280 research outputs found
Surber, Mrs. R. C. (Etta)
No full textLetter to Mac McGalliard, May 16, 1969. Information on the location of the Dawes school near Berwyn. Letter states it was about two miles north of town on the west side of the Sante Fe tracks. Mrs. Surber lived in Berwyn from 1912 to 1960. 1 page, handwritte
Transmucosal nasal drug delivery : pharmacokinetics and pharmacodynamics of nasally applied esketamine
No full textA study on the epidemiology of rosacea
No full textPharmacoepidemiology is the science of the use and the effects of drugs in large human populations. Although its original role was confined to post-marketing surveillance of rare or long-latency adverse drug events, the science is gaining increasing importance across different stages of drug development, where it has been applied to assess drug utilization patterns and cost-effectiveness, to characterize target populations of drugs in development, to evaluate undiscovered beneficial or detrimental drug effects, or to provide evidence of effectiveness when randomized controlled trials face ethical or practical barriers.
Rosacea is a common but under-investigated inflammatory skin disease, characterized by relapses and remissions. The exact pathomechanism of the skin disease remains to be elucidated, but recent findings indicate a key etiologic role of the innate immune system. Evidence-based treatment options for the skin disease are sparse and greatly needed.
The aim of the comprehensive rosacea project presented within this thesis was to contribute to the general understanding of the skin disease, thereby focusing on the impact of different drugs and diseases on incident rosacea. The project comprises six individual studies, set up in a case-control study design, using data from the General Practice Research Database (GPRD). This United Kingdom (UK)-based database contains longitudinal primary-care records of millions of patients, representative of the UK population. Information is recorded by general practitioners including demographics, lifestyle factors, medical diagnoses, referrals to secondary care, laboratory and diagnostic results, and a complete history of drug prescriptions.
The study population consisted of 53,927 patients with an incident rosacea diagnosis between 1995 and 2009 and the same number of rosacea-free controls, matched on age, sex, index date, general practice, and history in the database. Study 3.1 builds the basis of the project, and describes the study population in terms of demographics, lifestyle characteristics, and ocular symptoms. An overall incidence rate of diagnosed rosacea in the UK of 1.65 / 1,000 person-years was calculated, and stratified by age, gender, calendar time, and geographic region. While cigarette smoking seemed to prevent patients from developing rosacea, alcohol consumption yielded a marginal risk increase.
Studies 3.2 and Study 3.5 fathom the insufficiently supported notion regarding the association of rosacea with migraine (Study 3.2) and with psychiatric diseases (Study 3.5). Drug effects of triptans (Study 3.2) and of psychotropic drugs (Study 3.5) on incident rosacea were also studied. In contrast to previous findings, pre-existing migraine was not generally associated with incident rosacea, but post-menopausal women with severe migraine may be at a slightly increased risk of rosacea. Although mechanistically conceivable, triptans did not alter the risk of developing rosacea. Neither depression nor other affective disorders affected the relative risk of rosacea, but patients with diagnosed schizophrenia were diagnosed with rosacea less frequently. Although the latter finding is intriguing, it requires further investigation, as diagnostic bias cannot be ruled out. Of all psychotropic drugs, current lithium exposure may protect patients from developing the skin disease. Topical lithium has been proven to be effective in seborrheic dermatitis, and might be an interesting approach for rosacea therapy.
Two further studies evaluate the effect of diuretics (focus spironolactone, Study 3.3) and of other antihypertensive drugs (including β-blockers and calcium channel blockers, Study 3.6) on incident rosacea. In line with one previous study, spironolactone yielded a significantly decreased rosacea risk, whereas no other diuretic drug class showed an effect. Despite a generally assumed detrimental effect of calcium channel blockers on rosacea, Study 3.6 did not reveal an increased risk of rosacea for users of this drug class. β-blockers, which have been suggested as an off-label treatment for erythematotelangiectatic rosacea, revealed a small risk decrease, which is probably larger in erythematotelangiectatic rosacea patients alone. Especially with abundantly used therapeutics, such as antihypertensive drugs, sound evidence is required in order for healthcare professionals to make the right decisions in clinical practice.
