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Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin
Abstract
Magnesium salts, the prevalent minerals in Dead Sea water, are known to exhibit favorable effects in inflammatory diseases. We examined the efficacy of bathing atopic subjects in a salt rich in magnesium chloride from deep layers of the Dead Sea (Mavena(R) Dermaline Mg(46) Dead Sea salt, Mavena AG, Belp, Switzerland). Volunteers with atopic dry skin submerged one forearm for 15 min in a bath solution containing 5% Dead Sea salt. The second arm was submerged in tap water as control. Before the study and at weeks 1-6, transepidermal water loss (TEWL), skin hydration, skin roughness, and skin redness were determined. We found one subgroup with a normal and one subgroup with an elevated TEWL before the study. Bathing in the Dead Sea salt solution significantly improved skin barrier function compared with the tap water-treated control forearm in the subgroup with elevated basal TEWL. Skin hydration was enhanced on the forearm treated with the Dead Sea salt in each group, which means the treatment moisturized the skin. Skin roughness and redness of the skin as a marker for inflammation were significantly reduced after bathing in the salt solution. This demonstrates that bathing in the salt solution was well tolerated, improved skin barrier function, enhanced stratum corneum hydration, and reduced skin roughness and inflammation. We suggest that the favorable effects of bathing in the Dead Sea salt solution are most likely related to the high magnesium content. Magnesium salts are known to bind water, influence epidermal proliferation and differentiation, and enhance permeability barrier repair.
... However, after applying the exclusion criteria, particularly the publication year cutoff (1980) to focus on more recent and relevant data, only 158 studies remained (refer to Fig. 1 for a graphical report of the article selection process). Among these, 16 studies met the full PICOS criteria and were deemed eligible for inclusion in this review (Nissen et al. 1998;Cohen et al. 2005Cohen et al. , 2008Proksch et al. 2005;Zijlstra et al. 2005Zijlstra et al. , 2007Harari et al. 2007;de Andrade et al. 2008;Ben-Amitai and David 2009;Staalesen Strumse et al. 2011;Czarnowicki et al. 2011;Wahl et al. 2015;Emmanuel et al. 2020Emmanuel et al. , 2022Emmanuel et al. , 2024Marsakova et al. 2020). In particular, two of these studies involved the same cohort of patients but focused on different clinical outcomes, highlighting various aspects of treatment efficacy (Emmanuel et al. 2020(Emmanuel et al. , 2022. ...
... In the case of atopic dermatitis, climatotherapy at the Dead Sea proved to be a highly effective intervention, particularly in pediatric populations (Proksch et al. 2005;Marsakova et al. 2020). In a Randomized Controlled Trial (RCT) involving children, the SCORAD score, a clinical tool used to assess disease severity, improved by 87.5% after four weeks of treatment, a similar improvement compared to the control group using steroid medications (Marsakova et al. 2020). ...
... In a Randomized Controlled Trial (RCT) involving children, the SCORAD score, a clinical tool used to assess disease severity, improved by 87.5% after four weeks of treatment, a similar improvement compared to the control group using steroid medications (Marsakova et al. 2020). For adults undergoing balneotherapy with Dead Sea salts, the therapy led to reduced transepidermal water loss and skin inflammation (Proksch et al. 2005). These results point to significant improvements in skin barrier function and symptom management for atopic dermatitis patients. ...
Thalassotherapy refers to the therapeutic use of controlled exposure to marine environments and their natural elements for health promotion. This review aims to summarize evidence-based clinical applications of thalassotherapy. A narrative review was conducted, with PubMed searched in September 2024 for clinical studies evaluating the efficacy of thalassotherapy. Relevant evidence was summarized and critically analyzed. A total of 566 articles were identified, of which 16 studies met the inclusion criteria. Thalassotherapy was primarily studied for its effects on skin disorders, including psoriasis, atopic dermatitis, and vitiligo, as well as rheumatic conditions like fibromyalgia and ankylosing spondylitis. The intervention showed significant improvements in disease severity and patient quality of life, with the strongest evidence seen in psoriasis and fibromyalgia treatment. Thalassotherapy appears beneficial for symptom relief in several conditions, particularly skin and rheumatic disorders. However, further research is needed to quantify its effect size, evaluate long-term benefits, assess potential risks, and identify factors that may influence treatment outcomes.
... Some destinations also specialize in alternative and complementary therapies such as acupuncture, Ayurveda, or traditional Chinese medicine. Developed countries with high quality healthcare infrastructure and advanced technologies attract individuals seeking specialized treatments (Pessot et al., 2021). ...
... It helps maintain skin moisture, reducing dryness and flaking associated with psoriasis plaques. Furthermore, magnesium's anti-inflammatory properties may help soothe irritated skin, providing relief from the discomfort of psoriasis (Ozler, 2003;Palmisano et al., 2024;Pessot et al., 2021). ...
... Beyond experimental studies, numerous case reports and anecdotal evidence support the use of hydrotherapy and mineral waters for the relief of psoriasis symptoms. Patients treated in areas with natural thermal or mineral springs often report reductions in itching, scaling, and inflammation associated with psoriasis (Proksch et al., 2005). The scientific evidence for the use of hydrotherapy and mineral waters in the treatment of psoriasis underlines the potential of these natural resources as complementary therapies. ...
... Ionic components derived from natural products, including hot spring water and deep sea water, have been used to promote health and beauty. In fact, studies have reported that treatment with hot spring water or deep sea water containing various ions prevents inflammation and improves the barrier function in atopic dermatitis and psoriasis (Hodak et al. 2003;Proksch et al. 2005;Chun et al. 2017;Lee et al. 2018). SE is included as a cosmetic ingredient in various cosmetic products, such as lotions and creams. ...
... Uchino et al. reported increased cholesterol sulfate in the skin of patients with dry skin and psoriasis (Uchino et al. 2020;Uchino et al. 2023). Studies have also reported that treatment with hot spring water or deep sea water containing various ions reduced inflammation and improved the barrier function in atopic dermatitis and psoriasis (Hodak et al. 2003;Proksch et al. 2005;Chun et al. 2017;Lee et al. 2018). The normalization of cholesterol content through the application of various ions may also be a factor in improving barrier function. ...
... Because SE contains a variety of divalent ions, these divalent ions may have caused misrecognition and promoted the expression of MgtE, which promoted Cer synthesis. Furthermore, it is often reported that calcium/ magnesium ratios recovery skin barrier function, and they might be due to enhanced lipid synthesis (Proksch et al. 2005;Lee et al. 2018;Denda et al. 1999). Therefore, the ion balance of SE may have contributed to changes in lipid composition. ...
Corneocytes and intercellular lipids form the stratum corneum. The content and composition of intercellular lipids in the stratum corneum significantly affect skin barrier function. The purpose of this study was to demonstrate the effect of Shotokuseki extract (SE) on intercellular lipid production and metabolism in human three-dimensional cultured human epidermis. SE or ion mixtures containing five common ions were applied to three-dimensional cultured human epidermis for 2–8 days for each assay. The mRNA expression levels of epidermal differentiation markers and lipid metabolism genes were quantified by real-time PCR. After extraction of lipids from the epidermis, ceramide, sphingosine, free fatty acids, and cholesterol were quantified by LC-MS/MS, GC-MS, or HPLC. The results showed that the application of SE increased the gene expression levels of epidermal differentiation markers keratin10 and transglutaminase. Elongation of very long-chain fatty acids protein 3, serine palmitoyl transferase, ceramide synthase 3, and acid ceramidase mRNA expression levels increased and fatty acid synthase mRNA expression decreased. The content of each lipid, [EOS] ceramide decreased and total sphingosine content increased on day 4. On day 8 of application, ceramide [NDS], [NP], and [EODS] increased and total free fatty acid content decreased. These results show that SE alters the lipid composition of the epidermis, increasing ceramides and decreasing free fatty acids in the epidermis. The composition of the ions in the SE may be responsible for the changes in lipid composition. These behaviors were different from those observed when the ion mixture was applied.
Graphical abstract
... Several studies have shown that magnesium can be a useful tool against various skin disorders. For example, it has been reported that the topical application of a magnesium-rich Dead Sea salt solution increased the water content in the skin of patients with atopic dry skin [11] and that the topical application of magnesium salt improved skin barrier function in mice [12]. Recently, we have revealed that administration of magnesium sulfate, which is commonly used as a laxative, increases AQP3 expression levels in the colon and that this increase plays an important role in laxative activity [13,14]. ...
... It has been reported that the addition of 10 mM magnesium compounds to HaCaT cells attenuates ultraviolet-B-induced damage [15]. It has also been reported that bathing containing magnesium compounds at a concentration of about 50 mM improves skin barrier function and dry skin in patients with atopic dermatitis [11]. Based on the above, in this study, the concentrations of magnesium compound added to HaCaT cells were set at 10 mM and 25 mM. ...
... Magnesium compounds have been reported to increase skin hydration and improve skin barrier function [11,12]. In this study, we analyzed the efect of magnesium on improving skin function, focusing on AQP3 expression in the skin. ...
Several studies have shown that magnesium can be a useful tool in preventing various skin disorders. However, the mechanism remains unclear. In this study, we analyzed the mechanism by which magnesium improves skin function, focusing on the water channel aquaporin-3 (AQP3), which is a cutaneous functional molecule. Magnesium compounds (magnesium acetate, magnesium chloride, magnesium sulfate, and magnesium lactate) were added to human epidermal keratinocyte HaCaT cells, and the mRNA and protein expression levels of AQP3 were analyzed. We also investigated the mechanism by which magnesium acetate regulates AQP3 expression. Several magnesium compounds were individually added to HaCaT cells, and 6 hours later, the AQP3 mRNA expression level in the treated cells was significantly increased compared to that in the control cells. Among the magnesium compounds, magnesium acetate had a strong effect and markedly increased the AQP3 mRNA expression level by approximately 3.5 times and the protein expression level by approximately 3 times. Magnesium acetate also enhanced the phosphorylation of cAMP response element-binding protein (CREB), which is involved in AQP3 transcription. Furthermore, the increase in AQP3 expression levels induced by magnesium acetate was suppressed by treatment with the protein kinase A (PKA) inhibitor H-89. Magnesium compounds increased the expression level of AQP3 in epidermal keratinocytes and may have a skin-moisturizing effect. The magnesium-induced phosphorylation of CREB may be associated with the activation of the cAMP/PKA pathway. Overall, magnesium compounds may be useful for the prevention and treatment of age-associated xeroderma.
... Penelitian lain yang mempelajari tentang efektivitas mineral pada perbaikan sawar kulit, termasuk pada penyakit kulit kronis telah banyak dilakukan di beberapa negara di Eropa dengan memanfaatkan mineral yang bersumber dari air laut mati. 24,25 Penelitian yang dilakukan oleh Paravina, dkk. di Serbia pada tahun 1914 menjelaskan secara luas mengenai efek balneoterapi pada pasien psoriasis. ...
... Beberapa perusahaan kosmetik di dunia telah membuat sebuah produk yang mengandung garam mineral, di mana produk tersebut tidak hanya bersifat sebagai pelembap tetapi juga dapat mengurangi kemerahan dan gatal. 25 Produk yang mengandung garam mineral tersebut antara lain berupa garam mandi, masker, dan air mineral yang telah dikemas dalam tabung spray sehingga lebih mudah digunakan. 37 Bahan-bahan yang digunakan untuk produk tersebut diambil langsung dari sumbernya dengan menggunakan kemasan khusus disertai proses sterilisasi, sehingga tidak mengurangi kandungan mineral yang terkandung. ...
... Beberapa produk yang berbentuk krim maupun gel dengan kandungan mineral terkadang diberikan tambahan zat aktif lainnya. 25 Produk yang telah banyak beredar di Indonesia antara lain Avene ® , Evian ® , La Roche-Posay ® . ...
