PUBLICATION BOOKLET 3RD EDITION

Transcription

1 PUBLICATION BOOKLET 3RD EDITION

2

3 PUBLICATION BOOKLET 3RD EDITION

4 ACO HUD NORDIC AB is the leading skin care company in the Nordics. Covering the range from topical pharmaceuticals to exclusive skin care products, our product portfolio offers both width and depth. With research and laboratory in-house, we develop safe products with modern formulations for the Nordic consumer. Through our knowledge and evidence-based approach we add value within the skin care sector. With transparency as a key word for all our work, we frequently present and publish the results of our research. This booklet contains scientific publications on ACO s reserach within the field of dermatology. Clinical studies on our medicinal products as well as review articles are presented. 4

5 CONTENTS Emollients in general Prevention or promotion of dryness and eczema by moisturizers? Lodén M. Exp Rev Dermatol 2008; 3(6): The clinical benefit of moisturizers. Lodén M. JEADV 2005; 19: SUN PROTECTION Accumulation of sunscreen in human skin after daily applications: a study of sunscreens with different ultraviolet radiation filters. Bodekaer M, Akerstrom U, Wulf HC. Photodermatol Photoimmunol Photomed 2012; 28: Sunscreen use: controversies, challenges and regulatory aspects. Lodén M, Beitner H, Gonzalez H, Edström DW, Akerström U, Austad J, Buraczewska-Norin I, Matsson M, Wulf HC. Br J Dermatol 2011; 165(2): QUALITY OF LIFE Increasing quality of life by improving the quality of skin in patients with atopic dermatitis. Halvarsson K, Lodén M. Int J Cosm Sci 2007; 29: CANODERM The effect of a corticosteroid cream and a barrier-strengthening moisturizer in hand eczema. A double-blind, randomized, prospective, parallel group clinical trial. Lodén M, Wirén K, Smerud K, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding M. JEADV 2012; 26(5): Treatment with a barrier-strengthening moisturizer prevents relapse of hand-eczema. An open, randomized, prospective, parallel group study. Lodén M, Wirén K, Smerud K, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding M. Acta Derm Venerol 2010: 90: Cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy vs. no treatment after an initial steroid course in patients with atopic dermatitis in Sweden with model applications for Denmark, Norway and Finland. Hjalte F, Asseburg C, Tennvall GR. JEADV 2010; 24(4):

6 Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis. A prospective and randomized controlled clinical trial. Wirén K, Nohlgård C, Nyberg F, L Holm L, Svensson M, Johannesson A, Wallberg P, B Berne B, Edlund F, Lodén M. JEADV 2009; 23: Moisturizers change the mrna expression of enzymes synthesizing skin barrier lipids. Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Arch Dermatol Res 2009; 301: Changes in skin barrier function by long-term treatment with moisturizers. Buraczewska I, Berne B, Lindberg M, Törmä H, Lodén M. Br J Dermatol 2007; 156: Long-term treatment with moisturizers affects the mrna levels of genes involved in keratinocyte differentiation and desquamation. Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Br J Dermatol 2007; 156: Treatment of surfactant-damaged skin in humans with creams of different ph. Buraczewska I, Lodén M. Pharmacology 2005; 73: 1-7. Exogen Dermatol 2005; 73: Effects of pre-treatment an emollient containing urea on nickel allergic skin reactions. Kuzmina N, Nyrén M, Lodén M, Edlund F, Emtestam L. Acta Derm Venereol 2005; 85: The influence of urea treatment on skin susceptibility to surfactant-induced irritation: A placebo-controlled and randomized study. Lodén M, Bárány E, Mandahl P, Wessman C. Exog Dermatol 2004; 3: Nickel susceptibility and skin barrier function to water after treatment with a urea-containing moisturizer. Lodén M, Kuzima N, Nyrén M, Edlund F, Emtestam L. Exog Dermatol 2004; 3: Differences among moisturizers in affecting skin susceptibility to hexyl nicotinate, measured as time to increase skin blood flow. Duval C, Lindberg M, Boman A, Johansson S, Edlund F, Lodén M. Skin Res Technol 2003; 9: Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis. Lodén M, Andersson AC, Andersson C, Frödin T, Öman H, Lindberg M. Skin Res Technol 2001; 7: Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm ). Lodén M, Andersson A-C, Lindberg M. Br J Dermatol 1999; 140: The effect of two urea-containing creams on dry, eczematous skin in atopic patients. I. Expert, patient and instrumental evaluation. Andersson A-C, Lindberg M, Lodén M. J Dermatol Treat 1999; 10:

7 The effect of two urea-containing creams on dry, eczematous skin in atopic patients. II. Adverse effects. Lodén M, Andersson A-C, Lindberg M. J Dermatol Treat 1999; 10: Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream. Lodén M. Contact Dermatitis 1997; 36: MINIDERM A double-blind study comparing the effect of glycerine and urea on dry, eczematous skin in atopic patients. M Lodén, A-C Andersson, A Anderson, I-M Bergrant, T Frödin, H Öhman, M-H Sandström, T Särnhult, E Voog, B Stenberg, E Pawlik, A Preisler-Häggqvist, Å Svensson & M Lindberg. Acta Dermato-Venerologica 2002; 82: The influence of a cream containing 20 % glycerine and its vehicle on skin barrier properties. Lodén M, Wessman C. Int J Cosm Sci 2001; 23: LIST OF SCIENTIFIC PUBLICATIONS

