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Biomedical subjects

J Serup

Publications and source records attributed to J Serup.

At least 19 recordsLinked to original sources
PubMed2002

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↗
PubMed2002

The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats.

There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans.

Administration, Topical↗
PubMed2002

Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a randomized, double-blind, placebo-controlled study of histamine and other inducers of itch.

BACKGROUND: Investigations of pruritogenic substances in humans have involved intradermal injections in normal skin; itching of inflamed skin has been little studied. OBJECTIVES: To develop an itch model with provocation of itch in experimentally inflamed skin as well as in normal skin, using subjects as self-controls. METHODS: In 32 non-atopic volunteers aged 21-30 years, the skin of five selected test sites on one volar forearm was pretreated for 24 h with large Finn chambers containing 1% sodium lauryl sulphate (SLS) used as a standard contact irritant to induce inflammation. Twenty microlitres of different pruritogenic substances [histamine, substance P, neurokinin A, neurokinin B, trypsin, platelet-activating factor (PAF) and serotonin] and saline as control were injected intradermally into the inflamed test sites and in corresponding non-treated sites on the opposite forearm. The test individuals scored itch intensity on a visual analogue scale for 20 min, and weal area was then measured. : RESULTS: Histamine and substance P induced itch in both normal and inflamed skin compared with a saline reference. Neurokinin A, trypsin, PAF and serotonin only elicited itch in normal skin, and neurokinin B neither elicited itch in normal skin nor in inflamed skin. Itch was induced in normal and SLS-inflamed skin to a similar magnitude. However, weal area after histamine was significantly (P < 0.001) larger in inflamed skin when compared with normal skin. CONCLUSIONS: Histamine and substance P elicited itch to the same degree in normal skin and inflamed skin pretreated with SLS despite a stronger weal response in inflamed skin. Mediators present in inflamed skin did not potentiate itch, a c-fibre-mediated neuronal response. The weal reaction is based on enhanced vascular permeability (protein extravasation). A greater skin perfusion in inflamed skin may therefore have increased the weal size. We propose an experimental model in humans for testing of itch involving both normal and inflamed skin. The model has the potential for use in evaluating new topical and systemic treatments of itch.

Adult↗
PubMed2002

Topically applied aspirin decreases histamine-induced wheal and flare reactions in normal and SLS-inflamed skin, but does not decrease itch. A randomized, double-blind and placebo-controlled human study.

Topically applied aspirin has recently been reported to decrease histamine-induced itch in human volunteers. Our aim is to confirm this and to study the antipruritic ability of topical aspirin in inflamed skin. In 24 non-atopic volunteers, an inflammatory skin reaction was induced in forearm skin at 5 different sites by sodium lauryl sulphate contained in Finn Chambers. Aspirin 10%, aspirin 1%, mepyramine 5% and vehicle were applied to the inflamed and corresponding non-inflamed areas 20 min before itch induction with intradermal histamine injection. Itch and pain were scored on a visual analogue scale at regular intervals. Wheal and flare areas were measured. No difference in itch intensities was found after application of aspirin, mepyramine and vehicle, but more itch was induced in aspirin and mepyramine pretreated sites in inflamed skin compared to normal skin (p<0.05). In normal skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.05) and mepyramine (p<0.001), as were wheal areas after mepyramine (p<0.01), compared to vehicle pretreatments. In inflamed skin, flare areas were smaller after pretreatment with aspirin 10% (p<0.01) and mepyramine (p<0.001), as were wheal areas after aspirin 10% (p<0.01), aspirin 1% (p<0.05) and mepyramine (p<0.001). We conclude that despite a significant skin penetration as measured by the influence on wheal and flare reactions, topically applied aspirin did not decrease histamine-induced itch in the model used.

Administration, Topical↗
PubMed2001

Comparison of two pH meters used for skin surface pH measurement: the pH meter 'pH900' from Courage & Khazaka versus the pH meter '1140' from Mettler Toledo.

BACKGROUND/AIMS: Measurement of skin surface pH is used in clinical research to evaluate hazardous shifts in pH following external exposures and to evaluate the state of diseased skin with acute or chronic changes. It is therefore important to measure skin surface pH as precisely as possible. The aim of this study was to compare two commercially available pH meters used for skin surface pH measurement, to reveal differences between them in measured skin pH on the forearm. METHODS: The first pH meter (pH900) had a pointed electrode and a stabilisation period of 3 s. The second pH meter (pH meter 1140) had a circular electrode and no fixed stabilisation period. Twelve healthy subjects (6 male and 6 female Caucasians) entered the study. The pH measurements were performed once an hour from 8 a.m. to 3 p.m. on both forearms in five areas from the elbow to the "wristwatch" zone. In each area, three measurements were performed next to each other with both pH meters (15 measurements per arm per hour per pH meter). RESULTS: The pH900 has a higher measuring level and a higher variation than the pH meter 1140. CONCLUSION: A skin surface pH meter with a circular electrode and with no fixed stabilisation period is preferable. It is recommended that the pH meter be allowed to stabilise for at least 7 s before the result is read.

Female↗
PubMed2001

Females have lower skin surface pH than men. A study on the surface of gender, forearm site variation, right/left difference and time of the day on the skin surface pH.