Psoriasis merupakan penyakit inflamasi kronis residif dengan beberapa faktor risiko yang memengaruhi antara lain genetik, sistem imunitas, lingkungan serta hormonal. Lesi kulit psoriasis berupa plak eritematosa berbatas tegas dengan skuama tebal berlapis yang berwarna keputihan. Tata laksana psoriasis bervariasi tergantung dari derajat keparahan penyakit dan dapat berupa penggunaan obat topikal, sistemik, terapi sinar maupun terapi dengan menggunakan bahan-bahan alami seperti mineral dan balneoterapi. Balneoterapi dapat digunakan sebagai terapi tambahan pada psoriasis karena efektivitasnya terhadap perbaikan lesi psoriasis terutama tipe plak. Balneoterapi adalah teknik pengobatan tradisional dengan cara mandi, minum atau inhalasi menggunakan air yang mengandung mineral dan dapat menggunakan sumber mineral seperti air mineral, lumpur yang mengandung mineral (peloid) dan gas alam yang berasal dari mata air alami. Balneoterapi dapat mengurangi ketebalan stratum korneum dan lusidum, menurunkan jumlah limfosit, histiosit, granulosit dan eosinofil, meningkatkan permeabilitas kulit, mengurangi inflamasi, memperbaiki mikrosirkulasi serta sistem imun kulit serta dapat menurunkan cytokine proinflamasi pada penyakit psoriasis. Artikel ini bertujuan untuk membahas efektivitas modalitas balneoterapi sebagai terapi tambahan pada psoriasis sehingga dapat mempercepat terjadinya perbaikan klinis dan mengurangi terjadinya kekambuhan penyakit.
... 1,3,5 In this study, the MN patch was composed of magnesium metal, which is well known to play a beneficial role in the skin. [14][15][16] The magnesium ion plays a role in increasing skin hydration, ...
... 17,18 There also have been several reports of topical agents including magnesium ion regarding favorable effects on different types of dermatitis including diaper dermatitis, contact dermatitis, and atopic dermatitis. 15,19,20 On the basis of previous studies, [14][15][16][17][18][19][20] ...
... 17,18 There also have been several reports of topical agents including magnesium ion regarding favorable effects on different types of dermatitis including diaper dermatitis, contact dermatitis, and atopic dermatitis. 15,19,20 On the basis of previous studies, [14][15][16][17][18][19][20] ...
Microneedling is a common cosmetic procedure for improvement of wrinkles, acne, scars, and other conditions. Various microneedle (MN) patches have been developed as home care therapy for wrinkles and skin texture. Most of them are made of soluble and absorbable needles. To evaluate the efficacy and safety of non‐absorbable magnesium (Mg) MN patches on under‐eye wrinkles. A total of 20 subjects aged 27 to 58 years was enrolled in the study. The subjects applied Mg MN patches on the under‐eye wrinkle area for one to two hours every other night for 12 weeks. The evaluation comprised grading by clinicians, measuring the wrinkle index with a facial analyzer, and measuring the dermal thickness of the under‐eye area with ultrasonography. Any adverse events and discomfort were addressed during the study. The application of Mg MN patches on under‐eye areas showed improvements in under‐eye grading scale, wrinkle index, and dermal thickness after 12 weeks. The mean grading scale significantly improved after eight weeks of application (p < 0.01). The wrinkle index showed significant improvement after 12 weeks on the right under‐eye area (p < 0.05). The dermal thickness of the under‐eye area tended to increase, but no statistically significant changes were observed. Non‐absorbable Mg MN patches can be used for under‐eye wrinkles with minimal discomfort. This article is protected by copyright. All rights reserved.
... When hypersaline solutions are applied on skin, MIOS affects the modulation of cell-cycle dynamics. This is evident in reduced expression levels of inflammatory cytokines and in altered cell proliferation and differentiation rates [13] [15]. Specific external ion levels, mainly magnesium, calcium, potassium, and bromide, have been shown to affect cell proliferation and differentiation [13] [15] [16] [17] [18]. ...
... This is evident in reduced expression levels of inflammatory cytokines and in altered cell proliferation and differentiation rates [13] [15]. Specific external ion levels, mainly magnesium, calcium, potassium, and bromide, have been shown to affect cell proliferation and differentiation [13] [15] [16] [17] [18]. ...
... A particular case of MIOS's beneficial effect on human skin, is the topical exposure to Dead Sea minerals. The Dead Sea contains high levels of magnesium, calcium, and bromide ions and is clinically proven for its beneficial effects on several skin diseases [15] [21] [22]. Although these effects have been thoroughly studied on patients with skin diseases, the mechanism of MIOS involved as a key generating step for clinical efficacy, is not fully understood. ...
... However, evidence indicates that water bathing alone or in conjunction with other therapies benefts AD. For example, signifcant reductions in the transepidermal water loss rate (TEWL), skin roughness, and redness were observed in subjects who submerged their forearm in water solution, containing 5% dead sea salt, at 38°C-42°C for 15 min daily for 6 weeks, while immersion of the forearm in tap water did not change the TEWL signifcantly (p < 0.05) [36]. In addition, stratum corneum hydration levels were also increased by immersion of the forearm into the salted water (p < 0.05 vs. tap water). ...
... In a murine model of AD, immersion of mice in mineral water at 37°C-39°C daily for 2 weeks induced a more remarkable reduction in the TEWL than distilled water (p < 0.05 vs. distilled water) [31]. In AD patients, submersion of the forearm into water containing 5% deep sea salt (high magnesium content), but not into tap water, at 38°C-42°C daily for 6 weeks lowered the TEWL by 19%, while increasing stratum corneum hydration levels by 14% [36]. Bathing with hydrogen water 30 min once daily for 4 weeks signifcantly lowered the TEWL (p < 0.05), with a further reduction at 8 weeks (p < 0.001), whereas the TEWL was increased over the 8 weeks on the unmerged body site [48]. ...
Atopic dermatitis (AD) is a common skin disorder. Although a wide range of therapeutic regimens are available, they have some limitations, including high medical costs. However, evidence suggests that adjuvant regimens such as water bathing are inexpensive and effective approaches for the management of AD. Bathing with either tap water or seawater alone can improve AD symptoms and signs. Combination of water bathing with topic emollient or corticosteroids can synergically alleviate AD. The underlying mechanisms by which water bathing benefits AD include improvements in epidermal function, inhibition of mast cell and Langerhans cell function, reductions in serine protease expression and activity, inhibition of cytokine expression, and upregulation of expression levels of antioxidant enzymes, as well as antimicrobial peptides. In this review, we summarize the effects of water bathing on AD in both humans and murine models as well as the underlying mechanisms.
... In their study results, they emphasised the beneficial effects of balneotherapy in improving psoriasis symptoms and attributed these effects to the high mineral content of the waters used in the treatment . Furthermore, Proksch et al (2005) investigated the skin barrier repair properties of saltwater bathing and found significant improvements in skin condition and hydration, which are crucial for managing psoriasis symptoms. Beyond experimental studies, numerous case reports and anecdotal evidence support the use of hydrotherapy and mineral waters for the relief of psoriasis symptoms. ...
... Beyond experimental studies, numerous case reports and anecdotal evidence support the use of hydrotherapy and mineral waters for the relief of psoriasis symptoms. Patients treated in areas with natural thermal or mineral springs often report reductions in itching, scaling, and inflammation associated with psoriasis (Proksch et al., 2005). The scientific evidence for the use of hydrotherapy and mineral waters in the treatment of psoriasis underlines the potential of these natural resources as complementary therapies. ...
Psoriasis, an autoimmune and chronic inflammatory skin condition affecting
2-3% of the global population, is characterized by erythematous, scaly plaques,
with its aetiology remaining partially elusive. This disease significantly impacts
patients' quality of life and is associated with various comorbid conditions,
including cardiovascular diseases, diabetes, and psoriatic arthritis, yet lacks a
definitive, long-term cure. The recurrence of psoriasis and its variable clinical
manifestations have led clinicians to seek alternative treatments, with geothermal
and hydrotherapies emerging as supplementary options within health tourism
alongside conventional treatments. Turkey is known for its abundant thermal and
mineral waters, with temperatures ranging from 20°C to 102°C, particularly
around the Van province, where tectonic activity has given rise to waters rich in
ions such as Ca+2, Mg+2, and HCO3
-
. These waters are popularly believed to treat
skin conditions like psoriasis, eczema, atopic dermatitis, and rosacea. Despite
these beliefs, scientific research on the therapeutic benefits of Van's
hydrogeological and hydro mineral resources for skin diseases remains limited.
This study aims to scientifically assess the efficacy of Van's geothermal and
hydrobiological resources in treating psoriasis and explore the region's potential
as a health tourism destination for skin disease treatments. The significance of
investigating Van's subterranean and surface water resources extends beyond
health benefits, potentially positioning the region as a key site for healthy living
tourism and developmental growth.
Keywords: Psoriasis, Hydromineral Therapy, Thermal Therapy, Health
Tourism, Van Lake (Turkey)
... They are believed to be beneficial in dermatologic disease for removing the dead keratin material and improving the condition of impetiginized or ichthyotic skin. Different studies have highlighted the beneficial effects of dead sea salts [MgCl] in patients suffering from AD [77,78]. The Dead Seas' water has a very high salt content and is particularly rich in magnesium that binds to water, influencing epidermal proliferation and differentiation and reducing skin inflammation [77,79]. ...
... Different studies have highlighted the beneficial effects of dead sea salts [MgCl] in patients suffering from AD [77,78]. The Dead Seas' water has a very high salt content and is particularly rich in magnesium that binds to water, influencing epidermal proliferation and differentiation and reducing skin inflammation [77,79]. A study conducted on 1408 patients with AD showed complete clearance of skin lesions in 90% of patients after 4-6 weeks of therapy in the Dead Sea area [80]. ...
Atopic dermatitis is a chronic inflammatory skin disease. The treatment plays an important role in influencing the patients’ quality of life. The basic management consists of appropriate skin cleansing, including bathing and eventually using bathing additives. Recommendations regarding frequency and duration of bathing, water temperature and usefulness of bathing additives are widely different, often leading to confusion among patients. This review aims to give insights into the best bathing practices and the use of bathing additives in atopic dermatitis in children. Several bathing additives, including bleach baths, commercial baby cleansers, bath baby oils and bath salt, appear to be promising adjunctive therapies for atopic dermatitis due to their anti-inflammatory, anti-bacterial, anti-pruritus and skin barrier repair properties through different mechanisms of action. However, their efficacy and safety are not fully understood in some cases. The usefulness of other bath additives, such as acidic and more natural substances (green tea extracts, pine tar, sodium bicarbonate), is still under investigation. Further studies are needed to determine their optimal use to achieve clinical benefit safely.
... It is safe for everyday use, and the skin is patted dry after use. [7][8][9][10][11][12][13][14] Variations: ...
... In sharp contrast, no such study exists for Epsom salt bathing. [10][11][12][13] ...
Baths like Epsom salt bath, Oatmeal baths, Chlorhexidine Baths, Cindy's Bath, Psoralen Baths, Vinegar Baths, Soap Baths are underutilized in dermatology settings. Indeed the subject is poorly discussed in routine dermatology circles. Herein we discuss the types and uses of Baths, for bath is one such intervention which is not only cost effective but also highly efficacious since no other mode of drug delivery has the potential to reach so great a body surface area in such a small time.
... Eitan et al. compared the indexes before the study and at weeks 1-6, then they observed the elevation of basal TEWL and enhanced skin hydration. Meanwhile, the common skin inflammation markers, such as roughness and redness, were also significantly reduced after treatment [39]. By evaluating skin roughness using computer-aided laser profilometry, Ma'Or et al. investigated the cutaneous smoothing effects of three different liquid gels, one of which contained Dead Sea minerals. ...
... Clinically, the DSW also demonstrated an anti-inflammation effect on chronic inflammatory skin diseases, such as psoriasis or atopic dermatitis. As reported by Proksch [39], a magnesium-rich Dead Sea salt solution was applied to patients with atopic dry skin. A 15 min treatment in bath solution containing 5% Dead Sea salt for 6 weeks could greatly improve skin hydration, roughness, and reduce skin redness. ...
