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Biomedical subjects

Peter Elsner

Publications and source records attributed to Peter Elsner.

At least 55 records · Page 3Linked to original sources
PubMed2004

Melatonin suppresses reactive oxygen species induced by UV irradiation in leukocytes.

An investigation of the antioxidative UV protective effect of melatonin was performed in an in vitro irradiation model with leukocytes. Leukocytes were isolated from EDTA-treated whole blood and taken up in phosphate-buffered saline (PBS). Five of 10 aliquots were incubated with 2 mmol/L melatonin and 5 with PBS as a control. The samples were irradiated by UV light (280-360 nm, max: 310 nm) at doses between 75 and 300 mJ/cm(2) or left unirradiated. Radical formation was measured using the chemiluminescence technique. Staining with trypan blue was performed to assess cell viability. Melatonin significantly suppressed radical formation in cell solutions irradiated from 75 to 300 mJ/cm(2) (P </= 0.001). Controls showed an increase of reactive oxygen species (ROS) formation as a sign of oxidative stress when irradiated with increasing UV doses and a maximum ROS formation under 300 mJ/cm(2) UV light. The cytotoxicity of UV light was reduced by melatonin up to a UV dose of 1.5 J/cm(2). Leukocytes were suitable cells for the evaluation of the efficacy of melatonin as a radical scavenger under UV light. The results confirm that the clinically observed UV protective effects of melatonin may be at least partially based on its radical scavenging properties.

Antioxidants↗
PubMed2004

Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine in human and mouse dendritic cells.

Dendritic cells (DC) are specialized antigen presenting cells characterized by their ability to migrate into target sites and secondary lymphoid organs in order to process antigens and activate naive T cells. Previously, we have shown that several secretion products from platelets and mast cells such as histamine, sphingosine-1-phosphate (S1P), and lysophosphatidic acid (LPA) have chemotactic activity towards immature human DC. Furthermore, they limit the capacity of mature human DC to initiate and amplify T helper cell type 1 (Th1) immune responses by inhibition of interleukin (IL)-12 and upregulation of IL-10 secretion. In this study we focused on the effect of these agents on murine DC. In murine DC no influence on IL-10 and IL-12 release by these agents was observed. Moreover, histamine and LPA failed to stimulate chemotaxis and actin reorganization in mouse DC. Instead, S1P had chemotactic activity and induced actin polymerization in immature as well as mature mouse DC. Therefore, our in vitro data implicate that in contrast to humans the function and immunological capacity of murine DC are not so tightly controlled by mast cell and platelet-derived secretion products such as histamine, S1P and LPA. These findings suggest that mouse models might underestimate the complex regulative network between mast cells, platelets and DC.

Actins↗
PubMed2003

Effects of electrostimulation on glycogenolysis in cultured rat myotubes.

A model for electrostimulation causing contractions of primary cultures of rat myotubes was established. The kinetics of glycogen degradation was investigated for a 2-h period to elucidate the coupling between contraction and glycogenolytic flux. Electrostimulation caused contraction and increased glycogenolytic flux, but had no effect on glycogen phosphorylase-a activity. Forskolin increased glycogenolytic flux more than electrostimulation, and caused a fast activation of glycogen phosphorylase, while it did not elicit contraction. The effects of electrostimulation and forskolin on glycogenolytic flux were partly additive. The metabolism of glucose and glycogen was almost equally anaerobic and aerobic. The ATP content remained constant during glycogenolysis, but phosphocreatine decreased with the largest decrease in electrostimulated cells. The calculated ATP turnover rate increased about 3 times by electrostimulation. For all conditions, pHi decreased from about 7.0 to about 6.6 at 2 h. It is concluded that in the present in vitro system glycogenolytic flux may be enhanced without eliciting contraction, a condition normally not observed in vivo. The system also shows much less dynamic range of energy metabolism than in vivo, primarily because of a high resting ATP turnover.

Adenosine Triphosphate↗
PubMed2003

Randomized clinical trials for psoriasis 1977-2000: the EDEN survey.