Finally, Study 3.4 reports a previously uninvestigated decreased rosacea risk for patients with diabetes at an advanced disease stage, potentially due to impaired vasodilation. It remains to be clarified whether insulin enhances this effect.
In summary, these large population-based studies contribute to the understanding of rosacea yielding important evidence and raising new hypotheses. While some results may directly support clinicians in their daily decisions on rosacea treatment, yet others might spark follow-up projects on potential new treatment approaches for rosacea as well as on pathomechanistic aspects of the skin disease
Topical bioavailability of glucocorticosteroids : dermatopharmacokinetic and dermatopharmacodynamic of topically applied triamcinolone acetonide in humans
No full textThe aim of the present thesis was the in vivo investigation of the topical bioavailability of a
model glucocorticosteroid, triamcinolone acetonide (TACA), using tape stripping. The layer by
layer removal of the stratum corneum by tape stripping enables the quantification of drug
amounts penetrated into the stratum corneum over time. This dermatopharmacokinetic (DPK)
approach has been subject of fervent discussions in the past years, and concern about
adequacy and reproducibility of the technique has been expressed. Yet, the successful
performance of reliable and reproducible tape stripping investigations highly depends on the
use of a standardized methodology and suitable analytical methods. This thesis proposed a
standardized tape stripping protocol in combination with carefully validated analytical methods
(Project I). After a proof of concept, the set of methods was applied in an in vivo investigation of
the influence of different factors on topical bioavailability. Both pharmacokinetic and
pharmacodynamic aspects ultimately determining the successful therapy outcome were
investigated: the effect of dose and application frequency (Project II), the effect of occlusion
(Project III), and the efficacy of a low-dose TACA formulation (Project IV). Concomitantly, the
corticosteroid accumulation within the stratum corneum (reservoir development) was monitored,
since a reservoir can considerably affect the therapy outcome and is particularly advantageous
to prevent systemic side effects.
In Project I, the tape stripping technique was standardized and an HPLC method for TACA
quantification on tapes after extraction was validated. The standardized tape stripping protocol
included the use of a template (ensured the removal of stratum corneum samples from the
same skin site) and a hand roller (ensured a constant pressure on the tape before stripping),
and, most importantly, the removal of the entire stratum corneum of one skin site to cope with
inter- and intra-individual differences in stratum corneum thickness. The HPLC method for
TACA quantification was successfully validated and proved to have suitable specificity, linearity,
accuracy, precision, and robustness in the working range. The combination of 1) standardized
tape stripping as sampling method, 2) UV/VIS-spectroscopy for quantification of corneocytes
(previously validated), and 3) the new validated HPLC method for quantification of TACA was
then applied in a proof of concept with 6 healthy volunteers. TACA was applied on their forearm
skin in either an acetonic solution or an ethanolic gel, and stratum corneum samples were
removed by tape stripping after 0.5 h, 3 h, and 24 h. A clear vehicle effect on the TACA
penetration could be observed. Whereas TACA deeply penetrated into the stratum corneum
after application of the acetonic solution, the penetration after application of the ethanolic gel
was only superficial (development of a skin surface reservoir). The method set proved to be
suitable for the investigation of the TACA penetration into stratum corneum and was applied in a
pharmacokinetic clinical trial with healthy volunteers (Projects II and III).
In Project II, the effect of dose and application frequency on the in vivo penetration of TACA
into stratum corneum was investigated in 15 healthy volunteers. Dose and application frequency
of topical corticosteroids are recurrently debated topics. Multiple-daily applications are common,
although a superior efficacy compared to once-daily applications is not unequivocally proven. In
the dose experiment, higher TACA amounts were quantified within the stratum corneum after
application of a high dose (300 mg/cm2 vs. 100 mg/cm2; acetonic solution). However, this
difference was only significant immediately after application, and no difference was recorded at
4 h and 24 h. The application frequency experiment showed slightly higher TACA amounts
within the stratum corneum after multiple application (3x100 mg/cm2) than after single
application of the total dose (1x300 mg/cm2). As a result of multiple applications, the skin was
periodically reloaded with new drug, thus achieving temporary higher amounts within the
stratum corneum and redissolving potential TACA crystals. The still well quantifiable TACA
amount retained within the stratum corneum at 24 h was rather due to the slow diffusion through
the stratum corneum barrier than to a classical reservoir formation. The performance of a mass
balance showed that a high TACA dose could result in faster stratum corneum permeation and
higher systemic exposure, unwelcome in topical therapy. Thus, a low dose applied once daily
may be preferable to higher doses.