Applying natural mineral water to skin care is a popular tendency and many cosmetics products based on thermal spring water have been developed. The special location and environmental conditions provide Dead Sea water (DSW) with unique ion composition and concentrations, which bring comprehensive positive effects on skin health. This article reviews two potential action modes of DSW, and the biological function of DSW and its related complex in dermatology and skin care. Previous studies have proved the functions of skin moisturization, anti-inflammation, skin barrier repair, and anti-pollution. Especially, the anti-aging effect of DSW and related complexes can act in three different ways: keratinocyte rejuvenation, photo-protection, and cellular energy elevation. Additionally, the issues that need further investigation are also discussed. We hope that this review will help to improve the understanding of DSW and its related complex, and further contribute to product development in the skincare industry.
... Bathing in the Dead Sea waters (with an average concentration of 280 g/K) has been extensively studied: magnesium salts are known to bind water, influence epidermal proliferation and differentiation, and enhance permeability barrier repair [130]. In a study by Proksch et al. [131], immersion in magnesium-rich salt solutions from the Dead Sea was investigated (Mavena ® Dermaline Mg Dead Sea). The experiment consisted of 15 min bathing in a solution containing 5% Dead Sea salt daily for 6 weeks; transepidermal water loss (TEWL), stratum corneum hydration, and skin redness in atopic dry skin (xerosis) were measured, concluding that bathing with Mavena ® Dermaline Mg Dead Sea salt solution, owing to its high content of magnesium ions, enhanced stratum corneum hydration, improved skin barrier function and reduced skin roughness and inflammation [131]. ...
... In a study by Proksch et al. [131], immersion in magnesium-rich salt solutions from the Dead Sea was investigated (Mavena ® Dermaline Mg Dead Sea). The experiment consisted of 15 min bathing in a solution containing 5% Dead Sea salt daily for 6 weeks; transepidermal water loss (TEWL), stratum corneum hydration, and skin redness in atopic dry skin (xerosis) were measured, concluding that bathing with Mavena ® Dermaline Mg Dead Sea salt solution, owing to its high content of magnesium ions, enhanced stratum corneum hydration, improved skin barrier function and reduced skin roughness and inflammation [131]. ...
Cancer treatments have undergone significant advances in recent years, although they are not exempt from side effects, including skin toxicity. Different studies show that skin care for cancer patients can be effective in reducing sequelae such as inflammation, xerosis, skin rash, and radiodermatitis, among others. This is the reason why research is being carried out on the ingredients of cosmeceuticals for those indicated for oncological skin care. On the other hand, it is necessary to implement measures that improve the patient’s well-being and, therefore, thalassotherapy techniques and the marine environment could be an effective resource to achieve this goal. This article reviews the publications related to skin care after cancer treatment, including thalassotherapy techniques that can also contribute to well-being.
... Magnesium salts, the prevalent minerals in Dead Sea water, exhibit favorable effects on in lammatory diseases. Proksch, et al. examined the ef icacy of bathing atopic subjects in salt rich in magnesium chloride from deep layers of the Dead Sea [15]. Volunteers with atopic dry skin submerged one forearm for 15 min in a bath solution containing 5% Dead Sea salt. ...
... The authors reported that bathing in the salt solution was well tolerated, improved skin barrier function, the enhanced stratum corneum hydration, and reduced skin roughness and in lammation. Magnesium salts are known to bind water, in luence epidermal proliferation, and differentiation, and enhance permeability barrier repair [15]. ...
Introduction: Dead Sea Salt, rich in minerals and ionic compositions and low in Sodium Chloride (NaCl) has many reported unique properties that set it apart from other salts. Objectives: To evaluate the composition of Dead Sea Salt and assess its in vitro cytotoxicity, and efficacy against oral bacterial leukotoxins, oral endotoxins and oral glucan sucrase. Methods: The cytotoxicity was evaluated in an established cell line (solution at 5000 µg/mL of culture medium) using positive and negative control groups. The effect on oral bacterial leukotoxin (LtxA) and different concentrations of lipopolysaccharide and glucan sucrase was established at 24, 36, 48, 60, 72, 84, and 96 hours using the HPLC method (high-performance liquid chromatography). Results: The most predominant elements detected were the water of crystallization (H2O, water that is found in the crystalline framework of salt and which is not directly bonded ), magnesium chloride (MgCl2), potassium chloride (KCl), sodium chloride (NaCl), calcium chloride (CaCl2), bromide (Br -) and sulfates (SO4). In vitro, Dead Sea Salt presented no cytotoxicity and was highly effective against leukotoxin, endotoxin, and glucan sucrase enzyme. Conclusion and clinical significance: We believe that rinsing with Dead Sea Salt has the potential to contribute to the prevention of periodontal, peri-implant and dental disease and merits clinical research.
... The epidermal calcium gradient is attenuated or highly disturbed in aged or inflamed skin. Modification of the Ca 2+ /Mg 2+ ratio in favor of the latter mineral proves beneficial for recovery of the epidermal homeostasis, resulting in an optimal reparation of skin barrier, and may have impact on inflammatory skin diseases [72][73][74]. Acute abrogation of the extracellular calcium gradient by removal of the overlying SC barrier results in an instantaneous mobilization and excretion of the intracellular pool of lipids, aimed at the rapid restoration of tissue impermeability [75]. Many biochemical mechanisms, including those involved in keratinocyte differentiation, are regulated by calcium. ...
... Notably, inflammatory skin diseases such as psoriasis and atopic dermatitis were reported to benefit from such "cures" [135]. The mineral-rich solutes used contain principally magnesium and/or sulfur salts [74]. ...
As odd as it may seem at first glance, minerals, it is what we are all about…or nearly. Although life on Earth is carbon-based, several other elements present in the planet’s crust are involved in and often indispensable for functioning of living organisms. Many ions are essential, and others show supportive and accessory qualities. They are operative in the skin, supporting specific processes related to the particular situation of this organ at the interface with the environment. Skin bioenergetics, redox balance, epidermal barrier function, and dermal remodeling are amongst crucial activities guided by or taking advantage of mineral elements. Skin regenerative processes and skin ageing can be positively impacted by adequate accessibility, distribution, and balance of inorganic ions.
... Minerals such as sulfur, manganese, magnesium, and bicarbonate found in mineral springs and spring water are beneficial for skin conditions like AD [3,32]. Furthermore, the water from the Dead Sea, renowned for its rich mineral content, offers protection against UV-induced stress on human skin, enhances skin barrier function, increases skin hydration, and alleviates skin diseases, including inflammation associated with atopic dry skin [33,34]. More recently, research has demonstrated that deep sea water, which has a mineral composition similar to that of substances derived from the Dead Sea, helps protect the skin barrier, reduces inflammation, and improves various skin conditions, including AD [23,24]. ...
Background: Chronic pruritus and inflammatory skin lesions, characterized by high recurrence, are hallmarks of atopic dermatitis (AD). Despite its increasing prevalence, the development of therapeutic agents for AD remains limited. This study aimed to evaluate the therapeutic effects of deep sea minerals (DSMs) in mist and cream formulations on the development of AD-like skin lesions in NC/Nga mice exposed to either Dermatophagoides farinae body extract (Dfb) or 2,4-dinitrochlorobenzene (DNCB). Methods: To induce AD, 100 mg of Biostir AD cream containing crude Dfb or 200 µL of DNCB (1%) was topically applied to the dorsal skin of NC/Nga mice. Additionally, 200 µL of deep sea mineral mist (DSMM) and 10 mg of deep sea mineral cream (DSMC) were applied daily to the dorsal skin for 4 weeks. AD was assessed through visual observations, clinical scoring of skin severity, serological tests, and histological analysis. Results: Visual and clinical evaluations revealed that DSMs inhibited the formation of AD-like skin lesions. DSMs also significantly affected trans-epidermal water loss and erythema. Treatment with DSMs resulted in reduced serum levels of IgE, IFN-γ, and IL-4. Histological analysis indicated that DSMs decreased skin thickness. Immunostaining for the CD4 antigen demonstrated a reduced infiltration of CD4⁺ T cells, which drive the Th2 response in AD, following DSM treatment. Conclusions: In conclusion, the cream formulation of DSMs showed better results than the mist formulation. These results suggest that DSMs may be an effective treatment for AD-like skin lesions, especially in cream formulation.
... It also plays an important role in the absorption of saline and metal ions, favoring the excretion of toxic waste and some oxygenation of the tissues [49]. Additionally, magnesium salts, which are the prevailing minerals in Dead Sea water, are known to have anti-inflammatory activity, improving psoriasis, eczema, and other dermatological diseases [50][51][52], but also regenerative properties, moisturizing, smoothing, and anti-photoaging benefits [53,54]. ...
Peloids are mixtures of clays, sediments, or peat with mineral–medicinal water or seawater, or salt-lake water used in spa therapy for different treatments, including dermatological ones. The origin of peloids can be natural; that is, they are formed in situ at the place where the thermal water emerges or on the shores of the sea or salt lake, or they are prepared ad hoc from high-quality materials, such as clays or peat. Peloids are also used as cosmeceuticals in skin care to treat different skin disorders and/or conditions, such as psoriasis, eczema, and other scaly disorders, sensitive skin, and acne. This review reports all available scientific data concerning the effects and specific activities of peloids in skin care and cosmeceuticals, providing a better understanding of the clinical and cosmetic benefits. Finally, the safety and regulation of peloids are also discussed.
... It is known to have a combined effect on the human body: thermal, mechanical, chemical, immunological, and psychological (Rapolienė et al. 2016;Fioravanti et al. 2017;Gálvez et al. 2018;Kardes, Karagülle 2020;Ziemska et al. 2019). Natural mineral bathing is widely used for various medical conditions, including musculoskeletal, autoimmune, dermatological, digestive, pulmonary, cardiovascular, peripheral vascular pathologies and neurological disorders (Proksch et al. 2005;Korczak, Owczarek 2014;Rapoliene et al. 2016;Costantino et al. 2019;Antonelli et al. 2021;Gebretsadik 2023;Ushiko-shi-Nakayama et al. 2024). ...
Lithuania is rich in natural mineral waters and has a couple of centuries of history of using them for human health. The use of mineral water in medical SPAs has been popular since ancient times and continues to be important as a complement to modern medicine. Medical SPAs aim to achieve various health benefits by employing diverse types of mineral water with unique physicochemical compositions. The composition of mineral water used varies among different countries due to differences in hydrogeologic conditions, temperature, and chemical composition. While many countries have been investigating the properties of mineral water used for therapeutic purposes, scientifically grounded insights about the uniqueness of mineral water in Lithuanian medical SPAs are still limited. This study aims to investigate the physicochemical properties of mineral water used in Lithuanian medical SPAs and to evaluate their potential benefits for human health. To reach the research aim, a quantitative study was conducted in six of the most popular medical SPAs. The research results indicate that the mineral water used in medical SPAs is highly mineralized sodium chloride (salt) mineral water with significant calcium, magnesium, and sulphate levels. The mineral water is safe with regard to the presence of heavy metals. The tested mineral water could be used for the complementary treatment of nervous, rheumatic, skin, respiratory, cardiovascular, and metabolic disorders.
... Several studies have been performed with magnesium-rich TSW, mainly in the Dead Sea, where the content of magnesium salts is very high. Studies have shown that magnesium-rich Dead Sea salt solutions are able to improve skin barrier function, increase skin hydration, and reduce inflammation in atopic dermatitis [44]. When TSWs rich in calcium and magnesium are added to cosmetics formulations, the penetration of both cations is enhanced, and they can reach viable skin layers in a formulation-dependent manner [61]. ...
The role of thermal spring waters (TSWs) in the treatment of dermatological disease has been described by several authors, as have their benefits in treating certain skin conditions, among which atopic dermatitis, contact dermatitis, seborrhea, seborrheic dermatitis, psoriasis, acne, rosacea, and sensitive skin can be cited. It has been postulated that the mechanisms involved include chemical, thermal, mechanical, and immunological effects, and the chemical composition of thermal water is crucial in its skin effects. Thus, in this review, the effects of the different anions, cations, trace elements, and other compounds present in TSW were investigated, showing that the benefits of TSW can be mainly linked to its content of chloride, sulfate, and bicarbonate anions; calcium, sodium, and magnesium cations; and, among its trace elements, boron, selenium, strontium, manganese, and zinc, which are those with greater influence. Other compounds such as SiO2, sulfur anions, and CO2 can also exert specific effects. As a whole, the specific effects can be summarized as anti-inflammatory, antioxidant, wound healing improvement, skin hydration, and skin barrier recovery activities.