8 Emollients in general Prevention or promotion of dryness and eczema by moisturizers? Lodén M. Expert Review of Dermatology 2008; 3(6): The use of moisturizers is almost instinctive and is also routinely recommended to reduce the likelihood of developing dryness and eczema. However, recent findings demonstrate that treatment with creams may increase the risks for eczema. Symptoms of dryness may appear in normal skin and the skin susceptibility to outside stressors may increase. Moisturizing creams contain a great variety of ingredients, some of which are found in the stratum corneum. However, knowledge regarding the mechanisms of the impact of different ingredients on the skin is still lacking and, currently, it is a matter of trial and error to find the most suitable moisturizer for an individual. The cosmetic properties and the simplicity to use the products are important parameters for adherence, but even more important are the effects on the skin barrier function. A defect in skin barrier function has been suggested as the major cause for atopic eczema. Increased rate of transepidermal water loss (TEWL) induces signals that stimulate normalization of the skin barrier function, but increased TEWL can also have pathological effects, which results in cutaneous abnormalities. Therefore, we propose TEWL to be a surrogate parameter for the changed risks for development of eczema by moisturizer treatment. 8

9 The clinical benefit of moisturizers Lodén M. Journal of the European Academy of Dermatology and Venereology 2005; 19: Moisturizing creams marketed to consumers often contain trendy ingredients and are accompanied by exciting names and attractive claims. Moisturizers are also an important part of the dermatologist s armamentarium to treat dry skin conditions and maintain healthy skin. The products can be regarded as cosmetics, but may also be regulated as medicinal products if they are marketed against dry skin diseases, such as atopic dermatitis and ichtyosis. When moisturizers are used on the so-called dry skin, many distinct disorders that manifest themselves with the generally recognized symptoms of dryness are treated. Dryness is not a single entity, but is characterized by differences in chemistry and morphology in the epidermis depending on the internal and external stressors of the skin. Patients and the society expect dermatologists and pharmacists to be able to recommend treatment for various skin conditions upon evidence-based medicine. Upon completing this paper, the reader should be aware of different types of moisturizers and their major constituents. Furthermore, s/he will know more about the relief of dryness symptoms and the functional changes of the skin induced by moisturizers. 9

10 SUN PROTECTION ACCUMULATION OF SUNSCREEN IN HUMAN SKIN AFTER DAILY APPLICATIONS: A STUDY OF SUNSCREENS WITH DIFFERENT ULTRAVIOLET RADIATION FILTERS Bodekaer M, Akerstrom U, Wulf HC. Photodermatology, Photoimmunology & Photomedicine 2012; 28: Sunscreen applied to the skin provides a considerable sun protection factor (SPF) even after 8 h. Sunscreen use for consecutive days may therefore result in an accumulation of the product. This study investigated the consequences of accumulation for SPF. Two sunscreens, one containing organic and one containing particle ultraviolet radiation (UVR) filters (SPF 30) (2 mg/cm 2 ), were used. Areas on the back of 22 volunteers were applied with sunscreen on 5 consecutive days, once daily (12 volunteers) and three times daily (10 volunteers), and phototested. The SPF was determined on Days 1, 3 and 5. One daily application of sunscreen did not result in an accumulation in the skin that significantly affected the SPF. However, three daily applications provided a significantly higher SPF for both the organic (mean SPF 1.56) and particle (mean SPF 2.45) sunscreen at Day 5 compared to Day 1 (p = 0,023 for both sunscreens). Sunscreens accumulate in the skin when applied in the recommended amounts three times daily. In conjunction with other sun protection strategies, sunscreen application on consecutive days prior to UVR exposure can result in a basic skin protection, which may help to prevent severe sunburns on sun holidays. 10

11 SUNSCREEN USE: CONTROVERSIES, CHALLENGES AND REGULATORY ASPECTS Lodén M, Beitner H, Gonzalez H, Edström DW, Akerström U, Austad J, Buraczewska-Norin I, Matsson M, Wulf HC. British Journal of Dermatology 2011; 165(2): Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight. 11

12 QUALITY OF LIFE Increasing quality of life by improving the quality of skin in patients with atopic dermatitis Halvarsson K, Lodén M. International Journal of Cosmetic Science 2007; 29: Atopic dermatitis is a chronic relapsing inflammatory skin disease which usually starts during the first years of life. In patients with the disease, the quality of skin is severely affected, and this is closely linked to a reduced quality of life. An increasing prevalence of the disease has also been observed during recent years, which has been attributed to potential provocation factors in the environment. The environmental influence of the disease is complex, but the role of stratum corneum as a biosensor regulating the response to a variety of insults has been suggested as one crucial factor. Therefore, our daily hygiene and treatment of dryness are necessary measures to improve the quality of life and possibly reduce the frequency of the disease. Soaps as well as moisturizers show important differences in their impact on barrier function. 12

13 Canoderm THE EFFECT OF A CORTICOSTEROID CREAM AND A BARRIER- STRENGTHENING MOISTURIZER IN HAND ECZEMA. A DOUBLE-BLIND, RANDOMIZED, PROSPECTIVE, PARALLEL GROUP CLINICAL TRIAL Lodén M, Wirén K, Smerud KT, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding B. Journal of the European Dermatology and Venerology 2012; 26(5): Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment. The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema. The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1 %) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient s skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale. Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion. Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion. 13

