Ludger Kolbe - Academia.edu (original) (raw)

Papers by Ludger Kolbe

Photodermatology, Photoimmunology and Photomedicine, Nov 17, 2019

Life on earth is strongly depending on solar radiation. However, solar radiation can also cause s... more Life on earth is strongly depending on solar radiation. However, solar radiation can also cause severe damage as a function of intensity and wavelength. In the last decades, photobiological research focused on the deleterious effects of ultraviolet (UV) light with the highest photon energy and the biggest impact on skin although the UV waveband accounts for only 5% of the solar spectrum. 1 It is well established that cellular damage, in particular by UVA, is mediated through the generation of reactive oxygen species (ROS) in sun-exposed skin. At the opposite end of the solar spectrum, investigations

Experimental Dermatology, Feb 9, 2017

Age spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented l... more Age spots, also called solar lentigines and lentigo senilis, are light brown to black pigmented lesions of various sizes that typically develop in chronically sun-exposed skin. It is well known that age spots are strongly related to chronic sun exposure and are associated with photodamage and an increased risk for skin cancer, however, the mechanism(s) underlying their development remain poorly understood. We used immunohistochemical analysis and microarray analysis to investigate the processes involved in their formation, focusing on specific markers associated with the functions and proliferation of melanocytes and keratinocytes. A total of 193 genes were differentially expressed in age spots but melanocyte pigment genes were not among them. The increased expression of keratins 5 and 10, markers of basal and suprabasal keratinocytes, respectively, in age spots suggests that the increased proliferation of basal keratinocytes combined with the decreased turnover of suprabasal keratinocytes leads to the exaggerated formation of rete ridges in lesional epidermis which in turn disrupts the normal processing of melanin upwards from the basal layer. Based on our results, we propose a model for the development of age spots that explains the accumulation of melanin and the development of extensive rete ridges in those hyperpigmented lesions.

Individual data set of subjects in this single-center, double-blind, randomized, split-face, cont... more Individual data set of subjects in this single-center, double-blind, randomized, split-face, controlled clinical trial. The study was conducted over the course of 12 weeks in order to assess the efficacy and tolerance of a Thiamidol-containing topical formulation in comparison to a sunscreen only control (Cell A) and against an over-the-counter (OTC) 2% hydroquinone formula (Cell B) when used by women with bilateral dyspigmentation from melasma. Parameters evaluated (over the course of 12 weeks of use, compared with baseline scores/values and between products): - changes in melasma area and severity index (MASI) - subjective assessment by the subjects - tolerability evaluation (erythema, edema, burning, stining, itching tingling

Skin Research and Technology, May 1, 1999

... Querleux et al., using MRI with an in-depth pixel resolution of 70 pm, were able to visu-aliz... more ... Querleux et al., using MRI with an in-depth pixel resolution of 70 pm, were able to visu-alize the epidermis and stratum corneum on ... Ethnic d rfferences The volar and dorsal forearms of Caucasian subjects (phototype II) were compared with those of an African-American and an ...

