhibit multiple neurological symptoms such as deficit in social communication, restricted interests and repetitive behaviors. Recent study showed that murine model of autism displays an increased transepidermal water loss (TEWL) and dry skin. But whether epidermal functions are also altered in children with autism is unknown. In the present study, TEWL, stratum corneum hydration and skin surface pH were compared between children with autism (N=56) and normal controls (N=48). Our results showed that children with autism exhibited lower stratum corneum hydration levels, higher TEWL and elevated skin surface pH in comparison to normal controls (p
PubDate: Tue, 14 Mar 2023 11:20:16 +010
- Development of an In Vitro Functional Assay to Evaluate the Occlusive
Properties of Moisturizers on Dry Skin-
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Abstract: Introduction: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to a lack of reliable efficacy measures using in vitro models. Methods: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. Results: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products.Conclusion: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions.
PubDate: Thu, 02 Mar 2023 12:08:03 +010
- Evaluation of a novel skin emollient cream on skin lipidome and lipids
organization-
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Abstract: Introduction: The stratum corneum (SC) matrix is composed of free fatty acids, cholesterol and ceramides (CERs), which play a key role in the skin barrier function. Changes in the composition and content of skin lipids will affect the function of the skin barrier. The effect of a glycerol/petrolatum-based emollient (G/P-emollient) cream on the lipid profiles of isolated ex vivo human SC and the SC of a reconstructed human epithelial (RHE) model were measured. Methods: The spatial organization of the cream and the isolated SC intercellular matrix was studied using X-ray diffraction. The inter-bilayer distance in the multi-lamellar lipid structures and lattice type were analyzed using small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), respectively. Lipidomic analysis using Shotgun Lipidomics was performed on reconstructed human epidermis (RHE) to quantify CER classes and chain lengths. This technology enables the analysis of thousands of lipids in a single biological sample. Results: The crystallized components of the cream are lipids, which were mainly packed in orthorhombic lattices, as well as hexagonal lattices and were similar to the SC structure. The cream penetrated the SC but did not alter the WAXS profile. It increased the amount of higher carbon number ceramides (> 42 carbons) and decreased lower carbon number ceramides (
PubDate: Wed, 08 Feb 2023 03:32:00 +010
- Skin care in neonates and infants - a scoping review
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Abstract: BackgroundSkin care is a basic, daily activity performed by formal and informal caregivers from birth until end of life. Skin care activities are influenced by different factors as e.g., culture, knowledge, industrial developments and marketing activities. Therefore, various preferences, traditions and behaviours exist worldwide including skin care of neonates and infants. Objective of this scoping review was to obtain an overview about the evidence of skin care activities in neonates and infants. Studies from 2010 were eligible if the population were (skin) healthy neonates and infants, if the concept were skin care interventions and if the context was at home, in a community setting, in a paediatric outpatient service or in a hospital. We searched for literature via OVID in Medline and Embase, in the Cochrane Library, in trial registries and for grey literature. SummaryWe identified 42 studies since 2010, which examined four main skin care interventions: bathing, wiping, washing, and topical application of leave-on products. Details of interventions were often not reported and if they were, they were not comparable. The four skin care interventions focused on 13 different care goals, mainly prevention of skin diseases, maintaining skin barrier function and improving (skin) health. We evaluated effects of skin care interventions using 57 different outcome domains; 39 of 57 were skin related and 18 were not. Mostly, laboratory or instrumental measurements were used. Key Messages Our scoping review identified four skin care interventions with a broad heterogeneity of product categories and application details. Studies in skin care interventions should include all relevant information about product category and application details to ensure comparability of study results. This would be helpful in developing recommendations for formal and informal caregivers. We identified 13 skin care goals. “Maintaining healthy skin/skin barrier function/skin barrier integrity”, “prevention of atopic dermatitis”, “cleansing” and “improving skin barrier function” were most often allocated to skin care interventions. There is substantial variability regarding outcome domains in skin care research. Our results support the need of developing core outcome sets in the field of skin care in healthy skin, especially in this age group of neonates and infants.