14 Canoderm TREATMENT WITH A BARRIER-STRENGTHENING MOISTURIZER PREVENTS RELAPSE OF HAND-ECZEMA. AN OPEN, RANDOMIZED, PROSPECTIVE, PARALLEL GROUP STUDY Lodén M, Wirén K, Smerud K, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding B. Acta Dermatology and Venerology 2010; 90(6): Hand eczema influences the quality of life. Management strategies include the use of moisturizers. In the present study the time to relapse of eczema during treatment with a barrier-strengthening moisturizer (5 % urea) was compared with no treatment (no medical or non-medicated preparations) in 53 randomized patients with successfully treated hand eczema. The median time to relapse was 20 days in the moisturizer group compared with 2 days in the no treatment group (p = 0.04). Eczema relapsed in 90 % of the patients within 26 weeks. No difference in severity was noted between the groups at relapse. Dermatology Life Quality Index (DLQI) increased significantly in both groups; from 4.7 to 7.1 in the moisturizer group and from 4.1 to 7.8 in the no treatment group (p < 0.01) at the time of relapse. Hence, the application of moisturizers seems to prolong the disease-free interval in patients with controlled hand eczema. Whether the data is applicable to moisturizers without barrier-strengthening properties remains to be elucidated. 14

15 Cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy vs. no treatment after an initial steroid course in patients with atopic dermatitis in Sweden with model applications for Denmark, Norway and Finland Hjalte F, Asseburg C, Tennvall GR. Journal of the European Dermatology and Venerology 2010; 24(4): Atopic dermatitis (AD) affects health and quality of life and it has great impact on both health-care costs and costs to the society. The objective of this study was to develop a model to analyse the cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy compared with no treatment after initial treatment with betamethasone valerate in adult patients with AD in Sweden. A further aim was to apply a similar health-economic analysis for Denmark, Norway and Finland. A Markov simulation model was developed including data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate AD treated with either a moisturizing cream or no treatment, (ii) resource utilization and quality of life data, and (iii) unit prices from official price lists. A societal perspective was used and the analysis was performed according to treatment practice in Sweden. The model simulation was also applied for Denmark, Norway and Finland with inclusion of country-specific unit costs. Sensitivity analyses were performed to test the robustness of the results. The results from the present analyses of treatment for patients with moderate AD indicate that maintenance treatment with a moisturizing cream during eczema-free periods could be cost-effective in a societal perspective. Similar results were obtained for Sweden, Denmark, Norway and Finland. According to the analysis, treatment with a moisturizing cream was found to be a cost-effective option compared with no treatment in eczemafree periods in adult patients with AD in the four Nordic countries. 15

16 Canoderm Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial Wirén K, Nohlgård C, Nyberg F, Holm L, Svensson M, Johannesson A, Wallberg P, Berne B, Edlund F, Lodén M. Journal of the European Academy of Dermatology and Venereology 2009; 23(11): Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction. The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function. Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator. Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period. Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment. 16

17 Moisturizers change the mrna expression of enzymes synthesizing skin barrier lipids Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Archives of Dermatological Research 2009; 301(8): In a previous study, 7-week treatment of normal human skin with two test moisturizers, Complex cream and Hydrocarbon cream, was shown to affect mrna expression of certain genes involved in keratinocyte differentiation. Moreover, the treatment altered transepidermal water loss (TEWL) in opposite directions. In the present study, the mrna expression of genes important for formation of barrier lipids, i.e., cholesterol, free fatty acids and ceramides, was examined. Treatment with Hydrocarbon cream, which increased TEWL, also elevated the gene expression of GBA, SPTLC2, SMPD1, ALOX12B, ALOXE3, and HMGCS1. In addition, the expression of PPARG was decreased. On the other hand, Complex cream, which decreased TEWL, induced only the expression of PPARG, although not confirmed at the protein level. Furthermore, in the untreated skin, a correlation between the mrna expression of PPARG and ACACB, and TEWL was found, suggesting that these genes are important for the skin barrier homeostasis. The observed changes further demonstrate that long-term treatment with certain moisturizers may induce dysfunctional skin barrier, and as a consequence several signaling pathways are altered. 17

18 Canoderm Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial Buraczewska I, Berne B, Lindberg M, Törmå H, Lodén M. British Journal of Dermatology 2007; 156: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers are still scarce. The aim of this study was to investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. Volunteers (n=78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. 18

19 After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulphate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated for 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be non-irritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level. 19

20 Canoderm Long-term treatment with moisturizers affects the mrna levels of genes involved in keratinocyte differentiation and desquamation Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Archives of Dermatological Research 2009; 301: In a recent study, we showed that long-term treatment with two different moisturizers affected TEWL in opposite directions. Therefore, we decided to examine the effect of these moisturizers on the cellular and molecular level. In a randomized controlled study on 20 volunteers, epidermal mrna expression of genes essential for keratinocyte differentiation and desquamation after a 7-week treatment with two moisturizers was analyzed. Treatment with one test moisturizer increased gene expression of involucrin, transglutaminase 1, kallikrein 5, and kallikrein 7, while the other moisturizer affected only expression of cyclin-dependent kinase inhibitor 1A. Thus, moisturizers are able to modify the skin barrier function and change the mrna expression of certain epidermal genes. Since the type of influence depends on the composition of the moisturizer, these should be tailored in accordance with the requirement of the barrier of each individual patient, which merits further investigations. 20