In Project III, the effects of occlusion before (pre-occlusion) and after (post-occlusion) TACA
application (100 mg/cm2; acetonic solution) were investigated on the forearms of 10 healthy
volunteers. Occlusion is known to enhance skin hydration and can induce the formation of a
stratum corneum reservoir. Moreover, occlusion is clinically used to improve the efficacy of
topical corticosteroids in severe forms of skin diseases. Pre-occlusion showed no effect on the
TACA penetration into stratum corneum. In contrast, post-occlusion enhanced the TACA
penetration by a factor of 2, favoring the development of a 24 h-lasting reservoir.
The efficacy of low-dose TACA in the treatment of atopic dermatitis was proved in Project IV, a
double-blind, vehicle-controlled, randomized pharmacodynamic explorative study with half-side
comparison in 14 patients. Low-dose TACA was added to a marketed skin care cream
(Lichtena®) in a concentration which was 40 times lower than typical therapeutical corticosteroid
concentrations (25 vs. 1000 μg/g). Twice-daily application of the low-dose TACA formulation
reduced the severity of the lesions (assessed by SCORAD) already after 1 week. In contrast,
the cream base alone had no significant influence on the severity of atopic dermatitis measured
for 1 month. These findings indicate that some corticosteroids may already be effective at much
lower concentrations than usually used therapeutically, and that marketed corticosteroid
formulations may contain a much higher concentration than necessary.
The investigations described in this thesis show how tape stripping, correctly performed, asserts
itself as a valuable technique for topical bioavailability assessment. The DPK approach can be
applied for the investigation of topical bioavailability of other compounds as well, provided that
specific analytical methods for their quantification are developed and validated. Reimplementation
of the DPK approach on regulatory level could be considered
[Jacob Surber]
No full textAnonyme/r Künstler/inDas Blatt könnte im Umkreis von Hans Caspar Waser entstanden seinTitel und Datierung gemäss einer handschriftlichen Notiz auf der Unterlag
A multifaceted perspective on skin cancer prevention
No full textSolar ultraviolet radiation has been acknowledged as the main culprit for the three major
types of skin cancer which are among the most numerous (basal cell carcinoma [BCC],
squamous cell carcinoma [SCC]) and most dangerous (cutaneous malignant melanoma)
malignancies in Caucasian populations.
The present thesis comprises six individual projects providing a multifaceted perspective on
the prevention of these tumours.
Project I evaluated a school-based sun safety education programme developed by the Swiss
Cancer Leagues. Primary school students in the Canton of Zurich (North-Eastern Switzerland)
were asked to answer a questionnaire regarding their sun-related knowledge, behaviour,
and sunburn experience shortly before and one year after the intervention (repeated cross-
sectional assessment). Based on the data from more than 3000 students, the sun safety
education programme was effective in sustainably improving children’s sun-related
knowledge and possibly to some extent in decreasing sunburn rates, but had no obvious
impact on the examined sun protective behaviours (use of sunscreen, seeking shade).
Project II represents a systematic review of cross-sectional and interventional studies on
sun-related knowledge, attitudes, and protective behaviours of outdoor workers. The 52
relevant publications identified through an electronic search of medical literature databases
(PubMed, Embase, PsycINFO) and an extensive hand search suggested that outdoor workers’
sun protective behaviours are largely inadequate and sunburn rates are high (50-80% per
season). However, there is evidence that sun safety education in outdoor occupational
settings is effective in increasing workers’ protective behaviours and presumably also in
reducing sunburn incidence.
