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Biomedical subjects

A Fullerton

Publications and source records attributed to A Fullerton.

At least 19 recordsLinked to original sources

The hairless guinea-pig as a model for treatment of cumulative irritation in humans.

BACKGROUND: The effect of six skin-care formulations (SCFs) on experimentally induced cumulative irritation was studied in hairless guinea-pigs (HLGPs) and in human volunteers (HVs). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10% isopropyl palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola oil cream) or 0.5% (-)-alpha-bisabolol (bisabolol cream). METHODS: In HLGP, irritant dermatitis was induced with 30 min daily exposure for 4 days to 0.5% sodium lauryl sulfate aq. (SLS). In HVs, irritant dermatitis was induced with 10 min daily exposure for 5+4 days (no irritation on weekends) to 3% SLS aq. on the right and 30% nonanoic acid (NON) in n-propanol on the left volar forearm. Clinical scoring was performed daily; evaporimetry (total epidermal water loss (TEWL)), hydration and colorimetry were measured at baseline (day 0) in the middle and at the end of treatment. Treatments were applied twice daily. The basic cream and the IPP cream were excluded from testing in HLGP because they were known from previous studies to be irritant in HLGP, while all formulations were known to be equally and well tolerated locally in humans. RESULTS: All formulations worsened the skin irritation in HLGP: the glycerol cream the least, the canola oil cream the most, while the bisabolol cream and the carbomer cream were indistinguishable. In humans, the glycerol cream was better than 'No Treatment' after cumulative irritation with both SLS and NON. The basic cream was better tolerated in humans than was expected from previous testing in HLGPs. CONCLUSION: In conclusion, the results from the studies in HLGPs and HVs are in agreement with regard to ranking of the SCFs. Further, the glycerol cream showed a positive treatment effect on both SLS- and NON-irritated skin in HVs.

Administration, Topical↗

The hairless guinea-pig as a model for treatment of acute irritation in humans.

BACKGROUND: The effect of six skin care formulations on experimentally induced acute irritation was studied in hairless guinea-pigs (HLGP) and in human volunteers (HV). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10% isopropyl palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola oil cream) or 0.5% (-)-alpha-bisabolol (bisabolol cream). METHODS: Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate aq. in both HLGP and HV, and in HV also by using nonanoic acid in n-propanol (NON) 20%. The irritant reactions were treated twice daily with the formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments was performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colorimetry. RESULTS: The glycerol cream was the only product showing effects potentially better than no treatment in HV. CONCLUSION: The HLGP was too sensitive an animal model as a predictor for effect in humans. There was no difference in efficacy of the formulations against the two different irritants in HV.

Animals↗

Guidelines for visualization of cutaneous blood flow by laser Doppler perfusion imaging. A report from the Standardization Group of the European Society of Contact Dermatitis based upon the HIRELADO European community project.

This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

Humans↗

The calcipotriol dose-irritation relationship: 48 hour occlusive testing in healthy volunteers using Finn Chambers.

Calcipotriol is widely used in the treatment of psoriasis. Adverse lesional and perilesional irritation may occur. Allergy may occasionally be suspected. Allergy patch testing with calcipotriol may be difficult or impossible because calcipotriol is a local irritant. The aim of the present study was to assess the calcipotriol dose-irritation relationship, and establish a non-irritant patch test concentration for calcipotriol allergy patch testing. The study was a prospective, double-blind, randomized, dose titration evaluation in 180 healthy volunteers never previously exposed to calcipotriol. All individuals were patch tested with a calcipotriol dilution series (range 0.016-250 micrograms/mL). Clinical reading of test sites and measurement of erythema using a Minolta ChromaMeter were performed on days 2 and 3. Laser Doppler perfusion imaging of cutaneous blood flow was performed on day 3. Doubtful reactions (score 1/2) and weak reactions (score 1) were frequent and observed even at low dose exposure. Reactions declined in strength between the readings on day 2 and day 3. Only score 2 reactions with moderate erythema and some infiltration showed a threshold of no irritation. This threshold was confirmed by colorimetry and flowmetry. Cases of suspected allergy to calcipotriol may to avoid irritant reaction and false positive readings, be patch tested with calcipotriol 2 micrograms/mL citrate-buffered isopropanol solution applied under occlusion for 48 h using small Finn Chambers. Score 1/2 and 1 reactions are likely to reflect irritation. A positive test should be repeated after a minimum period of 3 months to ensure its consistency over time. A repeated open application test may be indicated.

Adolescent↗

Characterization of irritant patch test reactions to topical D vitamins and all-trans retinoic acid in comparison with sodium lauryl sulphate. Evaluation by clinical scoring and multiparametric non-invasive measuring techniques.