... Kalcio turintis vanduo gerina kraujo cirkuliaciją, širdies, raumenų veiklą, žaizdų gijimą, atpalaiduoja, nuskausmina, ramina, mažina kraujospūdį, gerina bronchų sekreciją, mažina alergijas, gali turėti įtakos hormonams, svorio mažinimui253,254,255 Magnio vonios turi vietinį ir bendrą poveikį: gerina odos būklę (veikia poras, didina elastingumą, skatina gijimą), mažina paburkimą, šalina skysčius, mažina kraujospūdį, nuovargį, galvos skausmus, raumenų įtampą ir skausmą, turi priešuždegiminį, nuskausminamąjį, atpalaiduojamąjį poveikį256,257,258 .CO 2 gydomasis poveikis pasireiškia, kai yra 0,75-1,4 g/l ištirpusių dujų. Šilumos patekimas į organizmą 1,4 karto didesnis nei gėlo vandens. ...
Stress has become a daily challenge worldwide, affecting people from various cultures and lifestyles. In the treatment of various somatic diseases, there is often a neglect of attention to reducing psychological stress. Assessing patients' mental states, implementing stress, anxiety, depression reduction strategies can be effective way to improve the patient's response to treatment. In the modern era of medical interventions, there is increasing recognition of the need for natural, holistic, and sustainable complementary treatment methods that reduce stress and improve overall health. The use of various natural resources - mineral waters and peloids - as therapeutic agents in many countries has ancient traditions, and their benefits in treating various diseases and conditions have been proven.
Balneoclimatology is important for the development of modern medicine due to its holistic, biopsychosocial, and economic perspectives, interdisciplinary and multidisciplinary value in integrative medicine. Due to the complexity and diversity of the biochemical composition of natural factors, the interrelationships of components, the multifaceted mechanism of action, and therapeutic effects, it is difficult to develop standardized treatment protocols that should have a place in the treatment guidelines for various diseases. With this publication, we aim to summarize existing balneoclimatological knowledge, overview scientific and practical methodologies, and provide practical recommendations that can be applied to improve the mental and physical health of individuals experiencing stress.
... Czarnowicki et al. (2010) изследват ефекта на климатотерапията край Мъртво море върху 436 пациента, като установяват значителна репигментация при над 80% от случаите и пълна репигментация при 3.9 % от тях (9). В допълнение Proksch et al. (2004) наблюдават значително подобряване на бариерната функция на кожата, повишена хидратация на роговия слой и намалена грапавост и възпаление при пациенти с атопичен дерматит (27). ...
The therapeutic use of seawater and sea resources dates back to ancient times. However, there is a need for in-depth study and summarization of the available clinical possibilities of modern thalassotherapy. Contact with sea water, sand and/or healing mud, methodical exposure to the sunlight, as well as environmental factors (atmosphere, temperature, humidity, wind, air pressure), are the basis of today‘s treatment procedures suitable for both children and geriatric patients. Due to the unique chemical composition of seawater, anti-inflammatory and immunomodulatory effects on the human body have been reported. Even short-term treatment by the sea can be used to relieve dermatological conditions such as psoriasis, atopic dermatitis, vitiligo, etc . In combination with physical exercises, thalassotherapy improves the symptoms of rheumatoid arthritis, rheumatic fibromyalgia, ankylosing spondylitis, psoriatic arthritis, and non-inflammatory joint processes. Separately, sea treatment is used to improve ventilatory performance in patients with bronchial asthma. The possibility of additional treatment for chronic inflammatory gynecological diseases, ovarian failure, neurovegetative disorders, menopausal symptoms and others has also been reported. The growing interest in natural treatments in recent years is an argument for conducting additional and even larger studies to explore the possibilities of modern thalassotherapy. Moreover, clinical data from recent years reinforce the potential for the development of maritime health tourism in Bulgaria.
... It was suggested that Mg as a divalent cation has anti-inflammatory and wound-restorative properties with inflammation declining topical application that can prevent tissue necrosis [11]. Also, its role in dermal hydration and reduction of skin redness is demonstrated [12]. ...
... Magnesium's absorption through the skin helps satisfy the body's minerals and reduces inflammation. 36 In addition, another research also claims that bathing with magnesium salt solution can reduce stress. 37 Apart from being used for bathing (Balneotherapy), there are various ways to use magnesium salts in OA sufferers as a complementary therapy, including for dietary use; one study found dietary magnesium could potentially prevent OA because magnesium deficiency can cause delays in cartilage and bone differentiation leading to OA. 15,38 Another study also found that intra-articular administration of magnesium and vitamin C can reduce joint damage and pain in OA. 17 The results of this study provide a new alternative for using magnesium sulfate as a therapy for OA sufferers, namely by using it topically, which is more practical. ...
Epsom salt as Osteoarthritis (OA) pain therapy has been limited to compresses, foot soaks, and baths. Many studies have examined Epsom salt to reduce pain, especially in OA, but Epsom salt formulation in gel form has never been tried, so it needs in-depth scientific evidence. This study aims to formulate an Epsom salt gel and test its effectiveness in reducing pain for OA patients. This is a true-experimental study with a completely randomized design. A total of 22 respondents with OA were included in the trial. In this study, each respondent received five treatments randomly (administration of pure gel (Negative control); Epsom salt gel with a concentration of 2%; 2.5%; 3%, and Diclofenac sodium (Positive control). Respondents' pain scale was assessed at the beginning and the end of each treatment as an outcome in this study. The data were analyzed using One-Way ANOVA and Tukey HSD. Epsom salt gels were successfully made with 2%, 2.5%, and 3% concentrations. The formulation results have met the physical test of gel preparation (organoleptic test, homogeneity, pH, and consistency). The results of clinical trials found that all Epsom salt gel concentrations effectively reduce OA pain levels (p<0.0001 vs. Control negative). Epsom salt gel with a concentration of 3% has a higher effectiveness level than other concentrations (p<0.0001). The effectiveness of Epsom salt gel with a concentration of 3% is almost equivalent to the oral drug diclofenac sodium. In conclusion, Epsom salt gel with a concentration of 3% as a topical drug has significantly reduced OA pain levels. Keywords: Epsom Salt Gels; Magnesium Sulfate; Pain; Osteoarthritis
... Magnesium ions are small, which favors their skin penetration. They are able to decrease inflammation, enhance hydration, affect keratinocytes migration, control epidermal differentiation, increase collagen synthesis and angiogenesis, and accelerate skin barrier repair [51,52]. Moreover, magnesium blocks N-methyl-D-aspartate receptors, reduces intracellular calcium ions, and, consequently, has an antinociceptive effect [49]. ...
Skin repair encompasses epidermal barrier repair and wound healing which involves multiple cellular and molecular stages. Therefore, many skin repair strategies have been proposed. In order to characterize the usage frequency of skin repair ingredients in cosmetics, medicines, and medical devices, commercialized in Portuguese pharmacies and parapharmacies, a comprehensive analysis of the products’ composition was performed. A total of 120 cosmetic products, collected from national pharmacies online platforms, 21 topical medicines, and 46 medical devices, collected from INFARMED database, were included in the study, revealing the top 10 most used skin repair ingredients in these categories. A critical review regarding the effectiveness of the top ingredients was performed and an in-depth analysis focused on the top three skin repair ingredients pursued. Results demonstrated that top three most used cosmetic ingredients were metal salts and oxides (78.3%), vitamin E and its derivatives (54.2%), and Centella asiatica (L.) Urb. extract and actives (35.8%). Regarding medicines, metal salts and oxides were also the most used (47.4%) followed by vitamin B5 and derivatives (23.8%), and vitamin A and derivatives (26.3%). Silicones and derivatives were the most common skin repair ingredients in medical devices (33%), followed by petrolatum and derivatives (22%) and alginate (15%). This work provides an overview of the most used skin repair ingredients, highlighting their different mechanisms of action, aiming to provide an up-to-date tool to support health professionals’ decisions.
... Zinc is a prominent cofactor for many enzymes (Table 8), especially those involved in wound healing [26][27][28][29]. The use of many zinc salts is FDA-approved for treating numerous conditions [27]. ...
Introduction: The science in aesthetic medicine continues to grow and expand exponentially. With improved science comes advanced clinical therapeutics that further benefits our patients. Physicians are seeking non-surgical technologies that are capable of safely treating all Fitzpatrick skin types while yielding meticulous results.
... Minerals are closely related to physiological actions and enzymatic reactions. In epidermal cells, calcium promotes differentiation [8] and regulates hyaluronic acid synthesis [9], magnesium improves barrier functions [10,11], and zinc promotes cell proliferation [12]. ...
The switch between keratinocyte proliferation and differentiation is regulated by extracellular calcium levels, requiring high concentrations (>1 mol/L) of extracellular calcium to induce differentiation. The Shotokuseki extract (SE) contains various ions such as calcium, but its effect on keratinocytes is unknown. This study focused on calcium-induced differentiation of keratinocytes and investigated the effects of simultaneous application of calcium and other ions on keratinocyte differentiation. The expression of differentiation markers increased when SE was added to a keratinocyte culture but not when only calcium was added at the same concentration present in SE. The calcium concentration in SE was found to be too low (0.01 mol/L) to induce differentiation of keratinocytes. In addition, the application of SE increased intracellular calcium concentration compared with calcium solution alone. Therefore, the induction of keratinocyte differentiation by SE is not calcium-dependent, or SE may alter the calcium sensitivity of keratinocytes. In our study, we found that simultaneous application of multiple ions and/or the application of trace ions may alter calcium sensitivity and the epidermal cell response. The function of ion transporters associated with these ions and the response of cells to ions depends largely on the balance among various ions and the function of trace ions.
... Low magnesium (Mg) levels are linked to increased inflammation [45]. For example, magnesium salts in Dead Sea water have a beneficial effect on inflammatory diseases [46]. Moreover, in 1966, the German chemist Bedouno Sanouni analyzed the sands near Siwa. ...
Background and Objectives: The most frequent cause of mortality in rheumatoid arthritis (RA) patients is cardiovascular disease (CVD). Inflammation, dyslipidemia, and decreased physical activity are some of the main risk factors for CVD. Siwan sand therapy is a type of traditional therapy used in Egypt to treat RA. The approach of this therapy depends on the experience of the healers. The aim of the current study was to compare the effects of three sessions of Siwan traditional therapy to five sessions on common CVD risk factors and physical function in rheumatoid arthritis patients. Materials and Methods: Thirty patients (9 male and 21 female) were assigned into two groups of equal size: group (A) received three sessions of Siwan traditional therapy in the form of a sand bath. Group (B) received the same form of therapy for five days. Erythrocyte sedimentation rate (ESR), lipid profile, atherogenic index of plasma (AIP), and a health assessment questionnaire (HAQ) were measured before and after treatment. Results: There was a significant increase above normal within group (A) for ESR (p = 0.001), triglycerides (TG; p = 0.015), total cholesterol (Tot-Chol; p = 0.0001), and low-density lipoprotein (LDL; p = 0.0001). However, there were no considerable differences in high-density lipoprotein (HDL; p = 0.106), very low-density lipoprotein (VLDL; p = 0.213), AIP (p = 0.648), and HAQ (p = 0.875). For the second group, there were significant changes within group B only in Tot-Chol (p = 0.0001), HDL (p = 0.0001), VLDL (p = 0.0001), AIP (p = 0.008), and HAQ (p = 0.014). There was a significant difference between both groups regarding HDL (p = 0.027), LDL (p = 0.005), AIP (p = 0.029), ESR (p = 0.016), and HAQ (p = 0.036). Conclusions: For RA patients, five days of Siwan traditional therapy caused significant changes regarding inflammation, Tot-Chol, LDL, HDL, AIP, and functional activity when compared to three days of Siwan hot sand therapy.