Project III investigated sun protective behaviour and sunburn experience of vacationers
spending holidays in the tropics or subtropics. The 1165 standardised face-to-face interviews
conducted among air passengers waiting in the departure or baggage claim area at the
Airport Basel-Mulhouse (Switzerland/France) and among vacationers waiting for pre-travel
health advice at the Travel Clinic of the Swiss Tropical and Public Health Institute Basel
(Switzerland) revealed that almost all respondents used sunscreen at the holiday
destination. Nevertheless, wearing a sunhat and protective clothing as well as seeking shade
were clearly less common sun protection methods. The assessed sunburn rate among the
324 interviewed returning air passengers was alarmingly high, with 44% having suffered
from sunburn during their holiday stay.
Project IV comprehensively analysed the content and quality of 2103 print media articles
pertaining to skin cancer prevention and related topics (solaria, vitamin D) published in
Germany and Switzerland over a one-year period (2012-2013). Whereas skin cancer
secondary prevention received little press attention, primary prevention was a frequently
covered media topic. However, the delivered information was generally rather superficial. By
far the most common and often sole sun protection recommendation made was the use of
sunscreen. In total, 27% of all analysed articles contained misleading or erroneous
statements which were mostly related to the use of sunscreen and vitamin D issues.
Projects V and VI are based on data derived from the Clinical Practice Research Datalink, a
large, well-validated primary care database established in the United Kingdom (UK).
Project V estimated BCC incidence in the UK and characterised affected patients regarding
lifestyle factors and comorbidities. The calculated age-standardised BCC incidence in adults
rose from 119 to 165 per 100 000 person-years between the years 2000 and 2011. According
to the matched case-control analysis including 57 121 BCC cases and 57 121 BCC-free
controls, BCC risk was slightly increased in alcohol drinkers, but reduced in smokers and in
individuals with a body mass index outside the normal range. BCC was associated with
various comorbidities related to iatrogenic or non-iatrogenic immunosuppression.
Project VI explored whether patients regularly exposed to systemic nonsteroidal anti-
inflammatory drugs (NSAIDs) are at a reduced risk of nonmelanoma skin cancer (NMSC). The
matched case-control analysis comprised 65 398 BCC cases, 65 398 BCC-free controls, 7864
SCC cases, and 31 456 SCC-free controls. Overall, NSAID use was not negatively associated
with BCC, but when looking exclusively at users of single NSAID substances there was a
suggestion of a reduced BCC risk in regular users of aspirin and ibuprofen. SCC risk was
slightly decreased in regular users of any NSAIDs, with the strongest risk reduction observed
in current users of coxibs. These findings provide evidence that patients predisposed to
NMSC may benefit from chemoprevention with NSAIDs
[Heinrich Surber aus Niederweningen]
No full textProfilporträt Heinrich SurberAnonyme/r Künstler/inTitel und Datierung gemäss einer handschriftlichen Notiz auf der Unterlag
Between consultancy and advocacy: The politics of anticipating future regulation
No full textSince the 1990s, nanotechnology has served as the “jewel in the crown” of a new research policy regime (Johnson 2004), and as the paradigmatic technology that has spawned new ideas regarding anticipatory governance (Barben et.al. 2008) and responsible innovation (Shelley-Egan and Bowman 2018). Today, man-made nanomaterials are no longer a technology of the future – they are becoming staples of everyday life. Nevertheless, professionals within the field suggest that consumer and investor appetites for such materials are stifled by uncertainties regarding health and safety, as well as regulatory uncertainties. This paper will explore the anticipatory practices of Swedish NGO ChemSec. While portraying itself as an advocacy organisation that was founded by the likes of WWF and the Friends of the Earth, it also fashions itself as a consultancy. Thus, in the context of the above-mentioned uncertainties, it provides a tool called the SIN (“Substitute It Now”) List. This list contains a constantly revised inventory of chemicals and materials that are likely to become subject to future EU regulation. As such, they provide companies with foresight into which chemicals and materials that will become commercial liabilities in the near future. Following previous research on how ChemSec sparked a debate among scientists about the politico-scientific merits of making such claims about the regulatory futures of carbon nanotubes (Surber et.al. 2022), the paper is based on qualitative data on how the NGO