21 TREATMENT OF SURFACTANT-DAMAGED SKIN IN HUMANS WITH CREAMS OF DIFFERENT PH Buraczewska I, Lodén M. Pharmacology 2005; 73(1): 1-7. Skin surface has an acidic ph, whereas the body s internal environment maintains a near-neutral ph. The physiological role of the acidic mantle and the function of the ph gradient throughout the stratum corneum remain unexplained. The ph gradient has been suggested to activate enzymes responsible for the maintenance of the skin barrier function and to facilitate the desquamation process in the stratum corneum. The aim of the study was to investigate the influence of ph of a moisturizing cream on barrier recovery in surfactant-damaged human skin. Volunteers had their skin damaged with sodium lauryl sulphate and treated those areas with the cream, adjusted to either ph 4.0 or 7.5. The study did not prove the superiority of a cream of ph 4.0 to a cream of ph 7.5 regarding promotion of skin barrier recovery, since no significant differences (p > 0.05) were found in transepidermal water loss, blood flow and skin capacitance between the treated areas. 21

22 Canoderm Effects of pretreatment with a urea-containing emollient on nickel allergic skin reactions Kuzmina N, Nyrén M, Lodén M, Edlund F, Emtestam L. Acta Dermato-Venereologica 2005; 85: The aim of this study was to evaluate the effect of a moisturizer containing urea on nickel-sensitized volunteers patients and five controls (non-sensitized volunteers) applied such a moisturizer on the volar side of one forearm twice daily for 20 days, while the other forearm served as the control. After treatment with the moisturizer, patch tests with 0%, 0,5% and 2% NiSO 4 in petrolatum were applied in a randomized manner on each arm. After 72 h, the skin reactions were blindly evaluated by clinical scoring and by measuring transepidermal water loss and electrical impedance. After treatment, the baseline transepidermal water loss values were lower and the baseline magnitude impedance index values were higher on the pretreated forearm. According to clinical scoring and measurements with the two physical measurement techniques, the degree of the patch test reactions was equal. All control subjects had negative nickel tests. We concluded that the skin reactivity to nickel in nickel-sensitized patients is not significantly affected by use of the urea-containing moisturizer. 22

23 THE INFLUENCE OF UREA TREATMENT ON SKIN SUSCEPTIBILITY TO SURFACTANT-INDUCED IRRITATION: A PLACEBO-CONTROLLED AND RANDOMIZED STUDY Lodén M, Bárány E, Mandahl P, Wessman C. Exogenous Dermatology 2004; 3: 1 6. Certain ingredients in moisturizing creams may influence the skin susceptibility to irritants. One agent of particular interest is the well-known humectant urea. The present placebo-controlled study on 28 subjects was designed to evaluate the effects of urea treatment on three types of sodium lauryl sulphate (SLS) exposures: (1) repeated exposure to SLS for 15 days with concurrent cream treatment, (2) the skin susceptibility to SLS following prophylactic treatment with urea and (3) SLS exposure after recovery of the surfactant-damaged skin by urea treatment. Parameters measured were transepidermal water loss (TEWL) and skin blood flow. Repeated exposure to SLS induced a slight but significant barrier damage, measured as TEWL, and the difference between the treatments was almost significant (p = 0.06). Treatment of normal skin reduced TEWL in the urea-treated area, and the irritant reaction to SLS was significantly decreased. Treatment of surfactant-damaged skin promoted barrier recovery, and the second exposure to SLS induced a less pronounced reaction in the urea-treated area compared to the placebo-treated site. In conclusion, urea promotes barrier recovery in SLS-damaged skin and makes both normal and irritated skin less susceptible to irritation. The findings may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli. 23

24 Canoderm NICKEL SUSCEPTIBILITY AND SKIN BARRIER FUNCTION TO WATER AFTER TREATMENT WITH A UREA-CONTAINING MOISTURIZER Lodén M, Kuzmina N, Nyrén M, Edlund F, Emtestam L. Exogenous Dermatology 2004; 3: Patients with eczema and other dry skin conditions use moisturizers also when the skin appears healthy. However, moisturizers have been found to change skin barrier function, and it appears that certain combinations of ingredients increase the skin susceptibility to external agents. In the present randomized and singleblind study, the influence of a urea-containing cream on nickel susceptibility in 35 patients with known allergy to nickel was evaluated. Treatment of the volar forearm twice daily for 20 days with the urea cream reduced transepidermal water loss (TEWL). However, the susceptibility to nickel sulfate was not changed by the cream treatment. Clinical scoring of the skin reaction did not show any difference between the untreated and the cream-treated area. Furthermore, the increase in TEWL did not differ between the areas. The absence in correlation between TEWL and skin susceptibility to nickel suggests different penetration pathways through the skin of water and nickel. Measurement of the skin permeability to other substances than water is pertinent to the understanding of the influence of moisturizers on the skin permeability and, ultimately, to their therapeutic efficacy in the prevention of contact eczema due to exposure to harmful exogenous substances. 24

25 Differences among moisturizers in affecting skin susceptibility to hexyl nicotinate, measured as time to increase skin blood flow Duval C, Lindberg M, Boman A, Johnsson S, Edlund F, Lodén M. Skin Research and Technology 2003; 9: A wide range of branded and generic moisturizers is frequently used for the prevention and treatment of dry skin. The influence of the moisturizers on the skin permeability is pertinent to the understanding of their therapeutic efficacy. The aim of the present study was to compare the effect of two moisturizers on the skin permeability barrier, assessed as skin reactivity to a vasodilating substance. The study was parallel, randomized and double blind on 53 healthy volunteers. One of the creams contained 5% urea, whereas the other contained no humectant but had a high lipid content. The participants were instructed to apply the cream twice daily for three weeks on the volar aspect of one of their forearms. The skin was then exposed to hexyl nicotinate, which induces vasodilatation. The time-course and magnitude of the microvascular changes in the two skin areas were monitored with a non-invasive optical technique (laser Doppler flowmetry) with two measuring probes. The lag-time between application and initial response was significantly longer for the urea-treated site compared with the other cream. Furthermore, the time for maximum response was shorter for the lipid-rich cream than for its placebo. The study shows differences in action between moisturizers, which may influence the skin susceptibility to other irritants and allergens in the environment. 25