... WANG AND TANG -3 of 15 epidermal proliferation, differentiation, and skin barrier functions. 74,75 Sr ion has been reported to promote angiogenesis and suppress inflammation in skin wound treatments. [76][77][78] Cu ion is well-known for its significant role in angiogenesis by regulating the expression of proangiogenic factors such as vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) as well as the hypoxia-inducible factor (HIF-1α) to stimulate skin wound healing. ...
Regeneration of both anatomic and functional integrity of the skin tissues after injury represents a huge challenge considering the sophisticated healing process and variability of specific wounds. In the past decades, numerous efforts have been made to construct bioceramic‐based wound dressing materials with ion‐mediated multifunctionality for facilitating the healing process. In this review, the state‐of‐the‐art progress on bioceramic materials with ion‐mediated bioactivity for wound healing is summarized. Followed by a brief discussion on the bioceramic materials with ion‐mediated biological activities, the emerging bioceramic‐based materials are highlighted for wound healing applications owing to their ion‐mediated bioactivities, including anti‐infection function, angiogenic activity, improved skin appendage regeneration, antitumor effect, and so on. Finally, concluding remarks and future perspectives of bioceramic‐based wound dressing materials for clinical practice are briefly discussed.
... However, the binding between protein and ligands is generally affected by series of complex intermolecular interactions [33]. It has been reported that some salt ions play a significant role in decreasing skin inflammation [34], and salts component drugs can be used to treat several skin diseases, for example, salt water is useful to treat atopic dermatitis [35], therefore we study how salt ions affect the affinity of ligands to keratin at molecular scale, which is believed to be beneficial for both cosmetic and healthcare research. Nowadays, scientists are having an increasing interest in investigating the permeation efficiency of targeted small molecules [36][37][38]. ...
... However, the binding between protein and ligands is generally affected by series of complex intermolecular interactions [33]. It has been reported that some salt ions play a significant role in decreasing skin inflammation [34], and salts component drugs can be used to treat several skin diseases, for example, salt water is useful to treat atopic dermatitis [35], therefore we study how salt ions affect the affinity of ligands to keratin at molecular scale, which is believed to be beneficial for both cosmetic and healthcare research. Nowadays, scientists are having an increasing interest in investigating the permeation efficiency of targeted small molecules [36][37][38]. ...
... In the skin, Mg 2+ has functions such as acceleration of tissue repair [4] and suppression of inflammatory response [5]. Bathing in a Mg 2+ -rich Dead Sea salt solution induces several favorable effects, including the improvement of skin barrier function, enhancement of skin hydration, and reduction of inflammation in atopic dry skin [6]. These effects may be caused by the properties of Mg 2+ such as water binding capability. ...
Magnesium ions (Mg²⁺) have favorable effects such as the improvement of barrier function and the reduction of inflammation reaction in inflammatory skin diseases. However, its mechanisms have not been fully understood. Microarray analysis has shown that the gene expressions of polyamine synthases are upregulated by MgCl2 supplementation in human HaCaT keratinocytes. Here, we investigated the mechanism and function of polyamine production. The mRNA and protein levels of polyamine synthases were dose-dependently increased by MgCl2 supplementation, which were inhibited by U0126, a MEK inhibitor; CHIR-99021, a glycogen synthase kinase-3 (GSK3) inhibitor; and Naphthol AS-E, a cyclic AMP-response-element-binding protein (CREB) inhibitor. Similarly, reporter activities of polyamine synthases were suppressed by these inhibitors, suggesting that MEK, GSK3, and CREB are involved in the transcriptional regulation of polyamine synthases. Cell viability was reduced by ultraviolet B (UVB) exposure, which was rescued by MgCl2 supplementation. The UVB-induced elevation of reactive oxygen species was attenuated by MgCl2 supplementation, which was inhibited by cysteamine, a polyamine synthase inhibitor. Our data indicate that the expression levels of polyamine synthases are upregulated by MgCl2 supplementation mediated through the activation of the MEK/GSK3/CREB pathway. MgCl2 supplementation may be useful in reducing the UVB-induced oxidative stress in the skin.
... Long term exposure studies highlighted one potential beneficial effect of the seawater mineral extract on human keratinocyte cell biology in that it appreciably slowed the rate of keratinocyte cell proliferation up to concentrations of 0.8%, without inhibiting the process (especially at concentrations between 0.1% to 0.4%). skin hydration and reduced skin roughness, redness, and inflammation of the skin compared to tap water control (4). Both in vitro and in vivo studies reveal that magnesium ions significantly inhibit the antigen-presenting function of human epidermal Langerhans cells (5). ...
Nutrient poor diets implicated as major contributing factors to many inflammatory skin conditions have contributed to industries looking to the use of trace minerals, with limited success, due to the form, bioavailability and bio-functionality. This study utilises a unique free ion form of Deep Sea Magnesium and Trace Minerals harvested through organic, sustainable methods. These results challenge ideas fundamental to skin health and aging well. Utilising advanced in vitro dermal organotypic modelling of 3D human skin and employing integrative cell and molecular biology techniques we demonstrate Oriel Deep Sea Magnesium Mineral Complex to have potent cell health and functional benefits, including the regulation of genes involved in Dynamic Reciprocity and Tensegrity of the dermis, improving hydration and barrier function.
A wound, defined as a disruption in the continuity of the skin, is among the most common issues in the population and poses a significant burden on healthcare systems and economies worldwide. Despite the countless medical devices currently available to promote wound repair and skin regeneration, there is a growing demand for new skin devices that incorporate innovative biomaterials and advanced technologies. Bioglasses are biocompatible and bioactive materials capable of interacting with biological tissues. Due to their ability to promote fibroblast proliferation, angiogenesis, collagen production, and evade antibacterial activity, they have been suggested as key players in the skin regeneration process. Since their initial introduction, various compositions have been proposed depending on the clinical goal to be achieved. Recently, a novel bioglass composition named Bio_MS was found to exhibit significant bone regenerative potential. Given its peculiar composition characterized by strontium and magnesium, Bio_MS could also play a role in skin healing. In the present work, an innovative patch was designed by combining the attractive characteristics of Bio_MS with bioprinting technology. The regenerative potential of the Bio_MS patch was tested in an ex vivo cutaneous model using human skin in which an experimental wound was induced by sodium dodecyl sulfate incubation. After injury, the Bio_MS patch was able to restore skin architecture and enhance the epidermal barrier function. Additionally, the Bio_MS patch demonstrated therapeutic effects in both the epidermis and dermis, making it suitable not only for superficial lesions but also for deep wounds.
Seawater is a long-standing remedy against a number of skin or rheumatic conditions since ancient times, now popular in many countries, where spa, thalassotherapy and seawater pools have considerably boomed. Exposure to seawater and sunlight is an essential component of thalassotherapy, defined by any controlled interaction with marine environments and their natural elements, even in the absence of skin applications of algae, sands or muds. Seawater pools therefore offer the opportunity of thalassotherapy to patients unable to go the beach or during the winter months. The evidence from various studies seems to converge on combined exposure to solar radiation and seawater as a more effective approach than irradiation alone or bathing in freshwater followed by irradiation to reduce symptoms of inflammatory skin diseases or rheumatic conditions. An unwanted consequence of chlorine-based treatment of seawater is the formation of disinfection-by-products (DBPs) due to reactions of disinfectants with organic matter of anthropogenic origin released by bathers. Whilst chlorination of freshwater predominantly generates chlorinated DBPs, the prevailing species produced by chlorination of seawater pools are brominated DBPs, reportedly more genotoxic. However, despite greater toxicity of brominated DBPs, there is evidence that DBPs concentration in freshwater pools is significantly higher (probably due to the larger number of users) compared to seawater pools. Containing the number of bathers could therefore reduce the risk of exposure to DBPs in both types of pool. The outdoor location of pools can further contribute to reducing the risk of genotoxicity thanks to volatilization, airborne dispersion and photodegradation of some DBPs.
Background: Seborrheic and atopic dermatitis are common and chronic
inflammatory skin diseases. Conventional treatments are often ineffective
and can have significant side effects. Magnesium dead sea salt has a high
concentration of magnesium, and previous research shows its potential to
help improve skin conditions. Case presentation: Patients with chronic
seborrheic and atopic dermatitis were treated with topical 5% dead sea salt
magnesium for 4 days. Patients experienced significant improvement in their
symptoms. Conclusion. Dead Sea salt magnesium can be a safe and effective treatment for seborrheic and atopic dermatitis
Objective
External environmental stressors and internal factors have a significant impact on the skin, causing inflammation, aging, reduced immunity and other adverse responses. Dead Sea Water (DSW) is well known for its dermatological benefits and has been widely used in dermatological therapy and skin care for conditions such as psoriasis, atopic dermatitis and photoaging. However, the anti‐aging and rejuvenating effects of DSW and the related biological pathways involved, which have attracted increasing attention, are not fully understood. The aim of this study is to investigate the anti‐aging and rejuvenating effects of DSW and to explore the related potential biological mechanisms of DSW under different environmental conditions.
Methods
The effects of DSW were investigated using in vitro human dermal cells and reconstructed skin models. Extracellular matrix (ECM) components and the morphological changes at the dermal‐epidermal junction (DEJ) in a 3D human skin model were evaluated after DSW treatment. RNA sequencing (RNA‐seq) analysis of human dermal fibroblast models after DSW treatment was performed to explore the potential mechanisms of action of DSW under normal and UV stress conditions.
Results
The novel findings in this work present the biological functions of DSW, including procollagen‐1 and elastin secretion, hemidesmosome increase and the epidermal basal cell regeneration. In addition, GO, KEGG and Reactome analyses reveal the activation of pathways related to ion transmembrane transporter activity, ECM component biosynthesis, senescence‐associated secretory phenotype (SASP), DNA repair and autophagy, which are associated with the anti‐aging activities of DSW.
Conclusion
Our work provides new perspectives for understanding the anti‐aging and rejuvenating effects and mechanisms of DSW. The new findings also provide a theoretical basis for the further development of age‐related strategies.
Background
Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin condition that presents with symptoms of intense pruritus, dryness, and erythema. Dissatisfaction with first-line therapies for AD, the desire to avoid steroids, and the extreme cost of effective biologics have created a demand for alternative treatment options such as oral vitamins and nutritional supplements.
Objective
The purpose of this review was to assess the effectiveness of oral nutritional supplements, pre- and probiotics, and vitamin deficiencies and supplements on AD symptomology and clinical course.
Methods
We searched Scopus, PubMed, and MEDLINE (Ovid interface) for English-language articles published between 1993 and 2023. The final search was conducted on June 22, 2023. The search terms comprised the following: “(Atopic Dermatitis or Atopic Eczema) AND (supplement OR vitamin OR mineral OR micronutrients OR Fish Oil OR Omega Fatty Acid OR Probiotics OR Prebiotics OR apple cider vinegar OR collagen OR herbal OR fiber).”
Results
A total of 18 studies—3 (17%) evaluating vitamins, 4 (22%) evaluating herbal medicine compounds, 2 (11%) evaluating single-ingredient nutritional supplements, and 9 (50%) evaluating pre- and probiotics—involving 881 patients were included in this review.
Conclusions
Overall, there is weak evidence to support any one nutritional supplement intervention for the alleviation of AD symptoms. Multiple trials (4/18, 22%) showed promise for supplements such as Zemaphyte, kefir, and freeze-dried whey with Cuscuta campestris Yuncker extract. The most evidence was found on the effectiveness of probiotics on the clinical course of AD. Lactiplantibacillus plantarum, Ligilactobacillus salivarius, and Lactobacillus acidophilus specifically showed evidence of efficacy and safety across multiple studies (6/18, 33%). However, larger, more extensive randomized controlled trials are needed to determine the true effectiveness of these supplements on the broader population.