Scientific Reports, Jul 31, 2020

The simultaneous analysis of different regulatory levels of biological phenomena by means of mult... more The simultaneous analysis of different regulatory levels of biological phenomena by means of multi-omics data integration has proven an invaluable tool in modern precision medicine, yet many processes ultimately paving the way towards disease manifestation remain elusive and have not been studied in this regard. Here we investigated the early molecular events following repetitive UV irradiation of in vivo healthy human skin in depth on transcriptomic and epigenetic level. Our results provide first hints towards an immediate acquisition of epigenetic memories related to aging and cancer and demonstrate significantly correlated epigenetic and transcriptomic responses to irradiation stress. The data allowed the precise prediction of inter-individual UV sensitivity, and molecular subtyping on the integrated post-irradiation multi-omics data established the existence of three latent molecular phototypes. Importantly, further analysis suggested a form of melanin-independent DNA damage protection in subjects with higher innate UV resilience. This work establishes a highresolution molecular landscape of the acute epidermal UV response and demonstrates the potential of integrative analyses to untangle complex and heterogeneous biological responses. Solar UV irradiation has complex and ambivalent effects on the human organism. Beneficial effects of sun exposure are thought to be mainly mediated by vitamin D, which is synthesized in the skin through a photosynthetic reaction triggered by exposure to UVB. Vitamin D was primarily acknowledged for its importance in bone formation, increasing evidence however points to its influence on the proper functioning of nearly every tissue in our bodies 1. In contrast to this however, solar UV irradiation is also the most abundant risk factor for skin cancer and other extrinsically influenced skin disorders 2,3. It is well established that UV irradiation both directly and indirectly induces DNA damage. Direct damage is mainly a result of UVB and to lesser extent UVA irradiation, causing dimerization of adjacent pyrimidine bases, a frequent cause of mutations during replication 4. Indirect DNA damage results mainly from oxidative stress, caused by free radicals and cellular reactive oxygen species, which increase after UV irradiation 5. Damaged DNA, if not properly repaired, interferes with many cellular mechanisms such as transcription, the cell cycle and replication and can give rise to mutations and epigenetic alterations, driving genomic instability and ultimately carcinogenesis. Human skin has developed several defense systems to guard against the damaging effects of UV: Prominently these include structural changes to the tissue such as epidermal thickening and the synthesis of melanin, but they also comprise quick molecular adaptations like the suspension of cell cycle and gene transcription, as well as the activation of DNA repair pathways. The extent of protection afforded by these mechanisms however is characterized by high inter-individual variation 6. The stratification of individual UV response is thus highly important for risk assessment in cancer prevention (UV-protection), therapeutic dose determination (PUVA therapy) and in the understanding of the biological processes leading to malignancies (e.g. squamous skin cancers). Fitzpatrick skin type categories 7 have been widely used as an indicator and predictor of sun sensitivity in epidemiology and experimental photobiology. However, this categorization is hampered by subjectivity and is prone to recall

Journal of Cosmetic Dermatology, Dec 1, 2008

SummaryBackground Subclinical, chronic tissue inflammation involving the generation of cytokines... more SummaryBackground Subclinical, chronic tissue inflammation involving the generation of cytokines (e.g., interleukin‐6 and tumor necrosis factor‐alpha) might contribute to the cutaneous aging process.Aims This study aims to screen for an active ingredient with anti‐inflammatory (i.e., reduction of interleukin‐6 and tumor necrosis factor‐alpha) and matrix‐stimulating efficacy which improves the clinical signs of skin aging in vivo.Patients/methods In vitro studies with pure Arctiin were performed investigating the inhibition of cytokine induction and stimulation of collagen neosynthesis. In vivo home‐in‐use studies using an Arctium lappa fruit extract–containing formulation were carried out to determine procollagen and hyaluronan synthesis, hyaluronan synthase‐2 gene expression, and reduction of wrinkle volume after treatment.Results In vitro studies on human dermal fibroblasts and monocyte‐derived dendritic cells supplemented with pure Arctiin showed relative to untreated control cells a stimulation of collagen synthesis and a decrease in interleukin‐6 and tumor necrosis factor‐alpha concentration, respectively. In addition, topical in vivo application of an A. lappa fruit extract–containing formulation for 12 weeks significantly stimulated procollagen synthesis and increased hyaluronan synthase‐2 expression as well as hyaluronan levels compared to vehicle‐treated control areas. Similarly, after a 4‐week treatment with an A. lappa fruit extract–containing formulation, wrinkle volume in the crow's feet area was significantly reduced as compared to treatment with the vehicle.Conclusions Our data show that topical treatment with a natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo. In conclusion, A. lappa fruit extract represents a targeted means to regenerate dermal structures and, thus, offers an effective treatment option for mature skin.