PubDate: Tue, 07 Feb 2023 10:33:57 +010
- MAPK/AP-1 signaling pathway is involved in the protection mechanism of
bone marrow mesenchymal stem cells-derived exosomes against
Ultraviolet-induced photoaging in human dermal fibroblasts-
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Abstract: Introduction: The role of bone marrow mesenchymal stem cells derived exosomes (BMSCs-exo) in skin photoaging was explored in human dermal fibroblasts (HDFs). The underlying mechanism was further explored.Methods: HDFs were exposed to UVB irradiation to establish the cell photodamage models. The cell viability, and levels of oxidative stress-related factors were tested. ELISA was done to detect TNF-α, IL-6 and IL-1β concentration. Western blot was applied for protein examination.Results: UVB treatment led to the inhibition of cell viability. But after BMSCs-exo addition, the inhibitory effect was returned in a dose manner. UVB exposure contributed to the increase of ROS and LDH, and the downregulation of SOD. In addition, excessive secretion of TNF-α, IL-6 and IL-1β was also detected in cells exposed to UVB. However, BMSCs-exo addition eliminated the effects of UVB on oxidative stress and inflammation in HDFs. BMSCs-exo inhibited MMP-1 and MMP-3 expression, but promoted collagen I expression. UVB radiation activated the MAPK/AP-1 signaling, manifested as the increase of p-p38, c-Jun and c-Fos protein levels, which was reversed by BMSCs-exo. As a p38 agonist, anisomycin (ANS) counteracted the effect of BMSCs-exo on HDFs viability, oxidative stress and inflammation.Conclusion: BMSCs-exo protected HDFs against UVB-induced inhibition of cell viability and the activation of cell oxidative stress and inflammation, which might be related to the inhibition of the MAPK/AP-1 signaling pathway.
PubDate: Mon, 06 Feb 2023 09:20:56 +010
- Permethrin steal effect by unmasked corneocytic keratin in topical therapy
of scabies-
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Abstract: Introduction: The use of epicutaneously applied permethrin in the treatment of common scabies is considered to be the first-line therapy. Due to increasing clinical treatment failure, the development of genetic resistance to permethrin in Sarcoptes scabiei var. hominis has been postulated. In addition, metabolic resistance and pharmacokinetic limitations by parasitic digestion and reactive thickening of stratum corneum are suspected to cause a reduction in cutaneous bioavailability. Methods: Since lipophilic permethrin is known to form hydrophobic interactions with proteins via van der Waals interactions, a similar interaction was assumed and investigated for permethrin and the protein keratin. Using keratin particles extracted from animal material, a model for hyperkeratotic and parasitic digested scabies skin was developed. Using fluorescence-labeled keratin and ³H-permethrin, their interaction potential was validated by loading and unloading experiments. Additionally, the impact of keratin to permethrin penetration was investigated based on an in vitro model using Franz diffusion cells.Results: For the first time, keratin particles were introduced as a model for dyskeratotic skin, as we were able to show, the keratin particles´ interaction potential with permethrin but no penetration behavior into the stratum corneum. Moreover, comparative penetration experiments of a reference formulation with and without added keratin or keratin-adherent permethrin showed that keratin causes a steal effect for permethrin, leading to a relevant reduction in cutaneous bioavailability in the target compartment. Conclusion: The results provide further evidence for a relevant pharmacokinetic influencing factor in the epicutaneous application of permethrin and a rationale for the necessity of keratolytic pretreatment in hyperkeratotic skin for the effective use of topical permethrin application in scabies.
PubDate: Mon, 30 Jan 2023 14:47:43 +010
- Application of topical Sandalore® increases epidermal dermcidin synthesis
in organ-cultured human skin ex vivo.-
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Abstract: Introduction: Several olfactory receptors (ORs) are expressed in human skin, where they regulate skin pigmentation, barrier function, wound healing, and hair growth. Previously, we found that the selective activation of OR family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant, Sandalore®, differentially stimulates the expression of antimicrobial peptides (AMPs) in human scalp hair follicle epithelium ex vivo. As OR2AT4 is also expressed by epidermal keratinocytes, we hypothesized that it may modulate intraepidermal AMP synthesis, thereby contributing to skin microbiome management.Methods: We investigated this hypothesis in organ-cultured human skin in presence of Sandalore® and antibiotics and evaluated epidermal production of two AMPs, LL37 (cathelicidin) and dermcidin (DCD), as well as OR2AT4, by quantitative immunohistomorphometry. Moreover, we quantified DCD secretion into the culture medium by ELISA, and studied the effect of culture medium on selected bacterial and fungal strains.Results: Topical application of Sandalore® to organ-cultured human skin increased OR2AT4 protein expression, number of DCD-positive intraepidermal cells, and DCD secretion into culture media, without significantly affecting epidermal LL37 expression. In line with the significantly increased secretion of DCD into the culture medium, we demonstrated, in a spectrophotometric assay, that application of conditioned media from Sandalore®-treated skin promotes Staphylococcus epidermidis, Malassezia restricta and, minimally, Cutibacterium acnes and inhibits Staphylococcus aureus growth.
PubDate: Thu, 26 Jan 2023 13:25:42 +010
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