Trial Registration
PROSPERO CRD42023470596; https://tinyurl.com/4a9477u7
The utilization of materials in medical implants, serving as substitutes for non-functional biological structures, supporting damaged tissues, or reinforcing active organs, holds significant importance in modern healthcare, positively impacting the quality of life for millions of individuals worldwide. However, certain implants may only be required temporarily to aid in the healing process of diseased or injured tissues and tissue expansion. Biodegradable metals, including zinc (Zn), magnesium (Mg), iron, and others, present a new paradigm in the realm of implant materials. Ongoing research focuses on developing optimized materials that meet medical standards, encompassing controllable corrosion rates, sustained mechanical stability, and favorable biocompatibility. Achieving these objectives involves refining alloy compositions and tailoring processing techniques to carefully control microstructures and mechanical properties. Among the materials under investigation, Mg- and Zn-based biodegradable materials and their alloys demonstrate the ability to provide necessary support during tissue regeneration while gradually degrading over time. Furthermore, as essential elements in the human body, Mg and Zn offer additional benefits, including promoting wound healing, facilitating cell growth, and participating in gene generation while interacting with various vital biological functions. This review provides an overview of the physiological function and significance for human health of Mg and Zn and their usage as implants in tissue regeneration using tissue scaffolds. The scaffold qualities, such as biodegradation, mechanical characteristics, and biocompatibility, are also discussed.
Diaper Dermatitis (DD) is the most common skin disease in infants and children, and may cause problems such as restless, pain and sleep disorders. Stress can also develop on parents and caregivers due to their child's restlessness and illness. It is important to know the clinical findings of DD and to treat the disease before it progresses. In this review, factors, clinical findings, diagnosis, complications, prevention measurement and new treatment methods in DD was evaluated. Alternative treatment methods and treatment strategies are being developed for DD as a result of advances in technology and medicine. Protective and preventive methods are the first approach strategy in DD, and we think that it will be effective to provide training to parents before and after birth.
Anxiety disorders have become the number one mental health issue in developed countries. The number of people living with anxiety and depressive disorders rose significantly because of the COVID-19 pandemic. Although generally considered as safe and effective, the currently available anxiolytic therapy is responsible for numerous side effects and addiction. Therefore, there is an imperious demand for discovering more efficient and cheaper new groups of pharmaceuticals (“green anxiolytic”). There is a big number of research, studying plants containing coumarins as active compounds, especially those belonging to the Apiaceae family. Laboratory studies already suggest the anti-anxiety activity of various extracts of Angelica Archangelica. Therefore, the aim of our study was to obtain the methanolic extract of Angelica adzharica and evaluate the potential anxiolytic effect based on the zebrafish larvae model. According to our knowledge, this is the first report studying the anxiolytic effect of Angelica adzharica extract based on the zebrafish larvae.
Over the last decades, different compositions of bioactive glasses in various forms of nano/microparticles, fibers, and 3D scaffolds have been proposed as multifunctional therapeutic materials to induce biological responses in soft tissues, including skin wounds. The superiority of bioactive glasses over the other materials is the possibility of incorporating multiple biologically active elements such as cerium, cobalt, copper, gallium, selenium, silver, and zinc in their structure, which can target different stages of the wound healing process following the release of these therapeutic ions in the wound environment. Since no wound care approach is yet completely satisfying, diverse biomaterial‐based wound care approaches are already under development to address the unfulfilled clinical needs of patients with severe burn injuries and chronic wounds. In this regard, the use of bioactive glasses seems to be an effective approach in complementing the current role of polymeric biomaterials in wound healing applications. The purpose of this chapter is to focus on the application of bioactive glasses in the healing process and particularly their specific biological effects in the wound bed, which may facilitate the healing of hard‐to‐heal wounds.
Reconstruction of the microenvironment at the site of injury plays an important role in tissue regeneration and functional recovery. With calcium magnesium phosphate (MCPC) as a model, the effects of MCPC on the vascularization and neurotization in the process of wound regeneration were investigated. Herein, a series of MCPC/hydrogels with different concentrations (0–4%) of MCPC were synthesized. The results showed that MCPC could stimulate the migration behavior of vascular endothelial cells (HUVECs) and up-regulate the expression of VEGF and HIF-1α genes. Further in vivo results revealed that MCPC/hydrogels significantly improved wound healing and blood vessel formation. In addition, we demonstrated that MCPC/hydrogels could also largely accelerate the regeneration of nerves, which would finally contribute to wound healing due to the proper release of magnesium and calcium ions. This research also provides an insight toward the positive role of MCPC in vascular and nerve reconstruction during wound healing.
Dietary macro and trace minerals like magnesium, calcium, copper, zinc, nickel
and manganese are nutrients critical to human skin and general health, performance and welfare. Skin health and nutrition for immunity, cardiovascular, gastrointestinal and reproductive health, to name a few, depend on optimal macro and trace mineral nutrition. In recent years, magnesium is proving to be far and above the most important of these minerals, playing an important role in skin, hair and general health and wellbeing.
Background/aims: Topometry is one of the most relevant methods for biophysical research on skin in dermatologic and cosmetic science, because it relates very closely to the perceived quality of skin. Taking silicon replicas of skin sites under investigation and measuring those imprints with mechanical or optical profilometers is still the most frequently used method. Direct measurement of the topography of human skin in vivo by active image triangulation avoids the need to make replicas and seems to be a promising alternative.
Methods: The introduction of active image triangulation in conjunction with phase‐shift techniques in skin topometry enables a fast and non‐invasive measurement of the skin surface in vivo. The main attribute of the proposed system is the projection of a regular sinusoidal intensity pattern with a sophisticated digital projection device onto the surface of skin under a certain angle of incidence. The height information of the structured surface is coded in the distorted intensity pattern, which is recorded by an appropriate video technique.
Results: Successful in vivo measurements of selected body sites and measurements on scar, nevus, wound and wrinkles are presented in this paper. Furthermore, irritation of skin, influence of hydration of skin, and differences between youthful and elderly skin can be detected in the measurement results of the new optical system.
Conclusions: For measuring the topog raphy of human skin, active image triangulation is appropriate both for macrotopometry (nevus, scar, wound) and for microtopometry (casts, selected body sites). This new non‐contact technique allows dynamic measurements of alterations in skin topography as a consequence of certain treatments (e.g., application of ingredient, hydration of skin) without removal of corneocytes or scales. Optical three‐dimensional (3D) topometry using active image triangulation appears to offer a significant improvement in speed and flexibility, providing a fast and accurate analysis of skin surface topography.
Topical solvent treatment removes lipids from the stratum corneum leading to a marked increase in transepidermal water loss (TEWL). This disturbance stimulates a variety of metabolic changes in the epidermis leading to rapid repair of the barrier defect. Using an immersion system we explored the nature of the signal leading to barrier repair in intact mice. Initial experiments using hypotonic to hypertonic solutions showed that water transit per se was not the crucial signal. However, addition of calcium at concentrations as low as 0.01 mM inhibited barrier repair. Moreover, both verapamil and nifedipine, which block calcium transport into cells, prevented the calcium-induced inhibition of TEWL recovery. Additionally, trifluoroperazine or N-6-aminohexyl-5-chloro-1-naphthalenesulfonamide, which inhibit calmodulin, prevented the calcium-induced inhibition of TEWL recovery. Although these results suggest an important role for calcium in barrier homeostasis, calcium alone was only modestly effective in inhibiting TEWL recovery. Potassium alone (10 mM) and phosphate alone (5 mM) also produced a modest inhibition of barrier repair. Together, however, calcium and potassium produced a synergistic inhibition of barrier repair (control 50% recovery vs. calcium + potassium 0-11% recovery in 2.5 h). Furthermore, in addition to inhibiting TEWL recovery, calcium and potassium also prevented the characteristic increase in 3-hydroxy-3-glutaryl CoA reductase activity that occurs after barrier disruption. Finally, the return of lipids to the stratum corneum was also blocked by calcium and potassium. These results demonstrate that the repair of the epidermal permeability barrier after solvent disruption can be prevented by calcium, potassium, and phosphate. The repair process may be signalled by a decrease in the concentrations of these ions in the upper epidermis resulting from increased water flux leading to passive loss of these ions.
The influence of tap-water (TW) and salt solutions on the minimal erythema dose (MED) was investigated for normal human skin and uninvolved skin of psoriasis patients. MED (UVB) determinations on the forearm revealed that: (1) the MED definitely decreases whenever the arm is immersed in TW or NaCl solutions with a low concentration (4%) prior to UVB exposure, whereas almost saturated NaCl solution (26%), as well as locum Dead Sea water (LDSW), do not produce a change in the MED, and (2) the decrease in MED obtained by wetting the skin with TW was no longer present when the skin was allowed to dry for 20 min.
A decrease in water uptake by skin (in vivo) and by callus (in vitro) was found as the salt concentration of the external solution increased. It is proposed that water taken up by the skin plays an important role in the sensitivity of the skin to UVB exposure.
Bathing in TW or 4% NaCl prior to UVB exposure offered a slight to moderate improvement in psoriasis over UVB irradiation alone. Finally, it was shown that there is no obvious difference in clearance of the psoriatic skin between a bath in TW, 4% NaCl, or LDSW prior to UVB exposure.
To gain a better understanding of the interaction of the model detergent sodium lauryl sulfate (SLS) with the stratum corneum, we investigated systematically the ultrastructural changes of the epidermal barrier and the nucleated parts of the epidermis after the occluded application of different concentrations of SLS in human. Different application models were investigated. Two of the three irritation procedures (long duration exposure and the repetitive exposure for 3 d) provoked damage of the nucleated parts of the epidermis and alterations of the lower parts of the stratum corneum. Here, the extrusion and transformation of lamellar body derived lipids into lamellar lipid bilayers were disturbed; however, the upper portions of stratum corneum displayed intact intercellular lipid layers that contradict the long-standing belief that surfactants damage the skin by delipidization. Furthermore, we investigated ultrastructurally and by measurement of transepidermal water loss the influence and protective capacity of a lipophilic barrier cream on acute irritant contact dermatitis. The irritant contact dermatitis was induced by the standardized cumulative short application model with two SLS concentrations (0.5% and 0.75%). The cumulative type of exposure simulates daily living more realistically. Because most of the previous tests have been performed on the human forearm or back, we analyzed whether the pattern of response was similar on both sites. The back showed a higher level of irritant reaction, but the pattern of irritant response proved to be similar to the forearm. Application of the barrier cream before and during irritation showed a decrease of transepidermal water loss enhancement with 0.5% SLS by 58% (back) and 49% (arm) and after irritation with 0.75% SLS by 56% (back) and 43% (arm). Because the experimental result correlated with the clinical experience, the development of the cumulative short exposure model might help to predict and to discriminate the efficacy of barrier creams.
Using the crotonoil test, anti-inflammatory effects of magnesium chloride-containing ointments were compared with those of steroid-containing ointments. Our results: Magnesium-chloride-containing ointments can significantly inhibit the croton-oil-induced inflammation (15% magnesium chloride: 58.2% inhibition, p < 0.001; 7% magnesium chloride: 49.9% inhibition, p < 0.01). These ointments inhibit like a 0.5% hydrocortisone-containing ointment.
The epidermal permeability barrier resides in the stratum corneum (SC), a heterogeneous, two-compartment tissue. Whereas the cells (corneocytes) of the SC are lipid-depleted, they are embedded in a continuous, lipid-enriched extracellular matrix organized into characteristic, multilamellar membrane unit structures, which mediate barrier function (22). The formation of the permeability barrier is the goal of epidermal proliferation and differentiation, processes that begin in the basal layer. The quantitatively most important cell type of the epidermis, the keratinocyte, derives from stem cells, and en route to the SC it synthesizes specific basal (K5 and K14) and suprabasal (K1 and K10) keratins, as well as cornified envelope (CE)-associated proteins (20). The CE begins to form with the deposition and cross-linking of involucrin and envoplakin on the intracellular surface of the plasma membrane in the upper spinous and granular cell layers of the epidermis. The process begins at or near desmosomal sites, followed by the subjacent addition of elafin, small prolin-rich proteins, and loricrin. With cornification, the phospholipid-enriched plasma membrane disappears, followed by the formation of a ceramide-containing membrane bilayer (see below), which is covalently attached to involucrin, envoplakin, and periplakin moieties on the extracellular surface of the CE by ω-hydroxyester bonds (57).