operates, how it construes its anticipatory practices, and on how other actors respond to them. Specifically, the paper focuses on how the NGO negotiates the tensions between consultancy and advocacy, and between prediction and performativity. In so doing, the paper engages with recent historical research on how military think tanks have negotiated these tensions (Andersson 2018), as well as with recent anthropological research on how futurist consultancies are involved in similar negotiations. (Garsten and Sörbom 2021) Nevertheless, the case of ChemSec represents an alternative situation, in which the agent of anticipation – an NGO – is pitted against a nanotech industry that holds significant economic and political power, in turn trying to influence another powerful institution: The EU Commission. As such, the paper seeks to engage with the second main theme of the conference (“Politics, Justice and Ethics of Anticipation”), specifically the issue of how power is wielded and negotiated in anticipatory practices. References Andersson, J. 2018. The Future of the World: Futurology, futurists, and the struggle for the post-cold war imagination . Oxford: Oxford University Press. Barben, D., Fisher, E., Selin, C., and Guston, D. 2008. Anticipatory Governance of Nanotechnology: Foresight, Engagement, and Integration. In: EJ. Hackett et.al., eds. The Handbook of Science and Technology Studies , Third Edition. Cambridge, MA: MIT Press. Garsten, C. and Sörbom, A. 2021. Future Fears: Anticipation and the Politics of Emotion in the Future Industry. Culture Unbound , Vol. 13, No. 3. Johnson, A., 2004. The end of pure science: science policy from Bayh-Dole to the NNI. In: D. Baird, A. Nordmann, and J. Schummer, eds. Discovering the nanoscale . Amsterdam; Washington, DC: IOS Press. Shelley-Egan, C. and Bowman, D.M., 2018. Nanotechnologies: the catalyst for responsible research and innovation. In: C. Shelley-Egan and D.M. Bowman, eds. Nanotechnology environmental health and safety . Elsevier. Surber, N., Arvidsson, R., de Fine Licht, K. and Palmås, K. 2022. Implicit values in the recent carbon nanotube debate. (Under review
Evaluierung zellulärer Marker zur Charakterisierung der Schutzleistung von Sonnenschutzprodukten
No full textSummary: Great importance is attributed globally to the protection against UV radiation and the resulting short and/or long-term damaging effects on the human skin. Increasing skin-cancer rates demonstrate the urgency of a broad-spectrum protection of the skin against sunlight and an extensive information and behavioural training for the population. Unlike earlier formulations (between 1985 and 2000), current sunscreen products contain UV filter combinations, with broader protection in the UVB and UVA range of the solar spectrum. The efficacy of the products is expressed by the sun protection factor (SPF) (in vivo determination), which is a measure of the protection against the development of erythema. However, SPF only characterises the protective performance in the UVB range. Determination of SPF is performed exclusively on humans, is time-consuming and expensive and is accompanied by the damaging of the skin of volunteers. Additionally the link between erythema and the development of skin cancer is not completely understood. The UVA protection capacity of a sun protection product can also be determined and the compliance with all requested EU recommandations is indicated with the UVA logo. The UVA protection factor (UVA-PF) can be determined with an accepted in vitro method. There is a worldwide research for additional parameters for characterizing the protective performance of sunscreen products.
The objective of the present work was the development of an in vitro test system to characterize the protective performance of formulations already during the development phase. In this context, markers suitable for the characterization of UV-induced damage are evaluated at cellular levels. Different cellular localisations, such as extracellular matrix, cytoplasmic range and nucleic region should be considered in the selection of potential cell damage markers.
Cytokines (interleukin 1a and interleukin 8), p38-MAPK, p53, and cyclobutane pyrimidine dimers (CPD) have been analysed experimentally as potential markers. Normal human keratinocytes (HNK) and immortalised HaCaT cells served as models and were exposed to UV radiation. Assay techniques such as ELISA and/or flow cytometry (FACS) were used for read-out evaluation.
The kinetics and dose-response relationships were determined for each marker in individual preliminary tests. Two of the five markers tested, delivered no reproducible results. The experiments performed with cytokines as potential cell damage markers were regarded as unsuitable due to the high divergence in the measurement values, and were not followed up.