Journal of Biophotonics, Jan 26, 2021

The current method for determining the sun protection factor (SPF) requires erythema formation. N... more The current method for determining the sun protection factor (SPF) requires erythema formation. Noninvasive alternatives have recently been suggested by several groups. Our group previously developed a functional sensor based on diffuse reflectance measurements with one UVB LED, which was previously evaluated on pig ear skin. Here we present the results of a systematic in vivo study using 12 sunscreens on 10 volunteers (skin types [ST] I‐III). The relationship of the UVB‐LED reflectance of unprotected skin and melanin index was determined for each ST. The spatial variation of the reflectance signal of different positions was analyzed and seems to be mainly influenced by sample inhomogeneity except for high‐protection factors (PFs) where signal levels are close to detection noise. Despite the low‐signal levels, a correlation of the measured LED‐based UVB PF with SPF reference values from test institutes with R2 = 0.57 is obtained, suggesting a strong relationship of SPF and LED‐based UVB‐PF. Measured PFs tend to be lower for increasing skin pigmentation. The sensor design seems to be suitable for investigations where a fast measurement of relative changes of PFs, such as due to inhomogeneous application, bathing and sweating, is of interest.

Journal of Dermatology, Oct 21, 2021

Thiamidol® was the most potent inhibitor of human tyrosinase out of 50 000 screened substances. I... more Thiamidol® was the most potent inhibitor of human tyrosinase out of 50 000 screened substances. In vivo, it was well tolerated and improved melasma significantly. This was the first 24‐week, randomized, double‐blind, vehicle‐controlled, cosmetic clinical study to assess the efficacy and tolerability of thiamidol in moderate‐to‐severe melasma of phototype III–V subjects with subsequent regression phase. Females allocated to verum (n = 23), applied daily Dual Serum followed either by Day Care SPF30 in the morning or by Night Care in the evening, all containing Thiamidol. The vehicle group (25 females) followed the same skin care routine using the corresponding vehicle formulations. Subjects came back for a follow‐up visit 13–20 weeks after treatment (regression phase). Assessments included clinical photography, Melasma Area and Severity Index (MASI), skin lightness, quality of life, and tolerability. Baseline demographics and hyperpigmentation were well balanced across the treatment groups. Clinical photography and MASI improved with Thiamidol significantly versus baseline (p < 0.001) and vehicle (p < 0.001–0.043) at all time points up to treatment end. At follow‐up, the MASI was still significantly lower than at baseline but similar for verum and vehicle. Skin lightness and quality of life improved significantly versus baseline without significant differences between verum and vehicle. This study demonstrated that Thiamidol is well tolerated and superior in improving melasma compared to baseline and vehicle over a treatment period of 24 weeks.

Journal of Biophotonics, Nov 14, 2020

The sun protection factor (SPF) values are currently determined using an invasive procedure, in w... more The sun protection factor (SPF) values are currently determined using an invasive procedure, in which the volunteers are irradiated with ultraviolet (UV) light. Non‐invasive approaches based on hybrid diffuse reflectance spectroscopy (HDRS) have shown a good correlation with conventional SPF testing. Here, we present a novel compact and adjustable DRS test system. The in vivo measurements were performed using a multi‐lambda‐LED light source and an 84‐channel imaging spectrograph with a fiber optic probe for detection. A transmission spectrum was calculated based on the reflectance measured with sunscreen and the reflectance measured without sunscreen. The preexposure in vitro spectrum was fitted to the in vivo spectrum. Each of the 11 test products was investigated on 10 volunteers. The SPF and UVA‐PF values obtained by this new approach were compared with in vivo SPF results determined by certified test institutes. A correlation coefficient R2 = 0.86 for SPF, and R2 = 0.92 for UVA‐PF were calculated. Having examined various approaches to apply the HDRS principle, the method we present was found to produce valid and reproducible results, suggesting that the multi‐lambda‐LED device is suitable for in‐vivo SPF testing based on the HDRS principle as well as for in‐vivo UVA‐PF measurements.