This study aims to describe the range of treatment comparisons, study designs and quality of reporting of randomized clinical trials (RCTs) in psoriasis published in a variety of medical and dermatological journals, and to analyze time trends with quality items. Hand-searching of clinical trials of psoriasis published from 1977 to 2000 in 13 medical or dermatological journals, selected as relevant to a European readership, was performed. A total of 249 trials published in 226 papers were classified as RCTs. Of these, 139 (55.8%) employed a parallel control group design, 107 (43.0%) studies adopted a self-control design and 3 (1.2%) a cross-over design. The median number of patients recruited per study was 40 (range 6-699). Overall, 55 different treatment modalities, including topical, ultraviolet-based, systemic, and other miscellaneous therapies were assessed. Only 31 (12.5%) RCTs were comparative studies of treatment modalities in different therapeutic classes. Most of the studies were short-term with a median study duration of 7 weeks (range 1-104), with only 18 studies (7.2%) lasting for more than four months. A variety of outcome measures including 44 different score systems were employed. According to the conclusions of the authors, 196 (78.7%) studies were judged to provide striking or definite observations in favor of one of the treatments examined. No important variations over time were documented for quality items. Based on our survey we have identified an enormous range of treatments that have been evaluated for psoriasis over the examined period. Most studies were short-term, and only a handful compared treatment options in different therapeutic classes. Since we did not examine all the relevant journals, the number of treatment options may be even greater than we have documented. There is an urgent need to reset the research agenda focusing on long-term comparative RCTs. Editors of major medical and dermatological journals are urged to take a role in improving the quality of RCT reporting.

Clinical Trials as Topic↗
PubMed2003

Ultraviolet a induces generation of squalene monohydroperoxide isomers in human sebum and skin surface lipids in vitro and in vivo.

At the outermost surface of human skin, skin surface lipids are first-line targets of solar ultraviolet radiation. Therefore, we hypothesized that ultraviolet A and ultraviolet B irradiation induce photo-oxidation of skin surface lipids. To test this, sebum samples were collected from facial skin of 17 healthy volunteers, weighed, and immediately irradiated with either ultraviolet B or ultraviolet A. Squalene, the major sebum lipid, as well as photo-oxidation products were identified in sebum lipid extracts by high-performance liquid chromatography analysis. Upon ultraviolet A exposures squalene was depleted in a concentration-dependent manner, whereas an unidentified sebum lipid photo-oxidation product was detected. Using high-performance thin layer chromatography, high-performance liquid chromatography, atmospheric pressure chemical ionization mass spectrometry, and nuclear magnetic resonance, unidentified sebum lipid photo-oxidation product was identified as a mixture of squalene monohydroperoxide isomers. Squalene monohydroperoxide isomers purified from sebum were identical with squalene monohydroperoxide isomers synthesized by preparative photo-oxidation of squalene. Squalene monohydroperoxide isomers were formed even after small suberythematogenic doses of ultraviolet A (5 J per cm2). Whereas physiologic baseline levels of squalene monohydroperoxide isomers in human skin were only slightly above detection limits, squalene monohydroperoxide isomer levels were strongly increased by suberythematogenic doses of ultraviolet A both in vitro and in vivo. High-performance liquid chromatography results could be complemented by a straightforward thin layer chromatography method for rapid screening of lipid peroxide formation in human sebum/skin surface lipids. In conclusion, specific squalene monohydroperoxide isomers were identified as highly ultraviolet A sensitive skin surface lipid breakdown products that may serve as a marker for photo-oxidative stress in vitro and in vivo.

Adult↗
PubMed2003

A comparative study on the skin penetration of pure tryptanthrin and tryptanthrin in Isatis tinctoria extract by dermal microdialysis coupled with isotope dilution ESI-LC-MS.

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has recently been identified as a pharmacologically active compound in Isatis tinctoria, with potent dual inhibitory activity on prostaglandin and leukotriene synthesis. To investigate the skin penetration of tryptanthrin from solutions of pure compound and Isatis extracts, we developed and validated a cutaneous microdialysis model using ex vivo pig foreleg. Microdialysis was performed by placing linear probes in the dermis of the skin in situ, and tryptanthrin concentrations in the dialysates were determined by isotope dilution electrospray ionization LC-MS in the selected ion mode. Measurable concentrations of tryptanthrin were detected 30 min after application. A dose-dependent increase in tryptanthrin concentrations in the dialysate was observed for the Isatis extracts, but not for pure tryptanthrin. Microscopic analysis showed that the pure compound crystallized from the solution but remained in an amorphous state in the extracts.