In order to evaluate the selected test systems, different sunscreen products (SPF 5 to 50+) were analyzed. The products were applied to PMMA platelets and the latter were attached to the cell culture dishes. Following UV exposure the markers were quantified.
In the case of p38-MAPK, after exposure to a dose of 200 mJ/cm2 UVB and subsequent incubation period of 30 minutes, the maximal activation of p38 was 2.2 ± 0.29. The protective performance of five sunscreen products (SPF between 5 und 50+) was characterized with the established p38-MAPK assay. All the products differed significantly in the amount of activated p38-MAPK compared to the positive control (no protecting product). By means of the SPF only a subdivision of the products into a SPF 5 group and a SPF 16 to 50+ group could be achieved.
The maximal measured increase in p53 protein after exposure to 100 mJ/cm2 UVB and subsequent incubation period of 6 hours was 1.5 ± 0.01. The results of the experiments with sunscreen products were comparable to those found with p38-MAPK. Two sunscreen products with SPF 50+ and 25, as well as the COLIPA Standard P3 (SPF 16) differed hardly from the non-exposed negative control in terms of their p53 protein concentrations. Solely the formulation with pure UVA protection with a low SPF of 5 differed from the other test products. Hence, also with p53 as cell damage marker, merely two groups were achieved: 1) Products with a high, medium and low SPF (SPF 16 to 50+) and 2) Products with a very low SPF (SPF 5).
The only UV-specific marker were the CPD. For the determination of the CPD an ELISA assay as well as a FACS assay could be established. The exposure dose used, was 828 mJ/cm2 with a subsequent incubation period of two hours. Both assays exhibited comparable results, whereby the ELISA, with a maximal detected increase of factor 30 in the CPD amount proved to be more sensitive. The analysis technique FACS produced a maximal increase of factor 8. Eight out of a total of thirteen tested sunscreen products were trade brands and five were development formulations, specifically compounded for these test purposes. The results from the experiments with CPDs as markers allowed a more detailed classification of the products by means of their SPFs. Three groups were compiled with the FACS quantification: 1) Products with high and medium SPF (SPF 25 to 50+), 2) Products with low SPF (SPF 16) and 3) Products with very low SPF (SPF 5). The classification using the ELISA Assay also resulted in three groups: 1) Products with very high and high SPF (SPF 30+ to 50+), 2) Products with medium SPF (SPF 25 and 30) and 3) Products with low and very low SPF (SPF 5 and 16). The experiments with the development formulations, revealed, that under the used test conditions CPDs mainly occur as a result of UVB influence, confirming the predominant opinion in the literature.
An in vitro test system could be established from three of the five potential markers, whereat the CPD quantification was best suitable for classification of the protective performance of sunscreen products. However these DNA dimers are no replacement for SPF, since they are also mainly UVB-specific, nevertheless there is a better known link between DNA damage and the development of cancer compared to erythema.
The determination of the cyclobutane pyrimidine dimers in the developed experimental set-up appears suitable for determining the protective performance of sunscreen products already in an early development phase. Therefore the assay provides an important screening instrument for developers of sunscreen products. ---------- Zusammenfassung: Zusammenfassung: Dem Schutz vor UV-Strahlung und den daraus resultierenden kurz- und/oder langfristigen, schädlichen Einflüssen auf die menschliche Haut, kommt weltweit eine wachsende Bedeutung zu. Steigende Hautkrebsraten zeigen die Dringlichkeit eines umfassenden Schutzes der Haut vor Sonnenstrahlung, sowie einer umfassenden Information und Verhaltensschulung der Bevölkerung auf. Aktuelle Sonnenschutzprodukte enthalten, im Gegensatz zu früheren Formulierungen (zwischen 1985 und 2000), Filterkombinationen, die einen breiteren Schutz im UVB- und UVA-Bereich des Sonnenlichtspektrums aufweisen. Die Wirksamkeit der Produkte wird primär über den Sonnenschutzfaktor (SPF) (in vivo Bestimmung), der ein Mass für den Schutz vor Erythementstehung darstellt, ausgedrückt. Der SPF charakterisiert allerdings nur die UVB-Schutzleistung des Produktes. Die Bestimmung des SPF erfolgt ausschliesslich am Menschen, ist aufwändig, teuer und geht mit einer bewusst in Kauf genommenen Schädigung der Haut der Probanden einher. Hinzu kommt, dass der Zusammenhang zwischen Erythem und Hautkrebsentstehung nicht vollständig geklärt ist. Der UVA-Schutz einer Formulierung kann ebenfalls bestimmt werden und die Erfüllung bestimmter Kriterien wird durch das EU UVA-Logo gekennzeichnet. Der UVA-Schutzfaktor (UVA-PF) kann mit Hilfe einer akzeptierten in vitro Bestimmungsmethode ermittelt werden. Weltweit wird nach weiteren Kenngrössen für die umfassende Charakterisierung der Schutzleistung von Sonnenschutzprodukten gesucht.