At the Dead Sea spas, which are 400 m below sea level, both the ultraviolet radiation from the sun and the mineral-rich waters of the lake have special features. The separate influence of these two factors was studied in 81 patients with psoriasis. The condition was assessed during 4 weeks of treatment using the psoriasis area and severity index (PASI). In subjects who only bathed in Dead Sea water the improvement was 28%, in those who only sunbathed it was 73%, and in those who did both it was 83%. The main therapeutic factor was thus shown to be sun exposure, possibly enhanced by bathing in Dead Sea water. Similar degrees of improvement in spring, summer and autumn led to speculation about the optimum dose of solar radiation needed.
We have demonstrated recently that shifts in the concentrations of extracellular Mg++ and Ca++ occur during cutaneous injury in viva. These shifts correlate well with the timing of migration of various cell types involved in wound healing, including keratinocytes, In the present study, we examined the potential of such cation shifts to activate the keratinocyte migratory phenotype. In modified Boyden chamber migration assays, α2β1 integrin-mediated migration of human keratinocytes (HaCaT) on type I collagen was supported by Mg++ but not by Ca++ alone. Migration could be increased up to twofold, however, by using both cations in combination, as long as the Mg++ concentration was in the optimal range for migration in Mg++ only (1–3 mM) and Ca++ was present at concentrations of approximately 0.1–1 mM, Further examination of this divalent-cation-induced migratory keratinocyte phenotype demonstrated that, as Mg++ is elevated and Ca++ is reduced, mature E-cadherin and cell-cell contacts are reduced and the α2β1 integrin is redistributed from cell-cell contacts to the periphery. These in vitro observations corroborate what occurs in vivo at the keratinocyte migrating front during wound healing. Together these data suggest that changes in the concentrations of extracellular Mg++ and Ca++ can regulate the competitive interplay between Ca++-dependent E-cadherin-mediated and Mg++-dependent α2β1-integrin-mediated adhesion, promoting the development of an activated keratinocyte phenotype.
In previous studies we have shown that experimental permeability barrier disruption leads to an increase in epidermal lipid and DNA synthesis. Here we investigate whether barrier disruption also influences keratins and cornified envelope proteins as major structural keratinocyte proteins. Cutaneous barrier disruption was achieved in hairless mouse skin by treatments with acetone occlusion, sodium dodecyl sulfate, or tape-stripping. As a chronic model for barrier disruption, we used essential fatty acid deficient mice. Epidermal keratins were determined by one- and two-dimensional gel electrophoresis, immunoblots, and anti-keratin antibodies in biopsy samples. In addition, the expression of the cornified envelope proteins loricrin and involucrin after barrier disruption was determined by specific antibodies in human skin. Acute as well as chronic barrier disruption resulted in the induction of the expression of keratins K6, K16, and K17. Occlusion after acute disruption led to a slight reduction of keratin K6 and K16 expression. Expression of basal keratins K5 and K14 was reduced after both methods of barrier disruption. Suprabasal keratin K10 expression was increased after acute barrier disruption and K1 as well as K10 expression was increased after chronic barrier disruption. Loricrin expression in mouse and in human skin was unchanged after barrier disruption. In contrast, involucrin expression, which was restricted to the granular and upper spinous layers in normal human skin, showed an extension to the lower spinous layers 24 h after acetone treatment. In summary, our results document that acute or chronic barrier disruption leads to expression of keratins K6, K16, and K17 and to a premature expression of involucrin. We suggest that the coordinated regulation of lipid, DNA, keratin, and involucrin synthesis is critical for epidermal permeability barrier function.Keywords: loricrin
Rheinwald and Green's technique is currently the standard method for growing stratifying epidermal cell cultures. The serum free system developed in Ham's laboratory (MCDB 153) was designed to grow keratinocyte monolayers in clonogenic conditions. Our aim was to optimize conditions in serum-free MCDB 153 for culturing epidermal sheets from adult normal skin, and to assess the effect of extracellular calcium and temperature on proliferation and differentiation of cultured keratinocytes. Sixteen strains derived from plastic surgery specimens (mean age of donors 37 years; range 5–89) were used. Primary cultures were seeded at an optimal density of 8 × 104 cells/cm2 in primary cultures and 104 cells/cm2 in secondary cultures in complete medium including EGF, insulin, hydrocortisone and bovine pituitary extract, supplemented with isoleucine, tyrosine, methionine, phenylalanine, tryptophane and histidine.
The aim of the study was to assess the susceptibility of clinically normal skin to a standard irritant trauma under varying physiological and patophysiological conditions. Evaluation of skin responses to patch tests with sodium lauryl sulphate (SLS) was used for assessment of skin susceptibility. The following noninvasive measuring methods were used for evaluation of the skin before and after exposure to irritants: measurement of transepidermal water loss by an evaporimeter, measurement of electrical conductance by a hydrometer, measurement of skin blood flow by laser Doppler flowmetry, measurement of skin colour by a colorimeter and measurement of skin thickness by ultrasound A-scan. The studies were carried out on healthy volunteers and patients with eczema. In the first studies the standard irritant patch test for assessment of skin susceptibility was characterized and validated. SLS was chosen among other irritants because of its ability to penetrate and impair the skin barrier. The implications of use of different qualities of SLS was investigated. The applied noninvasive measuring methods were evaluated, and for quantification of SLS-induced skin damage measurement of TEWL was found to be the most sensitive method. Application of the standard test on clinically normal skin under varying physiological and patophysiological conditions lead to the following main results: Seasonal variation in skin susceptibility to SLS was found, with increased susceptibility in winter, when the hydration state of the stratum corneum was also found to be decreased. A variation in skin reactivity to SLS during the menstrual cycle was demonstrated, with an increased skin response at day 1 as compared to days 9-11 in the menstrual cycle. The presence of active eczema distant from the test site increased skin susceptibility to SLS, indicating a generalized hyperreactivity of the skin. Taking these sources of variation into account healthy volunteers and patients with hand eczema and atopic dermatits were studied and compared. In healthy volunteers increased baseline TEWL and increased light reflection from the skin, interpreted as "fair" skin, was found to be associated with increased susceptibility to SLS. Hand eczema patients were found to have fairer and thinner skin than matched controls. Increased susceptibility to SLS was found only in patients with acute eczema. Patients with atopic dermatitis had increased baseline TEWL as well as increased skin susceptibility as compared to controls. Skin susceptibility is thus influenced by individual- as well as environment-related factors. Knowledge of determinants of skin susceptibility may be useful for the identification of high-risk subjects for development of irritant contact dermatitis, and may help to prevent the formation of the disease.
The relationship between the in vivo irritation potential of sodium lauryl sulfate (SLS) and linear alkyl benzene sulfonate (LAS) and the ability of these two surfactants to remove lipid from the stratum corneum (SC) in vitro were investigated. Either surfactant removes detectable levels of lipids only above its critical micelle concentration (CMC). At high concentrations the surfactants removed only very small amounts of cholesterol, free fatty acid, the esters of those materials, and possibly squalene. SLS and LAS have been shown, below the CMC, to bind to and irritate the SC. Thus, clinical irritation provoked by SLS or LAS is unlikely to be directly linked with extraction of SC lipid. The milder forms of irritation--dryness, tightness, roughness--may involve both surfactant binding to and denaturation of keratin as well as disruption of lipid. Our findings challenge earlier assumptions that surfactants' degreasing of the SC is involved in the induction of erythema.
Water containing high concentrations of magnesium ions (e.g. Dead Sea water) is effective in the treatment of inflammatory skin diseases. Therefore, we examined the influence of Mg2+ on inflammation in allergic contact dermatitis induced by 1-chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Animals challenged with 0.125% DNCB in the presence of magnesium chloride (28% and 14%) demonstrated significantly less pronounced contact dermatitis (ear swelling) than did animals challenged with DNCB alone (p less than 0.001 and p less than 0.01). In mice challenged with DNCB in combination with sodium chloride (14%) there was no statistically significant difference in the degree of ear swelling. These results were borne out in 5 patients known to be allergic to nickel, in whom magnesium chloride but not sodium chloride, suppressed nickel sulphate-induced contact dermatitis.
This report reviews individual-related variables, environment-related variables and instrument-related variables, with a focus on the Evaporimeter EP1 (ServoMed). Start-up and use is described, and guidelines for good laboratory practice given.
To obtain data on the function of the epidermal barrier in patients with atopic dermatitis (AD) the transepidermal water loss (TEWL) was studied. Measurements were made on three body locations in two clinically well defined groups of patients with AD and in a control group. The TEWL was found to be increased both in dry non-eczematous skin and in clinically normal skin in patients with AD. The TEWL was highest in patients with dry skin. The result of the study may indicate a primary defect in the epidermal barrier: the stratum corneum.
In order to further clarify the role of intercellular lipids in the water-retention properties of the stratum corneum, forearm skin of six healthy male volunteers was treated with 5% sodium dodecyl sulfate (SDS) for 1, 10, and 30 min. All treatment periods induced chapping and scaling of the stratum corneum without any inflammatory reaction, accompanied by a significant decrease in its water-retention function. Electron-microscopic analysis of SDS-treated stratum corneum revealed selective depletion of the lipids from the intercellular spaces, accompanied by marked disruption of multiple lamellae structures. Lipid analysis also showed a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol ester, free fatty acid, and sphingolipids. To evaluate the recovery potential for intercellular lipids, lipids which were separated as sebaceous-rich lipids (SLs) and stratum corneum lipids (SCLs) were applied daily on SDS-treated forearm skin. Two daily applications of the SCLs which were emulsified at 10% concentration in W/O (water in oil) cream caused a significant increase in conductance, accompanied by a definite improvement in the level of scaling over no application or W/O emulsion base only, whereas SLs in the W/O emulsion base led to no significant recovery in either conductance value or scaling. When two daily topical applications of four chromatographically separated lipid fractions (cholesterol ester, free fatty acid, cholesterol, and sphingolipid) from the SCL were carried out at 1% concentration in the same system, the cholesterol ester and sphingolipid fractions were found to induce a significant increase in the conductance value over no application.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium dodecyl sulfate (SDS) has been used to induce a dry scaly skin condition in human subjects. Measurements of stratum (s.) corneum hydration, scaliness, and lipid composition reveal in vivo surfactant perturbations on desquamation. Subjects (n = 10) were briefly treated daily with a 4% aqueous solution of SDS on one lower leg over a period of 2 weeks. The other control leg received no treatments. At the end of the treatment period, both lower legs were evaluated for hydration using an electrical impedance technique and examined by an independent dermatologist using a visually based grading scale for surface roughness and scaliness. Shave biopsies were then excised from each lower leg for analysis of s. corneum lipids. Treatment resulted in decreased s. corneum hydration and increased surface scale/roughness. These physical changes were accompanied by significant changes in s. corneum lipid composition. While surfactant treatments did not alter the total quantity of lipids per gram s. corneum protein, significant changes in specific lipid classes were observed. The free cholesterol to cholesterol ester ratio increased while the quantity of total sterols remained constant. The distribution of certain ceramide species were altered while the quantity of total ceramides remained constant. Free fatty acids were resolved into 2 distinct bands, only one of which diminished upon treatment. These results are interpreted in terms of a model for surfactant-induced perturbation of keratinization which leads to abnormal s. corneum lipids and altered desquamation.
Erythrocyte selenium-dependent glutathione peroxidase activity was measured in psoriatic Danes, before and after their four-week balneological therapy at the Ein-Bokek International Psoriasis Treatment Center, on the Dead-Sea shore in Israel. The drinking water in Ein-Bokek was found to be rich in selenium, a trace element with anticarcinogenic properties and of great importance in human nutrition and health. The most reliable biological parameter for increase in selenium bioavailability is the erythrocytes' glutathione-peroxidase activity. As psoriasis is a proliferative skin disease, the activity of this enzyme was assayed in 35 psoriatic Danes and in 25 long-term local hotel workers, as well as in 34 volunteers drinking low-selenium water. The glutathione peroxidase activity in the psoriatic patients increased significantly during their four-week stay in Ein-Bokek. Erythrocyte glutathione peroxidase activity in the hotel workers was 50% higher than that in the healthy volunteers consuming low-selenium water. A possible role of selenium in psoriasis is suggested.