Journal of Cosmetic Dermatology, Sep 1, 2006

SummaryBackground Patients with rosacea and red facial skin often show sensitivity to skin care ... more SummaryBackground Patients with rosacea and red facial skin often show sensitivity to skin care products which can exacerbate inflammation and subjective irritation. Besides pharmacologic management, special skin care is prudent to avoid cosmetically induced irritation and address cosmetic concerns. Appropriate skin care should provide gentle cleansing, UVA/UVB protection, effective moisturization, and concealing pigments to neutralize the appearance of redness.Aims To evaluate skin compatibility and efficacy of a skin care regimen containing licochalcone A (Lic A), an anti‐irritant from the licorice plant Glycyrrhiza inflata, for subjects with mild to moderate facial redness.Patients/methods Sixty‐two patients with mild to moderate red facial skin used a four‐product skin care regimen for 8 weeks. Clinical assessments of erythema and subjective irritation, cross‐polarized photography, and self‐assessment questionnaires were completed at baseline, and after 4 and 8 weeks of use. A quality of life questionnaire was given at baseline and week 8.Results Clinical evaluations, subject response, and photography confirmed very good tolerability of the regimen and effective neutralization of redness by the pigmented products. Significant improvements in average erythema scores were observed at 4 and 8 weeks (P < 0.05), and an improvement in quality of life was confirmed by the patient questionnaires.Discussion The skin care regimen containing Lic A was found to be compatible with the sensitive facial skin of patients with rosacea and improved the appearance of persistent facial redness. The products were also observed to be compatible with daily metronidazole treatment.

Journal of the American Academy of Dermatology, 2021

Until recently, the primary focus of photobiology has centered on the impact of UV radiation on s... more Until recently, the primary focus of photobiology has centered on the impact of UV radiation on skin health, including DNA damage and oncogenesis; however, the significant effects of visible light (VL) on skin remains grossly underreported. VL has been reported to cause erythema in light skin, Fitzpatrick skin types (FST) I-III, and pigmentary changes in individuals with darker skin types, FST IV-VI. These effects have importance in dermatologic diseases and potentially play a role in conditions aggravated by sun exposure, including phototoxicity in FST I-III patients and post-inflammatory hyperpigmentation and melasma, in FST IV-VI patients. Induction of free radicals leading to generation of reactive species is one driving mechanism of VL-induced skin pathologies, leading to induction of melanogenesis and hyperpigmentation. Initial clinical studies have demonstrated effectiveness of topical sunscreen with antioxidant combinations in inhibiting VL+UVA1- induced erythema in FST I-III and reducing pigmentation in FST IV-VI. Antioxidants may help prevent worsening of pigmentary disorders and can be incorporated into photoprotective strategies. It is essential that dermatologists and the public are aware of the impact of VL on skin, especially in patients of skin of color, and understand the available options for VL protection.

Verwendung von einem oder mehreren Wirkstoffen aus der Gruppe Tetrahydrocurcumin, Tetrahydrodemet... more Verwendung von einem oder mehreren Wirkstoffen aus der Gruppe Tetrahydrocurcumin, Tetrahydrodemethoxycurcumin und Tetrahydrobisdemethoxycurcumin zur Herstellung kosmetischer oder dermatologischer Zubereitungen zur Verbesserung der Barrierefunktion der Haut.

International Journal of Cosmetic Science, 2020

In 2017, Cosmetics Europe performed a double‐blinded ring test of 24 emulsion‐type sunscreen prod... more In 2017, Cosmetics Europe performed a double‐blinded ring test of 24 emulsion‐type sunscreen products, across 3 in vivo test laboratories and 3 in vitro test laboratories, using a new candidate in vitro SPF test method. Based on the results of this work, an article was published showing how data derived from a new lead candidate method conform to new International Standards (ISO) acceptance criteria for alternative SPF test methods (Any alternative method should consider the matrix effect and if required, specify the matrix applicability of the method; Criterion 1a: Systematic differences between methods should be negligible: 95% of all individual results of an alternative method are within the range of ±2× reproducibility standard deviation of the in vivo method, that is overall bias must be below 0.5× reproducibility standard deviation of the in vivo method; Criterion 1b: Measurement uncertainty of an alternative method should be below the measurement uncertainty of the in vivo me...