Das Ziel der vorliegenden Arbeit war die Entwicklung eines in vitro-Testsystems, das bereits in der Entwicklungsphase von Formulierungen zur Charakterisierung der Schutzleistung eingesetzt werden könnte. Dabei sollen auf zellulärer Ebene Marker evaluiert werden, die sich zur Charakterisierung einer UV-bedingten Schädigung eignen würden. Bei der Auswahl möglicher Zellschadenmarker sollten verschiedene Zelllokalisationen, wie extrazelluläre Matrix, zytoplasmatischer Bereich und Kernregion berücksichtigt werden.
Als mögliche Marker wurden Zytokine (Interleukin 1a und Interleukin 8), die p38-MAPK, p53, sowie Cyclobutan Pyrimidin Dimere (CPD) experimentell untersucht. Als Modell dienten humane normale Keratinozyten (HNK) und immortalisierte HaCaT-Zellen, die einer UV-Bestrahlung ausgesetzt wurden. Zur Analyse der Marker wurden Assay-Techniken wie ELISA und/oder Durchflusszytometrie (FACS) eingesetzt.
Die Kinetiken und Dosis-Effektbeziehungen wurden für jeden Marker in Vorversuchen bestimmt. Zwei der fünf untersuchten Marker lieferten keine reproduzierbaren Ergebnisse. Die Arbeit mit Zytokinen als mögliche Zellschadenmarker erwies sich aufgrund der Messvarianzen als ungeeignet und wurde nicht weiterverfolgt.
Zur Evaluierung der ausgewählten Testsysteme wurden exemplarisch verschiedene Sonnenschutzprodukte (SPF 5 bis 50+) eingesetzt. Die Produkte wurden auf Plexiglasplatten (PMMA-Platten) aufgetragen und diese auf den Kulturbehältnissen der Zellen befestigt. Anschliessend erfolgten die Bestrahlung mit UVB, sowie die Quantifizierung der Marker.
Bei der p38-MAPK fand sich nach einer Bestrahlung mit der Dosis von 200 mJ/cm2 UVB und einer anschliessenden Inkubationszeit von 30 Minuten eine maximale p38-Aktivierung um den Faktor 2.2 ± 0.29. Die Schutzleistung von fünf Sonnenschutzprodukten mit SPF zwischen 5 und 50+ wurde mit dem p38-MAPK-Assay charakterisiert. Alle Produkte unterschieden sich in der Menge an aktivierter p38-MAPK statistisch signifikant von der Positivkontrolle (ohne schützendes Produkt). Anhand des SPFs konnte jedoch nur eine Unterteilung der Produkte in eine Gruppe SPF 5 und eine Gruppe SPF 16 bis 50+ gemacht werden.
Die maximal gemessene Steigerung an p53-Protein betrug nach einer Bestrahlung mit 100 mJ/cm2 UVB und einer darauf folgenden Inkubationszeit von 6 Stunden 1.5 ± 0.01. Die Ergebnisse der Experimente mit Sonnenschutzprodukten waren vergleichbar mit denjenigen mit p38-MAPK als Marker. Zwei Sonnenschutzprodukte mit SPF 50+ und 25, sowie der COLIPA Standard P3 (SPF 16) unterschieden sich in ihren p53-Proteinkonzentrationen kaum von der unbestrahlten Negativkontrolle. Einzig die reine UVA-Schutzformulierung mit einem tiefen SPF von 5 unterschied sich von den anderen Testprodukten. Somit konnten auch bei p53 als Zellschadenmarker lediglich zwei Gruppen ermittelt werden: 1) Produkte mit hohem, mittlerem und tiefem SPF (SPF 16 bis 50+) und 2) Produkte mit sehr tiefem SPF (SPF 5).