Animals↗
PubMed2003

The role of H2O2 as a mediator of UVB-induced apoptosis in keratinocytes.

Apoptosis is an active form of cell death that is initiated by a variety of stimuli, including reactive oxygen species (ROS) and ultraviolet (UV) radiation. Previously, it has been reported that UVB-irradiation of keratinocytes leads to intracellular generation of hydrogen peroxide (H2O2) and that antioxidants can inhibit ROS-induced apoptosis. Although both UVB-irradiation and H2O2-incubation led to increased intracellular H2O2 levels, the antioxidants catalase and glutathione monoester (GME), inhibited apoptosis only when induced by H2O2, not by UVB. Furthermore, extracellular signal-regulated kinase (ERK), a prominent member of the mitogen-activated protein kinase (MAPK) family, was found to be activated by treatment with both UVB and H2O2. Inhibition of ERK phosphorylation by pre-treatment with PD98059 resulted in enhanced apoptosis after H2O2-exposure. However,no significant difference of apoptosis was observed between cells with and without inhibitor pre-treatment upon UVB-irradiation. DNA damage in the form of cyclobutane pyrimidine dimers was observed after exposure to UVB, but no photoproducts were found in H2O2-treated cells. These results suggest a ROS-independent pathway of UVB-induced apoptosis. Although UVB-irradiation causes moderate increase in H2O2, the generation of H2O2 does not contribute to the induction of apoptosis. Moreover, activation of ERK only blocks H2O2-dependent apoptosis but has no impact on UVB-induced apoptosis.

Antioxidants↗
PubMed2003

Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide.

Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. In rare cases, severe skin reactions up to the extreme expression of toxic epidermal necrolysis have been observed. A female patient with rheumatoid arthritis had been treated with systemic steroids and methotrexate for 2 years. Five weeks prior to admission to our hospital methotrexate was replaced by leflunomide. Three weeks after initiation of leflunomide therapy a progressive generalized erythema with blistering formation occurred accompanied by increase of body temperature, chills and erosive lesions on the lips and oral mucosa. The palmar and plantar surfaces revealed edema, erythema and pulpitis with epidermolysis. On histologic examination necrotic keratinocytes and epidermal spongiosis were observed. After administration of high-dose prednisolone and topical treatment the patient recovered within 14 days. This is one of the few cases of severe drug reaction after intake of leflunomide. Therefore, the indication of this relatively new drug should be considered carefully.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Evidence of involvement of CXC-chemokines in proliferation of cultivated human melanocytes.

The CXC-chemokines 1 and 8 (CXCL1 and CXCL8) are ligands for the G protein-coupled CXC-chemokine receptor 2 (CXCR2). Both chemokines and CXCR2 are components of a potent autocrine growth factor loop in human melanoma cells. Currently, expression and biological function of both chemokines in normal human melanocytes is poorly defined. Here we describe that cocktails of melanocyte growth factors consisting of basic fibroblast growth factor (bFGF), endothelin 1 (ET-1) and alpha-melanocyte-stimulating hormone (alpha-MSH) stimulated release of CXCL1 and CXCL8, but did not influence expression of CXCR2 in human melanocytes. Cell studies revealed that CXCL1 and CXCL8 potentiate the proliferative activity of various combinations of cocktails with growth factor such as bFGF, ET-1 and alpha-MSH. Moreover, ligand blocking anti-CXCR2 antibodies reduced proliferation of melanocytes after stimulation with bFGF, ET-1 and alpha-MSH. This study implicates that CXCL1, CXCL8 and their receptor CXCR2 are components of an autocrine mechanism in proliferating human melanocytes.

Cell Division↗
PubMed2002

Prevention of hand dermatitis in bakers' apprentices: different efficacy of skin protection measures and UVB hardening.