26 Canoderm INSTRUMENTAL AND DERMATOLOGIST EVALUATION OF THE EFFECT OF GLYCERINE AND UREA ON DRY SKIN IN ATOPIC DERMATITIS. Lodén M, Andersson AC, Andersson C, Frödin T, Oman H, Lindberg M. Skin Research and Technology 2001; 7(4): Moisturising creams are useful treatment adjuncts in inflammatory dermatoses and have beneficial effects in the treatment of dry, scaly skin. The effects on dryness and skin permeability of a new moisturising cream with 20 % glycerine was compared with its placebo and with a medicinally authorised cream with 4 % urea (combined with 4 % sodium chloride) in the treatmentof dry skin. Patients (n=109) with atopic dermatitis were treated for 30 days with a moisturiser in a randomised, parallel and double-blind fashion. Transepidermal water loss (TEWL) and skin capacitance were assessed instrumentally, and changes in the dryness of the skin were assessed by the dermatologist. No difference in TEWL was found between glycerine treatment and its placebo, whereas a lower value was found in the urea-treated area compared to the glycerine-treated area. No difference in skin capacitance was found. The clinical assessment of dryness showed urea to be superior to glycerine in treating the condition. Moisturising creams are different, not only with respect to composition but also with respect to their influence on skin as a barrier to water in patients with atopic dermatitis. 26

27 Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm ) Lodén M, Andersson A-C, Lindberg M. British Journal of Dermatology 1999; 140: Patients with atopic skin show a defective barrier function both in rough and in clinically normal skin, with an increasing risk of developing contact dermatitis. Moisturizing creams are often used in the treatment of dry skin. The purpose of this study was to investigate the influence of treatment with a urea-containing moisturizer on the barrier properties of atopic skin. Fifteen patients with atopic dermatitis treated one of their forearms twice daily for 20 days with a moisturizing cream. Skin capacitance and transepidermal water loss (TEWL) were measured at the start of the study and after 10 and 20 days. On day 21 the skin was exposed to sodium lauryl sulphate (SLS) and on day 22 the irritant reaction was measured non-invasively. Skin capacitance was significantly increased by the treatment, indicating increased skin hydration. The water barrier function, as reflected by TEWL values, tended to improve (P=0.07). And the skin susceptibility to SLS was significantly reduced, as measured by TEWL and superficial skin blood flow (P<0.05). Thus, it seems that certain moisturizers could improve skin barrier function in atopics and reduce skin susceptibility to irritants. The mechanism and the clinical relevance need further investigation. 27

28 Canoderm The effect of two urea-containing creams on dry, eczematous skin in atopic patients. I. Expert, patient and instrumental evaluation Andersson A-C, Lindberg M, Lodén M. Journal of Dermatological Treatment 1999; 10: The management of atopic dermatitis includes moisturizing creams, although scientific studies of their influence on the skin are scarce. In the present randomized, double-blind study, the effects of a new moisturizing cream were compared with those of an already registered medicinal cream in the treatment of dry eczematous skin in atopic patients, using multiple methods. The new cream contained 5% urea as active substance and the established licensed cream contained 4% urea and 4% sodium chloride as active ingredients. The new cream was studied in 25 patients and the established cream was tested in 23 patients. The patients were asked to apply the cream to dry, eczematous areas at least once daily for 20 days. At inclusion in the study and after 15 and 30 days of treatment the severity of the skin was evaluated by a dermatologist, assessed by the patients and measured in terms of transepidermal water loss (TEWL) and skin capacitance. Both groups improved during the study, but no statistically significant differences between them were found. This multiparametric approach covers different aspects of skin dryness and provides the possibility of evaluating treatment effects in a cost-effective way. 28

29 THE EFFECT OF TWO UREA-CONTAINING CREAMS ON DRY, ECZEMATOUS SKIN IN ATOPIC PATIENTS. II. ADVERSE EFFECTS Lodén M, Andersson A-C, Lindberg M. Journal of Dermatological Treatment 1999; 10: The management of atopic dermatitis includes moisturizing creams to reduce the dryness. The adverse skin reactions during topical treatment with two medicinal moisturizers were monitored in a double-blind randomized study on two parallel groups of patients with dry, eczematous skin. One cream contained 4 % urea and 4 % sodium chloride as active ingredients (23 patients), and the other 5 % urea (25 patients). The patients were asked to apply the cream at least once daily for 30 days. The cream containing urea and salt induced skin sensations in about 60 % of the patients. Significantly fewer patients experienced sensations with the 5 % urea cream. Interestingly, no correlation was found between the severity of the dry skin condition and the degree of smarting. The degree of smarting did not change from day 15 to day 31. The face was reported by the patients to be most sensitive area and five patients (four in one group and one in the other) discontinued or reduced treatment of that area. 29