Der einzige UV-spezifische Marker waren die CPD. Zur Bestimmung der CPD konnten sowohl ein ELISA-Assay, als auch ein FACS-Assay etabliert werden. Die verwendete Bestrahlungsdosis betrug 828 mJ/cm2 mit einer anschliessenden Inkubationszeit von zwei Stunden. Beide Assays lieferten in ihrer Aussage vergleichbare Resultate, wobei sich der ELISA mit einer maximal detektierten Steigerung der CPD-Menge um Faktor 30 als sensitiver erwies. Die Analysetechnik FACS ergab eine maximale Steigerung um den Faktor 8. Von den dreizehn untersuchten Sonnenschutzprodukten waren acht Handelsprodukte und weitere fünf für diese Testzwecke selbst hergestellte Entwicklungsformulierungen. Die Ergebnisse aus den Experimenten mit CPDs als Marker liessen eine detailliertere Aufteilung der Produkte anhand ihres SPFs zu. Mit der FACS-Quantifizierung konnten drei Gruppen erstellt werden: 1) Produkte mit hohem und mittlerem SPF (SPF 25 bis 50+), 2) Produkte mit tiefem SPF (SPF 16) und 3) Produkte mit sehr tiefem SPF (SPF 5). Die Klassierung anhand der ELISA-Resultate resultierte ebenfalls in drei Gruppen: 1) Produkte mit sehr hohem und hohem SPF (SPF 30+ bis 50+), 2) Produkte mit mittlerem SPF (SPF 25 und 30) und 3) Produkte mit tiefem und sehr tiefem SPF (SPF 5 und 16). Aus den Versuchen mit den Entwicklungsformulierungen konnte zudem die Erkenntnis gewonnen werden, dass CPDs bei den verwendeten Testbedingungen dieser Arbeit hauptsächlich durch UVB-Einfluss entstehen, was die in der Literatur vorherrschende Meinung bestätigte.
Von drei der fünf potentiellen Markern konnte ein in vitro-Testsystem etabliert werden, wobei sich insbesondere das Testsystem der CPD-Quantifizierung als geeignet für eine Klassierung der Schutzleistung von Sonnenschutzprodukten darstellte. Die DNA-Dimere sind in dieser Form zwar kein Ersatz für den SPF, da auch sie vor allem UVB-spezifisch sind, allerdings besteht zwischen DNA-Schädigungen und der Krebsentstehung ein besser bekannter Zusammenhang, als das beim Erythem der Fall ist.
Die Bestimmung der Cyclobutan Pyrimidin Dimere in der entwickelten Testanordnung erscheint geeignet um die Schutzleistung von Sonnenschutzprodukten bereits in der frühen Entwicklungsphase zu bestimmen. Durch diese Möglichkeit wird dem Entwickler von Sonnenschutzprodukten ein wichtiges Screeninginstrument in die Hand gegeben
Maryland Terrapin volleyball team, 1995
No full textMaryland Terrapin volleyball team, 1995. Caption reads: "FRONT ROW (L to R): TANIA NAGL, EDEN KROEGER, MONEACH SURBER, KIM MOSLEY, SHANTELLE JOHNSON, DAUNE KOESTER. BACK ROW (L to R): HEAD COACH JANICE KRUGER, ASSISTANT COACH PAUL SCHEEL, CARRIE JAECK, JAIME SUMMERS, CONYA JABARI-KITWALA, SHANNON SALTZMAN, SHERRY SMITH, LAURA CRESSA, CANDACE SEITZ, ASSISTANT COACH FELIX HOU, MANAGER JASON FAJARDO, MANAGER JOE GOBLE.
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