The study was a single-centre, double-blind randomized, placebo-controlled within-subject comparison of 42 healthy volunteers. Occlusive patch test for 48 h was performed with solutions of 1 alpha,25(OH)2D3 (calcitriol), two vitamin D analogues (calcipotriol and KH 1060 (lexacalcitol)), all-trans retinoic acid and sodium lauryl sulphate (SLS) as reference irritant. Solution vehicles and an empty chamber was also included. Test evaluation was performed at day 2, day 3 and again on day 7. Test evaluation was based both on clinical scoring and on various non-invasive measuring methods. 1 alpha,25(OH)2D3, calcipotriol and KH 1060 all showed mild irritation in the concentrations tested. The number and severity of test reactions was found to be dose dependent based both on clinical scoring and on non-invasive measurements. Irritation of the vitamin D analogues mainly affected the vasculature with vasodilation and increased cutaneous blood flow. All-trans retinoic acid showed irritant reactions with some similarity to the tested vitamin D analogues; however, the reactions were more prolonged. Transepidermal water loss (TEWL) was affected neither after application of vitamin D analogues nor after application of all-trans retinoic acid and it was thus concluded that these substances are non-corrosive. SLS showed the known irritant mechanism with corrosion and increase in TEWL as the primary event.

Adult↗

Topical D-vitamins: multiparametric comparison of the irritant potential of calcipotriol, tacalcitol and calcitriol in a hairless guinea pig model.

The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D3 (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a hairless guinea pig model, Randomized, occlusive patch testing for 2 days was used. Each group of 8 animals was tested simultaneously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5 micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of the patches) and again at day 3. Evaluation was blinded and based on a multiple parameter assessment of skin irritancy, comparing clinical scoring, skin perfusion using high resolution laser Doppler image scanning, skin colour (a*, Minolta ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Skin biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential for calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical irritation score, cutaneous blood flow, skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was dominated by vasodilation and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TEWL remained unaffected. The hairless guinea pig appears a valid model to test irritancy of topical D-vitamins since the same profile of irritancy was previously established in humans for 2 of the compounds tested, calcitriol and calcipotriol.

Administration, Topical↗

Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis.

This report reviews individual-related variables (age, sex, race, anatomical site, skin surface properties), intra- and interindividual variation (temporal, physical and mental activity, orthostatic effect, menstrual cycle/menopause), environment-related variables (light conditions, temperature) and various instrument-related variables that influence skin colour. CIE colorimetry (Minolta Chroma Meter) and spectrophotometric measurement (Derma Spectrometer) are considered. The guidelines give recommendations for measuring conditions and procedures.

Adult↗

Patch test study with calcipotriol ointment in different patient groups, including psoriatic patients with and without adverse dermatitis.

One hundred and sixty-eight individuals (psoriatic patients treated with calcipotriol with dermatitis due to calcipotriol, psoriatic patients treated with calcipotriol with no dermatitis, psoriatic patients never treated with calcipotriol, patients with eczema and healthy volunteers) were patch-tested (Finn chambers, back, 48 h) with dilutions of calcipotriol ointment (50, 10, 2, 0.4 micrograms/g) and an ointment vehicle. Test evaluation was based on clinical scoring and various non-invasive measuring methods. Doubtful (?+) and weak (1+) reactions were common, irrespective of patient group and history. Moderate (2+) reactions were uncommon and with no increased frequency among psoriatic patients with adverse dermatitis during calcipotriol treatment. The blood flow of test sites measured by laser Doppler flowmetry was, however, increased in psoriatics, who developed dermatitis during calcipotriol treatment as an isolated finding. Furthermore a 1-week repeated open application test (ROAT) was performed on all subjects. None of the persons having a strong reaction in the patch test showed any dermatitis in the ROAT test, indicating that they were not sensitized. Calcipotriol was found to be a mild irritant of the non-corrosive type, i.e. with no influence on the skin barrier. Reactions were dominated by redness (increased laser Doppler flow and chroma a*) and only oedema formation in advanced reactions. The calcipotriol dose-irritation curve was found to be scattered. Calcipotriol induced no increase of transepidermal water loss (TEWL) versus the ointment vehicle, but the ointment vehicle itself increased TEWL. The special ointment vehicle needed for calcipotriol for stability reasons may itself be irritant and cause some impairment of the skin water barrier, with increase in TEWL values. Future patch test studies for calcipotriol allergy should not be done with this vehicle. The non-irritant threshold concentration of calcipotriol in an appropriate test vehicle is still unknown.

Adult↗

In vitro and in vivo evaluation of the effect of barrier gels in nickel contact allergy.