30 Canoderm Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream Lodén M. Contact Dermatitis 1997; 36: Moisturizers are used daily by many people to alleviate symptoms of clinically and subjectively dry skin. Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli. In the present single-blind study, a moisturizing cream was tested for its influence both on barrier recovery in surfactant-damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate (SLS). Parameters measured were transepidermal water loss (TEWL) and skin corneometer values, indicating degree of hydration. Treatment of surfactant-damaged skin with the test cream for 14days promoted barrier recovery, as observed as a decrease in TEWL. Skin corneometer values also normalized more rapidly during the treatment. In normal skin, use of the test cream significantly reduced TEWL after 14days of treatment, and irritant reactions to SLS were significantly decreased. Skin corneometer values increased after only 1 application and remained elevated after 14days. In conclusion, the accelerated rate of recovery of surfactant-damaged skin and the lower degree of SLS-induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli. 30

31 31

32 Miniderm A double-blind study comparing the effect of glycerine and urea on dry, eczematous skin in atopic patients Lodén M, Andersson A-C, Anderson A, Bergrant I-M, Frödin T, Öhman H, Sandström M-H, Särnhult T, Voog E, Stenberg B, Pawlik E, Preisler-Häggqvist A, Svensson Å, Lindberg M. Acta Dermato-Venerologica 2002; 82: Moisturizing creams have beneficial effects in the treatment of dry, scaly skin, but they may induce adverse skin reactions. In a randomized double-blind study, 197 patients with atopic dermatitis were treated with one of the following: a new moisturizing cream with 20 % glycerine, its cream base without glycerine as placebo, or a cream with 4 % urea and 4 % sodium chloride. The patients were asked to apply the cream at least once daily for 30 days. Adverse skin reactions and changes in skin dryness were assessed by the patient and a dermatologist. Adverse skin reactions such as smarting (a sharp local superficial sensation) were felt significantly less among patients using the 20 % glycerine cream compared with the urea-saline cream, because 10 % of the patients judged the smarting as severe or moderate when using glycerine cream, whereas 24 % did so using urea-saline cream (p < ). No differences were found regarding skin reactions such as stinging, itching and dryness/irritation. The study showed equal effects on dry skin as judged by the patients and the dermatologist. In conclusion, a glycerine containing cream appears to be a suitable alternative to urea/sodium chloride in the treatment of atopic dry skin. 32

33 The influence of a cream containing 20 % glycerine and its vehicle on skin barrier properties Lodén M, Wessman C. International Journal of Cosmetic Science 2001; 23: Glycerine is widely used in cosmetics as well as in pharmaceutical formulations, mainly as humectant. In vitro studies have shown glycerine to prevent crystallization of stratum corneum model lipid mixture at low room humidity. Whether this may affect the skin barrier function during repeated application of glycerine in a cream base to normal skin is not known. Therefore, the influence of a cream containing 20 % glycerine was compared with its placebo cream in a bilateral, double-blind study on 17 healthy volunteers. The effect was evaluated as influence on hydration with a corneometer and on skin barrier function. Skin barrier function was assessed as permeability to water with an evaporimeter (transepidermal water loss; TEWL) and as sensitivity to an irritating surfactant by measuring the biological response (measured as TEWL and skin blood flow). Ten days treatment of normal skin with 20 % glycerine significantly increased skin corneometer values, indicating an increased hydration. However, our study failed to show an influence of glycerine on human skin, in terms of TEWL and skin sensitivity to SLS-induced irritation. 33

34 LIST OF SCIENTIFIC PUBLICATIONS Original Scientific Publications 1. Lodén M, Wirén K, Smerud K, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding M. The effect of a corticosteroid cream and a barrier-strengthening moisturizer in hand eczema. A double-blind, randomized, prospective, parallel group clinical trial. JEADV 2012; 26(5): Lodén M, Wirén K, Smerud K, Meland N, Hønnås H, Mørk G, Lützow-Holm C, Funk J, Meding M. Treatment with a Barrier-strengthening Moisturizer Prevents Relapse of Hand-eczema. An open, randomized, prospective, parallel group study. Acta Derm Venerol 2010; 90: Hjalte F, Asseburg C, Tennvall GR. Cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy vs. no treatment after an initial steroid course in patients with atopic dermatitis in Sweden with model applications for Denmark, Norway and Finland. JEADV 2010; 24(4): Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Moisturizers change the mrna expression of enzymes synthesizing skin barrier lipids. Arch Dermatol Res 2009; 301(8): Buraczewska I, Berne B, Lindberg M, Lodén M, Törmä H. Long-term treatment with moisturizers affects the mrna levels of gene involved in keratinocyte differentiation and desquamation. Arch Dermatol Res 2009; 301: Wirén K, Nohlgård C, Nyberg F, Holm L, Svensson M, Johannesson A, Wallberg P, Berne B, Edlund F, Lodén M. Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial. JEADV 2009; 23(11): Buraczewska I, Berne B, Lindberg M, Törmä H, Lodén M. Changes in skin barrier function by long term treatment with moisturizers. Br J Dermatol 2007; 156: Buraczewska I, Lodén M. Treatment of surfactant-damaged skin in humans with creams of different ph. Pharmacology 2005; 73: Lodén M, Bárány E, Mandahl P, Wessman C. The influence of urea treatment on skin susceptibility to surfactant-induced irritation: A placebo-controlled and randomized study. Exogen Dermatol 2004; 3: Lodén M, Kuzima N, Nyrén M, Edlund F, Emtestam L. Nickel susceptibility and skin barrier function to water after treatment with aurea-containing moisturizer. Exog Dermatol 2004; 3: Kuzmina N, Nyrén M, Lodén M, Edlund F, Emtestam L. Effects of pre-treatment an emollient containing urea on nickel allergic skin reactions Acta Derm Venereol 2004; 84: Duval C, Lindberg M, Boman A, Johansson S, Edlund F, Lodén M. Differences among moisturizers in affecting skin susceptibility to hexyl nicotinate, measured as time to increase skin blood flow. Skin Res & Technol 2003; 9: Lodén M, Andersson A-C, Andersson C, Bergbrant I-M, Frödin T, Öman H, Sandström MH, Särnhult T, Voog E, Stenberg B, Pawlik E, Preisler-Häggqvist A, Svensson Å, Lindberg M. A doubleblind study of the effect of glycerine and urea on dry, eczematous skin in atopic patients. Acta Derm Venereol 2002; 82:

35 14. Lodén M, Andersson AC, Andersson C, Frödin T, Öman H, Lindberg M. Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis. Skin Res & Technol 2001; 7: Lodén M, Wessman C. The influence of a cream containing 20 % glycerine and its vehicle on skin barrier properties. Int J Cosm Sc 2001; 23: Lodén M, Andersson A-C, Lindberg M. Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm ). Br J Dermatol 1999; 140: Andersson A-C, Lindberg M, Lodén M. The effect of two urea-containing creams on dry, eczematous skin in atopic patients. I. Expert, patient and instrumental evaluation. J Dermatol Treat 1999; 10: Lodén M, Andersson A-C, Lindberg M. The effect of two urea-containing creams on dry, eczematous skin in atopic patients. II. Adverse effects. J Dermatol Treat 1999; 10: SCIENTIFIC BACKGROUND 19. Lodén M. Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream. Cont Derm 1997; 36: Buraczewska I, Broström U, Lodén M. Artificial reduction in transepidermal water loss improves skin barrier function. Br J Dermatol 2007; 157: Bárány E, Lindberg M, Lodén M. Unexpected skin barrier influence from nonionic emulsifiers. Int J Pharm 2000; 195: Lodén M, Bárány E. Skin identical lipids versus petrolatum in the treatment of tape-stripped and detergent pertubed human skin. Acta Derm Venerol 2000; 80: Lodén M. Urea containing moisturizers influence barrier properties of human skin. Arch Dermatol Res 1996; 288: Lodén M, Andersson AC. Effect of topically applied lipids on surfactant-irritated skin. Br J Dermatol 1996; 134: Lodén M, Hagforsen E, Lindberg M. The presence of body hair influences the measurement of skin hydration with the corneometer. Acta Dermatol Venereol (Stockh) 1995; 75: Lodén M, Olsson H, Axéll T, Linde YW. Friction, capacitance and transepidermal water loss (TEWL) in dry atopic and normal skin. Br J Dermatol 1992; 126: Lodén M, Olsson H, Skare L, Axéll T. Instrumental and sensory evaluation of the frictional response of the skin following a single application of five moisturizing creams. J Soc Cosmet Chem 1992; 43:

36 28. Lodén M. The increase in skin hydration after application of emollients with different amounts of lipids. Acta Derm Venereol (Stockh) 1992; 72: Lodén M, Lindberg M. The influence of a single application of different moisturizers on the skin capacitance. Acta Derm Venereol (Stockh) 1991; 71: Lodén M. The simultaneous penetration of water and sodium lauryl sulfate through isolated human skin. J Soc Cosmet Chem1990; 41: Lodén M, Bengtsson A. Mechanical removal of the superficial portion of the stratum. Corneum by a scrub cream: Methods for the objective assessment of the effects. J Soc Cosmet Chem 1990; 41: QUALITY OF LIFE 32. Halvarsson K, Lodén M. Increasing quality of life by improving the quality of skin in patients with atopic dermatitis. Int J Cosmet Sci 2007; 29(2): SUN PROTECTION 33. Bodekaer M, Akerstrom U, Wulf HC. Accumulation of sunscreen in human skin after daily applications: a study of sunscreens with different ultraviolet radiation filters. Photodermatol Photoimmunol Photomed 2012; 28: Lodén M, Beitner H, Gonzalez H, Edström DW, Akerström U, Austad J, Buraczewska-Norin I, Matsson M, Wulf HC. Sunscreen use: controversies, challenges and regulatory aspects. Br J Dermatol 2011; 165(2): Meijer J, Lodén M. Stability analysis of three UV-filters using HPLC. J Liq Chromatogr 1995; 18: REVIEW ARTICLES AND BOOK CHAPTERS 36. Izabela Buraczewska-Norin, Skin Barrier responses to Moisturizers: Functional and Biochemical Changes, p , In: Treatment of Dry Skin Syndrome: The Art and Science of Moisturizers, edited by Marie Lodén and Howard I. Maibach, Springer, Loden M, Hydrating substances. Pp , In Handbook of Cosmetic Science and Technology, 3rd edition, edited by André O. Barel, Marc Paye, Howard I. Maibach. Informa Healthcare, Lodén M. Urea as a moisturizing and barrier-enhancing ingredient. Pp In: Skin Moisturization, 2nd edition, Ed. Rawlings AV, JJ, Buraczewska I. Skin barrier responses to moisturizers, Acta Universitatis Upsaliensis, Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 381, 66 pp. Uppsala, Lodén M. Prevention or promotion of dryness and eczema by moisturizers? Exp Rev 2008; 3:

37 41. Lodén M, Ungerth L, Serup J. Changes in European Legislation Make it Timely to Introduce a Transparent Market Surveillance System for Cosmetics. Acta Derm Venereol 2007; 87: Halvarsson K, Lodén M. Increasing quality of life by improving the quality of skin in patients with atopic dermatitis. Int J Cosm Sci 2007; 29: Lodén M. Atopic dermatitis and other skin diseases. Pp In: Bioengineering of the Skin: Skin Imaging and Analysis. Ed. Wilhelm KP, Elsner P, Berardesca E, Maibach HI. CRC Press Taylor & Francis Group, Boca Raton Lodén M. Clinical evidence for the use of urea. Pp In: Dry Skin and Moisturizers: Chemistry and function. 2nd ed. Ed: Lodén M. Maibach HI. CRC Press Taylor & Francis Group, Boca Raton, Lodén M. Hydrating substances. Pp In: Handbook of cosmetic science and technology. 2nd ed. Paye M, Barel AO, Maibach HI. CRC Press Taylor & Francis Group, Boca Raton Lodén M, Lindberg M. Moisturizers and irritant contact dermatitis. Pp In: Irritant Dermatitis. Chew A-L, Maibach HI (eds). Springer-Verlag, Berlin Lodén M. The clinical benefit with moisturisers. JEADV 2005; 19: Loden M. Do moisturisers work? J Cosm Derm 2004; 2: Lodén M. Moisturizers. Pp In: Cosmeceuticals and Active Cosmetics. 2nd ed. Elsner P, Maibach HI (eds). 50. Lodén M. Transepidermal water loss and dry skin. Pp , In: Bioengineering and the Skin. Water and stratum corneum. Fluhr J, Elsner P, Berardesca E, Maibach HI. (eds) CRC Press Boca Raton, USA Lodén M. Hydration and Moisturizers. Pp In Bioengineering and the Skin. Water and stratum corneum. Fluhr J, Elsner P, Berardesca E, Maibach HI. (eds) CRC Press Boca Raton, USA Lodén M, Lindberg M. Testing of Moisturizers. Pp In Bioengineering and the Skin. Water and stratum corneum. Fluhr J, Elsner P, Berardesca E, Maibach HI. (eds) CRC Press Boca Raton, USA. 53. Lodén M. Role of topical emollients and moisturizers in the treatment of skin barrier disorders. Am J Clin Derm 2003; 4: Lodén M. The skin barrier and use of moisturizers in atopic dermatitis. Clinics in Dermatology 2002; 21: Lodén M, Edlund F, Jansson T. Strategies to reduce contact allergy to fragrances. Cosmet & Toiletr 2002; 117: Lodén M. Skin barrier function: Effects of moisturizers, Cosmet & Toiletr 2001; 116: Lodén M: Hydrating substances. Pp In: Handbook of cosmetic science and technology. 2nd ed, Ed:, Barel AO, Paye M, Maibach HI. Marcel Dekker, New York,

38 58. Lodén M. Efficacy testing of cosmetics and other topical products. IFSCC Magazine 2000; 3: Lodén M. Hydrating substances. Pp In: Handbook of cosmetic science and technology. Ed: Barel AO, Maibach HI, Paye M. Marcel Dekker, Lodén M. Urea. pp In: Dry skin and moisturizers. Chemistry and function. Eds Lodén M, Maibach HI. CRC Press, Boca Raton, Lodén M. Moisturizers. Pp In: Drugs versus Cosmetics: Cosmeceuticals, Eds Elsner P, Maibach HI. Marcel Dekker, New York, Basel, Lodén M. Keratolytics. Pp In: Dermatopharmacology of topical preparations, Eds Gabard B, Elsner P, Surber C, Treffel P. Springer-Verlag, Rogiers V, Balls M, Basketter D, Berardesca E, Edwards C, Elsner P, Ennen, Leveque JL, Lodén M, Masson P, Parra J, Paye M, Pierard G, Rodrigues L, Schaefer H, Salter D, Zuang V. Non-invasive methods and their potential use in safety assessment of cosmetics. ECVAM-EEMCO Workshop Report 36 ATLA 1999; 27: Lodén M, Linde YW. Atopic dermatitis and other skin diseases. Pp In Bioengineering of the skin: Skin surface imaging and analysis. Eds. Wilhelm KP, Elsner P, Berardesca E, Maibach HI. CRC Press, Boca Raton, Lodén M. Biophysical properties of dry atopic and normal skin with special reference to effects of skin care products. Acta Derm Venerol 1995; suppl 192: Lodén M Biophysical properties of dry atopic and normal skin with special reference to effects of skin care products. Acta Universitatis Upsaliensies, Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 521, 60 pp. Uppsala. 67. Lodén M. Biophysical methods of providing objective documentation of the effects of moisturizing creams. Skin Res Technol 1995; 1: Lodén M, Lindberg M. Product testing. Testing of moisturizers. pp In: Handbooks of Skin Bioengineering, vol. 1. Water and the Stratum corneum, Eds. Elsner P, Berardesca E, Maibach HI. CRC Press, Boca Raton, Lodén M. Detection methods. Pp In: Methods for skin absorption, eds. Kemppainen BW, Reifenrath WG. CRC Press, Boca Raton, BOOKS Lodén M. Ren, mjuk och vacker Kemi och funktion hos kosmetika. 2nd ed, Apotekarsocieteten, Lodén M, Maibach HI. Dry Skin and Moisturizers: Chemistry and function. CRC Press, Boca Raton, Lodén M, Maibach HI. Dry Skin and Moisturizers: Chemistry and function. 2nd ed. CRC Press Taylor & Francis Group, Boca Raton, Lodén M. Ren, Mjuk och Vacker. Kemi och Funktion hos Kosmetika. Apotekarsocieteten,

39