Journal of Investigative Dermatology, 2019

Melasma is a pigmentary disorder characterized by hyperpigmented patchy skin in sun-exposed areas... more Melasma is a pigmentary disorder characterized by hyperpigmented patchy skin in sun-exposed areas, especially the face. Treatment of melasma can be challenging because long-term therapy is required, reoccurrence is common, and existing therapies are insufficient and unsatisfactory. To investigate new treatment options, we performed an exploratory double-blinded, randomized split-face study to assess the efficacy of the tyrosinase inhibitor Thiamidol compared to hydroquinone in women with mild to moderate melasma. After 12 weeks, modified Melasma Area and Severity Index scores significantly improved on both the Thiamidol-treated and the hydroquinone-treated sides of the face. Additionally, Thiamidol treatment improved modified Melasma Area and Severity Index scores significantly better than hydroquinone, and more subjects improved following treatment with Thiamidol (79%) compared with hydroquinone (61%). During treatment, no subjects displayed worsening of modified Melasma Area and Severity Index scores on the Thiamidol-treated side, while approximately 10% of the subjects showed a worsening of modified Melasma Area and Severity Index scores on the hydroquinone-treated side. All subjects routinely used sunscreens and consistent results were obtained in low and in high UV ambient conditions. Subjects rated the efficacy of the Thiamidol formulation significantly better with regard to overall decreased intensity of dark spots and their overall appearance throughout the study. Thiamidol was well-tolerated and well-perceived and represents an effective agent to reduce hyperpigmentation.

Pigment Cell & Melanoma Research, 2018

Exposure to excess ultraviolet (UV) A radiation induces the degradation/modification of both eume... more Exposure to excess ultraviolet (UV) A radiation induces the degradation/modification of both eumelanin and pheomelanin that may be deleterious to pigmented tissues. Although the spectral distribution of solar energy comprises nearly half of visible light (VL), few studies have been conducted to examine the role of VL in the photodegradation of both types of melanin, either VL alone or in combination with UVA. In this study, we examined the effects of physiological doses of VL (150 to 300 J/cm 2) alone or in combination with a physiological dose of UVA (20 J/cm 2) in normal human epidermal melanocytes. The degradation/modification of melanin structures were evaluated by our chemical degradation-HPLC methods. The results show that VL accelerates UVA-induced changes in the structural features of both eumelanin and pheomelanin, although VL or UVA alone induced only minor changes in melanin structure. The differential spectral method provides support for the additive effects of VL.

Pigment cell & melanoma research, 2017

International Journal of Cosmetic Science, 2012

A multicentred study derived from the COLIPA in vitro UVA method was performed to assess the infl... more A multicentred study derived from the COLIPA in vitro UVA method was performed to assess the influence of test conditions on UVA protection factor (UVAPF) values in terms of amplitude, reproducibility between laboratories and correlation with in vivo UVA results. Eight products with a range of in vivo UVAPF from three to 29 were used. Two different types of plates, namely high-roughness (5 μm) and low-roughness (2 μm) plates, were used with a different application rate for each (1.3 mg cm(-2) and 0.75 mg cm(-2) respectively). The UVR dose applied to both plate types followed the same principle as the original test (1.2 J. cm(-2) × UVAPF0). Strong, significant correlations between in vitro and in vivo UVAPF values were observed for both plate types (Pearson correlation > 0.9, P ≤ 0.01). The correlation and slope obtained with the low-roughness plates confirmed the previous results obtained by COLIPA. Across all laboratories, higher UVAPF values were obtained on the high-roughness plates (P < 0.01). Reproducibility of UVAPF values between laboratories was comparable between the two plate roughness values (low roughness, COV = 8%; high roughness, COV = 12%). Considering the in vitro/in vivo comparisons, a regression slope of 0.83 was observed for the low-roughness plates, in comparison with a value of 1.05 for the high-roughness plates. The accuracy of the method was improved, therefore, with the use of the high-roughness plates. With a constraint to recommend the use of only one plate type in the COLIPA UVA in vitro Test, the high-roughness plate was selected on an on-going basis to limit variability of results and to provide better accuracy with in vivo data.