— Using an electrolytic hygrometer, the Transepidermal Water Loss (T.W.L.) from the skin was measured in normal individuals and in patients with dermatitis (eczema). It was found that there was a close correlation between T.W.L. and the state of activity of the dermatitis; and that there was a gradual reduction in abnormally raised T.W.L. in parallel with the return to normal of the skin response (dermatitis). Sweating did not contribute to the increased insensible water loss in dermatitis under the fixed limits of ambient temperature and humidity of this investigation.
Accruing evidence indicates that the levels of extracellular Mg2+ and Ca2+ can have a distinct impact on the adhesive and migratory activities of many cell types. The physiological relevance of these observations, however, has remained largely unexplored. In the present study, wound fluids collected throughout the early stages of cutaneous wound repair were examined for possible Mg2+ and Ca2+ fluctuations. Early in the process, when cell migration into the wound site is initiated, Mg2+ is elevated and Ca2+ is reduced (Mg2+:Ca2+ = 1). As wound healing progresses, wound fluid concentrations of Mg2+ and Ca2+ begin to return to normal plasma levels (Mg2+:Ca2+ = 0.4). When macrophages, keratinocytes, fibroblasts, and endothelial cells were exposed to dialyzed wound fluid, the migration stimulated by undialyzed wound fluid was lost. Addition back to dialyzed wound fluid of 24 h, postinjury concentrations of Mg2+ and Ca2+ restored all migratory stimulus. This observed migration is approximately twofold greater than when normal plasma Mg2+ and Ca2+ concentrations are present. Changes in the levels of Mg2+ and Ca2+ in wound fluid occur during the same period that inflammatory cells, keratinocytes, fibroblasts, and neovasculature have been shown to migrate during wound healing in vivo. Together, these data suggest that the impact of these changes on integrins and E-cadherin may play a direct role in the activation and maintenance of the migratory phenotypes of the cells involved in the wound healing process.
Two commercially available electrical instruments which evaluate the hydration state of the skin surface were compared in in vitro and in vivo experiments. The skin surface hygrometer (Skicon-200) employs high-frequency conductance, whereas the corneometer (CM 420, CM 820) uses electrical capacitance to determine the level of hydration. In a simulation model of in vivo stratum corneum (SC), the high frequency conductance device showed a much closer correlation with the hydration state of the surface SC (r = 0.99) than the capacitance device (r = 0.79), suggesting that the former can accurately assess the hydration dynamics of SC, particularly that due to the accumulation of easily releasable secondary bound water and free water. Both devices were insensitive to changes of hydration taking place in deeper viable skin tissues, e.g. the accumulated tissue fluids in suction blisters. Although the capacitance device correlated poorly with the hydration dynamics in normal SC, its sensitivity to changes occurring in extremely dry skin, such as scaly psoriatic lesions, suggests its measurements characteristics at an extremely low state of hydration, consisting of mostly bound water, such as noted in pathologic SC.
In order to obtain objective data on skin functions in subjects with atopic dermatitis (AD), according to the different phases of the disease, we evaluated the skin of children with AD instrumentally and compared it to that of healthy subjects of the same age group. One hundred patients, aged 3 to 12, and 21 healthy children were studied by means of measurements of pH, capacitance and transepidermal water loss (TEWL) at 8 different skin sites. At the moment of the investigation 55 children out of 100 presented skin lesions on at least one of the assessed skin areas, whereas 45 had been free from eczema for at least 1 month. Considering all skin sites together, significant differences were found between mean values of pH, capacitance and TEWL of eczematous skin, both in respect to those referring to apparently healthy skin in the same patients and in respect to the skin of control subjects. Moreover, TEWL, pH and capacitance values referring to uninvolved skin of AD patients significantly differed from those of healthy subjects. Finally, when values referring to patients with skin lesions and to patients without lesions were separately considered, significant differences concerning the parameters of uninvolved skin were observed. These data show that, in subjects with AD, skin functions undergo fluctuations according to the phase of the disease and support the hypothesis that the presence of active eczema determines an impairment of the barrier of uninvolved skin, even at sites far from active lesions.
The effect of five selected minerals abundant in the Dead-sea brine was studied on proliferation of fibroblasts grown from psoriatic and healthy skin biopsy specimens in cell culture. The reason for carrying out this study was looking for the mechanism of the antiproliferative effect of selective Dead-sea minerals in improving the psoriatic condition. Psoriatic skin shave biopsy specimens (both from involved and uninvolved areas of the body) as well as healthy skin (obtained from amputated limbs) were incubated in tissue culture, and their outgrowing fibroblasts were used for this study. The number of cells and their cyclic AMP content were used as parameters for cell division and for proving the selective involvement of magnesium salts in the antiproliferative effect. It is shown that the inhibitory effects of magnesium bromide and magnesium chloride on cell growth were significantly stronger than those of their corresponding potassium salts or of sodium chloride. These results were obtained with both psoriatic and healthy skin fibroblasts, indicating that the inhibitory effect of the selected Dead-sea minerals is present in healthy and psoriatic skin cells.
This report reviews individual-related variables (age, sex, race, anatomical site, skin surface properties), intra- and interindividual variation (temporal, physical and mental activity, orthostatic effect, menstrual cycle/menopause), environment-related variables (light conditions, temperature) and various instrument-related variables that influence skin colour. CIE colorimetry (Minolta Chroma Meter) and spectrophotometric measurement (Derma Spectrometer) are considered. The guidelines give recommendations for measuring conditions and procedures.
The hallmarks of dry skin (xerosis) are scaliness and loss of elasticity. Decreased hydration and a disturbed lipid content of the stratum corneum are also well-known features. The frequency of dry skin increases with ageing. The aim of this study was to examine if these known features of dry skin are related to changes in epidermal proliferation and differentiation. In addition, age-related changes in normal and in dry skin were examined: 62 volunteers were divided by clinical grading and biophysical measurements into groups with young/normal, young/dry, aged/normal and aged/dry skin. Biopsy samples from the lower legs (most severe dryness) were examined by two-dimensional gel electrophoresis and by immunohistochemistry for epidermal proliferation, epidermal keratins and cornified envelope proteins. There was a slight increase in proliferation in both groups with dry skin compared with normal skin of the corresponding age. In aged/normal compared with young/normal skin there was a significant decrease in proliferation. However, epidermal proliferation was the same in aged/dry skin as in young/normal skin. For epidermal differentiation, an age-independent decrease of keratins K1 and K10 and an associated increase in the basal keratins K5 and K14 was detected in dry skin. There was also an age-independent premature expression of the cornified envelope protein involucrin. In contrast, loricrin expression was not influenced by dry skin conditions. In summary, epidermal proliferation was significantly decreased in aged/normal compared with young/normal skin. Dry skin showed significant changes in the epidermal expression of basal and differentiation-related keratins, and a premature expression of involucrin irrespective of age.
In irritancy studies, measurement of transepidermal water loss (TEWL) is a widely used technique to assess barrier function. Using inappropriate statistical methods, however, leads to loss of information and misinterpretation of results. In this paper, we discuss some problems and pitfalls when using a suitable statistical technique for most designs in bioengineering studies, analysis of variance (ANOVA): multiple comparisons, choice of sample size and violation of statistical assumptions. For clarification of these points, a practical example will be given. Using the proposed adequate statistical methods correctly will, although accompanied by increased complexity, increase the efficiency of bioengineering studies.
The effects of four different magnesium salts on the cutaneous barrier recovery rate after barrier disruption were evaluated. We spread an aqueous solution of each salt on the flank skin of hairless mice, occluded the area with a plastic membrane for 20 min, and then left the skin surface to dry. All of the magnesium salts, except magnesium bis(dihydrogen phosphate), accelerated barrier repair. We next estimated the effects of magnesium chloride aqueous solutions which contained calcium chloride at different molar ratios. When the calcium to magnesium ratio was lower than 1, the mixture accelerated barrier repair. The application of an aqueous solution of 10 mM magnesium chloride and 10 mM calcium chloride was found to hasten the barrier recovery more effectively than a solution of 10 mM magnesium chloride. These results suggest that the effects of these metal ions are different depending on the counter ion and/or the method of application.
Although it has been well established that the dry skin often seen in patients with atopic dermatitis shows a deranged barrier function, there is no unanimity of opinion as to whether the barrier in normal-appearing skin of patients with the disease is deranged or not. Hence, it remains unclear whether individuals with atopic dermatitis constitution have an intrinsic derangement of skin barrier function or not. To settle this problem, in the present study we examined transepidermal water loss and stratum corneum water content in normal appearing skin of the upper back of 16 patients with completely healed atopic dermatitis who had been free from skin symptoms for 5 years or more, 30 patients with active atopic dermatitis, and 39 healthy subjects. The transepidermal water loss values and the stratum corneum water content values in normal-appearing skin of the completely healed patients were not different from the values in normal controls. These findings indicate that skin barrier function is not disturbed in patients with completely healed atopic dermatitis.
Irritant substances have been shown to induce elemental changes in human and animal epidermal cells in situ. However, skin biopsies are a complicated experimental system and artefacts can be introduced by the anaesthesia necessary to take the biopsy. We therefore attempted to set up an experimental system for X-ray microanalysis (XRMA) consisting of cultured human keratinocytes. A number of methodological aspects were studied: different cell types, washing methods and different culture periods for the keratinocytes. It was also investigated whether the keratinocytes responded to exposure to sodium lauryl sulphate (SLS) with changes in their elemental composition. The concentrations of biologically important elements such as Na, Mg, P and K were different in HaCaT cells (a spontaneously immortalized non-tumorigenic cell line derived from adult human keratinocytes) compared to natural human epidermal keratinocytes. The washing procedure and time of culture influenced the intracellular elemental content, and rinsing with distilled water was preferred for further experiments. Changes in the elemental content in the HaCaT cells compatible with a pattern of cell injury followed by repair by cell proliferation were seen after treatment with 3.33 microM and 33 microM SLS. We conclude that XRMA is a useful tool for the study of functional changes in cultured keratinocytes, even though the preparation methods have to be strictly controlled. The method can conceivably be used for predicting effects of different chemicals on human skin.
The combination of seawater baths and solar radiation at the Dead Sea is known as an effective treatment for patients with psoriasis and atopic dermatitis. Dead Sea water is particularly rich in magnesium ions. In this study we wished to determine the effects of magnesium ions on the capacity of human epidermal Langerhans cells to stimulate the proliferation of alloreactive T cells. Twelve subjects were exposed on four subsequent days on the volar aspects of their forearms to 5% MgCl2, 5% NaCl, ultraviolet B (1 minimal erythemal dose), MgCl2 + ultraviolet B, and NaCl + ultraviolet B. Epidermal sheets were prepared from punch biopsies and were stained for ATPase and HLA-DR. Compared with untreated skin, the number of ATPase+/HLA-DR+ Langerhans cells was significantly reduced after treatment with MgCl2 (p = 0.0063) or ultraviolet B (p = 0.0005), but not after NaCl (p = 0.7744). We next questioned whether this reduced expression of ATPase and HLA-DR on Langerhans cells bears a functional relevance. Six subjects were treated on four subsequent days with 5% MgCl2, ultraviolet B (1 minimal erythemal dose), and MgCl2 + ultraviolet B. Epidermal cell suspensions from treated and untreated skin were assessed for their antigen-presenting capacity in a mixed epidermal lymphocyte reaction with allogeneic naive resting T cells as responder cells. Treatment with MgCl2, similarly to ultraviolet B, significantly reduced the capacity of epidermal cells to activate allogeneic T cells (p = 0.0356). Magnesium ions also suppressed Langerhans cells function when added to epidermal cell suspensions in vitro. The reduced antigen-presenting capacity of Langerhans cells after treatment with MgCl2 was associated with a reduced expression by Langerhans cells of HLA-DR and costimulatory B7 molecules, and with a suppression of the constitutive tumor necrosis factor-alpha production by epidermal cells in vitro. These findings demonstrate that magnesium ions specifically inhibit the antigen-presenting capacity of Langerhans cells and may thus contribute to the efficacy of Dead Sea water in the treatment of inflammatory skin diseases.
- Werner Y