OBJECTIVE: The objective of this controlled intervention study was to quantify the efficacy of skin protection (SP) measures and ultraviolet B (UVB) hardening in the prevention of hand dermatitis in bakers' apprentices. METHOD: SP measures were compared against UVB hardening in a controlled clinical trial of 94 apprentices. The apprentices were assigned to the intervention arms class-wise. Bakers' apprentices involved in a previous follow-up study served as additional controls representing no intervention. The apprentices were interviewed and examined in a standardised way at the beginning of the training and at 4 monthly follow-ups. Transepidermal water loss (TEWL) was measured at the back of the hands. RESULTS: Demographic profile and atopy criteria were equally distributed in the two intervention arms and the control group. Point prevalence of hand dermatitis after 6 months was highest in the controls (29.1%) followed by the UVB (19.4%) and the SP group (13.3%). UVB hardening and SP measures reduced hand dermatitis prevalence by 9.7% (95%CI: -8.5 to 28.1) and 15.7% (95%CI: -2.4 to 33.9), respectively. Application of SP measures reduced the odds ratios (ORs) for hand dermatitis 0.8-fold (95%CI: 0.17-3.70) and 0.33-fold (95%CI: 0.09-1.23) compared with the UVB group and the controls, respectively. These clinical trends were confirmed by statistically significant differences in TEWL values. TEWL values were consistently higher in the UVB group than in the SP group ( P=0.002). CONCLUSIONS: This study provided evidence, based on significant differences in TEWL levels, that general SP measures may be more effective than UV light hardening of the skin, which in turn was more effective than no intervention. This trend was supported by the frequency of development of clinical hand dermatitis, although differences did not reach statistical significance. A multi-centre trial is recommended to confirm the efficacy of SP measures in a larger randomised study.

Adolescent↗
PubMed2002

Skin protection in bakers' apprentices.

Skin protection measures - barrier creams, protective gloves - and skin care are widely recommended for the prevention of occupational hand dermatitis (HD) in skin risk professions, but there is hardly anything known about uptake levels of the measures. The objective of this controlled intervention study was to quantify the uptake and maintenance of skin protection and skin care measures in first-year bakers' apprentices. A total of 94 first-year bakers' apprentices were included in the study in September 2000. The apprentices were assigned to the skin protection and control group class-wise to reduce contamination. The skin protection group comprised 39 apprentices who were trained in skin protection measures at the beginning and after 4 weeks of training. 55 apprentices were assigned to the control group representing no skin protection intervention. Standardized interviews took place at the beginning of the training and at 4 monthly follow-ups (FU). The uptake of skin protection measures differed significantly between the groups (barrier cream p < 0.0001, protective gloves p = 0.046, skin care p = 0.025). Barrier cream use in the skin protection group was incorporated in the daily routine very well from the start and reached 100% at the end of the examination period (4th FU). At this time, only 3.2% of the controls used barrier creams. The level of acceptance of protective gloves (4th FU: skin protection group 43.3%; controls 32.3%) was considerably lower than that of barrier creams. The initial level of regular skin care was high in both groups (skin protection group 67.6%, controls 61.7%). After the intervention the acceptance of skin care rose to 88.9% in the skin protection group compared to 68.1% in the controls (4th FU). The present study has shown that skin protection and skin care measures can be introduced successfully in the daily routine of a skin risk occupation and high uptake and maintenance rates can be achieved.

Adolescent↗
PubMed2002

Fragrance contact dermatitis - a worldwide multicenter investigation (Part III).

The purpose of this study was to determine the frequency of responses to selected fragrance materials in patients who were fragrance sensitive. 218 fragrance sensitive subjects were evaluated in eight centres worldwide with a fragrance mixture (FM) and 17 less well-studied fragrance materials. Reaction to the fragrance mixture (FM) occurred in 76% of the subjects. The (FM) detected all reactions to nerol and hydroxycitronellol and 93% of the reactions to clove bud oil. Ten fragrance materials were not detected by the FM and deserve further study: benzenepropanol, beta, beta, 3-trimethyl, hexyl-salicylate, dl-citronellol, synthetic ylang ylang oil, benzyl mixture, cyclohexyl-acetate, eugenyl methyl ether, isoeugenyl methyl ether, 3-phenyl-1-propanol, and 3, 7-dimethyl-7-methoxyoctan-2-ol.

Adult↗