The protective effect of various ethylenediaminetetraacetate (EDTA) barrier gels on nickel skin penetration was investigated in an in vitro model using human skin. Application of the gels seemed to cause an increased release of nickel from nickel alloys. This nickel did not penetrate the skin barrier but was found to be immobilized on the skin surface. This emphasized the importance of washing the skin surface to remove any surplus of barrier formulation after use, since considerable amounts of nickel will be bound in this formulation. It was found that application of the barrier gels beneath the nickel alloy in contact with the skin significantly reduced the amount of nickel found in the epidermal skin layer. In vivo patch testing with a disc of nickel alloy, with and without use of barrier gel, was performed in 21 nickel-sensitive patients. Patch testing with the nickel alloy without use of barrier gel resulted in positive patch test reactions in 11/21 (52.4%) of the patients tested. Application of a Carbopol gel with 10% CaNa2-EDTA beneath the nickel disc completely abrogated the allergic contact response in all 21/21 (100%) patients. A Carbopol gel without CaNa2-EDTA was less effective, inhibiting the response in 15/21 (71.4%). A high concordance was found between epidermal nickel levels found in vitro and the in vivo patch test.

Breast↗

Sodium lauryl sulphate penetration in an in vitro model using human skin.

Because of their ability to impair the skin barrier function, detergents constitute a major risk factor for the development of irritant contact dermatitis. Sodium lauryl sulphate (SLS) is a commonly used detergent for experimental studies within the area of irritant contact dermatitis. In the present study, penetration of S35-labelled SLS was studied in an in vitro model using human cadaver skin. The investigations showed that SLS is capable of permeating the skin barrier when applied under occlusion. SLS could be detected in the dermis and the amount of SLS found here was shown to depend on the dose of SLS applied on the skin. Penetration of SLS continued after removal of the SLS applied as a patch test on the skin surface. Considerable inter-individual variation in the penetration of SLS was demonstrated between different donors.

Adult↗

Chromium content in human skin after in vitro application of ordinary cement and ferrous-sulphate-reduced cement.

The amount of chromium found in human skin after in vitro application of cement suspensions on full-thickness human skin in diffusion cells was investigated. Cement suspensions made from ordinary Portland cement or Portland cement with the chromate reduced with added ferrous sulphate were used. The cement suspensions were either applied on the skin surface under occlusion for 48 h or applied repeatedly every 24 h for 96 h. No statistically significant difference in chromium content of skin layers between skin exposed to ordinary Portland cement, skin exposed to cement with added ferrous sulphate and unexposed skin was observed, despite a more permeable skin barrier at the alkaline pH of the cement suspensions, i.e., pH 12.5. Increased chromium levels in epidermis and dermis were seen when ordinary Portland cement was applied as a suspension with added sodium sulphate (20%) on the skin surface for 96 h. The content of water-soluble chromium in ordinary Portland cement may vary due to the alkali sulphate content of the cement.

Cementation↗

Permeation of chromium salts through human skin in vitro.

Chromium permeation studies were performed on full thickness human skin in diffusion cells. All samples were analysed for the total chromium content by graphite furnace Zeeman-corrected atomic absorption spectrometry. Some samples were analysed by an ion chromatographic method permitting the simultaneous determination of Cr(VI) and Cr(III) as well. The amounts of chromium found in all skin layers were significantly higher when potassium dichromate was applied to the skin compared with chromium chloride or chromium nitrate. Chromium could only be detected in the recipient phase after application of the dichromate solution. Chromium skin levels increased with increasing concentrations of applied chromium salts up to 0.034 M Cr. The amount of chromium in recipient phase and skin layers increased with increasing pH when the applied solution contained potassium dichromate. This was ascribed to a decreased skin barrier function of the skin. The amount of chromium found in all skin layers after application of chromium chloride decreased with increasing pH due to lower solubility of the salt. The % of chromium found in the recipient phase as chromium(VI) increased with increasing total chromium concentration indicating a limited reduction ability of the skin in vitro.

Chlorides↗

Irritant patch testing: penetration of sodium lauryl sulphate into human skin.

To clarify the sources of variation in irritant patch testing, variability in delivery of the test substance from the patch test system was studied. An in vitro model was used to study the penetration of sodium lauryl sulphate (SLS) from a patch test system into the skin. Different formulations of SLS applied to the skin for 24 h were studied (aqueous solution and gels), but irrespective of the vehicle used permeation of SLS into the recipient phase was poor. Results were compared to in vivo patch testing in 12 subjects. Approximately 70% of the applied SLS in aqueous solution was released from the patch test system. Release from gels was poorer. High concordance between the in vivo and the in vitro model was found. No correlation was found between the amount of SLS left in the filter disc and the strength of the clinical reaction in vivo.

Adult↗