BACKGROUND/AIMS: It is of great interest to describe the many functions and properties of the skin in order to better understand reactions that result in different skin abnormalities, as a prerequisite in the development of skin products and topical medicines. Skin surface pH is considered a critical parameter of skin wellbeing and is typically studied on the forearm skin. Despite many previous investigations, this is an extensive field that still needs a great deal of research. The aim of our study was to investigate gender related differences, differences between right and left arms, anatomical variation and daytime variation in skin surface pH. METHODS: Skin surface pH was measured on the flexor surface of the forearm on eleven healthy volunteers (6 men and 5 women). A Mettler Toledo pH meter (pH meter 1140) was used. The subjects were measured once every hour from 8 a.m. to 3 p.m. in five areas from the elbow to the wrist. In each of the five areas, three measurements were performed next to each other, and the mean of these was used in subsequent calculations. RESULTS: A statistically significant difference in skin pH between men (mean pH=5.80) and women (mean pH=5.54) was found, with women being more acidic than men (P<0.01). No difference between right and left arm was found. In men, the area closest to the wrist had significantly lower pH values compared with the proximal sites. This was not the case in women. Skin surface pH decreased during normal working hours in both genders. CONCLUSION: Spontaneous skin surface pH was found to be significantly lower in women, as compared to men--albeit, the difference was small and of unknown relevance. Nevertheless, comparative studies on skin surface pH should be balanced with respect to gender. There appeared to be no right/left difference and no systematic change during the working day. Also, measurements should not be conducted close to the wrist.

Female↗
PubMed2001

Efficacy testing of cosmetic products. A proposal to the European Community by the Danish Environmental Protection Agency, Ministry of Environment and Energy.

BACKGROUND/AIMS: Regulations for cosmetic products primarily address safety of the products that may be used by large populations of healthy consumers. Requirements for documentation of efficacy claims are only fragmentary. This synopsis aims to review and conclude a set of standards that may be acceptable to the European Community, and the cosmetic industry, as a legal standard for efficacy documentation in Europe in the future. METHODS AND RESULTS: Ethical, formal, experimental, statistical and other aspects of efficacy testing are described, including validation, quality control and assurance. The importance of user relevant clinical end points, a controlled randomized trial design and evidence-based cosmetic product documentation, validation of methods, statistical power estimation and proper data handling, reporting and archiving is emphasized. The main principles of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) good clinical practice (GCP) should be followed by the cosmetics industry in a spirit of good documentation standard and scientific soundness, but full GCP is not considered mandatory in the field of cosmetics. Documentation by validated bio-instrumental methods may be acceptable, but efficacy documentation based on information about raw materials, reference to literature and laboratory experiments are only acceptable in exceptional cases. CONCLUSIONS: Principles for efficacy substantiation of cosmetic products in Europe, as described in this synopsis, are officially proposed by the Danish Ministry of Environment and Energy to the European Community as a basis for an amendment to the Cosmetics Directive or otherwise implemented as a European Community regulation.

Clinical Trials as Topic↗
PubMed2001

Ointment is evenly spread on the skin, in contrast to creams and solutions.

BACKGROUND: The efficacy of topical therapy depends on the patient spreading the topical drug in an even layer to give a standard dose. Ointments are believed to be more effective than creams and solutions. OBJECTIVES: To compare the application and spreading of four different pharmaceutical vehicles. METHODS: Twenty-nine healthy volunteers applied a fixed amount (0.1 g) of solution (S), ointment (O), cream (C) and low-viscosity cream (LVC) to the abdominal skin. Area of spread, skin surface lipids (dependent on formulation) and changes in skin surface temperature (cooling due to evaporation of formulation water/alcohol) were measured. RESULTS: Area of spread: O = C = LVC = S. Skin surface lipids: O > C > LVC > S. Difference in skin surface lipids between centre and periphery: O < C = LVC = S. Cooling: O < C = LVC < S. CONCLUSIONS: The four formulations were spread to similar areas. The ointment was spread evenly in the treated area while the other formulations were unevenly spread, with a lower dose in the periphery. Creams and solutions have disadvantages as vehicles, as rapid evaporation of formulation water/alcohol, measured as cooling, influences spread, resulting in an uneven topical dose within the treated area. In contrast, ointment is evenly spread and is thus a more appropriate formulation. Patients should be instructed to apply creams and solutions to multiple sites and to spread them quickly.

Administration, Topical↗
PubMed1999

Effect of barrier perturbation on cutaneous penetration of salicylic acid in hairless rats: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function.

The penetration of topically applied drugs is altered in diseased or barrier-damaged skin. We used microdialysis in the dermis to measure salicylic acid (SA) penetration in hairless rats following application to normal (unmodified) skin (n = 11) or skin with perturbed barrier function from (1) tape-stripping (n = 5), (2) sodium lauryl sulphate (SLS) 2% for 24 h (n = 3) or (3) delipidization by acetone (n = 4). Prior to the experiment, transepidermal water loss (TEWL) and erythema were measured. Two microdialysis probes were inserted into the dermis on the side of the trunk and 5% SA in ethanol was applied in a chamber overlying the probes. Microdialysis sampling was continued for 4 h, followed by measurements of probe depth by ultrasound scanning. SA was detectable in all samples and rapidly increasing up to 130 min. Microdialysates collected between 80 and 200 min showed mean SA concentrations of 3 microg/ml in unmodified and acetone-treated skin, whereas mean SA concentrations were 280 microg/ml in SLS-pretreated skin and 530 microg/ml in tape-stripped skin (P < 0.001). The penetration of SA correlated with barrier perturbation measured by TEWL (P < 0.001) and erythema (P < 0.001). A correlation between dermal probe depth and SA concentration was found in unmodified skin (P = 0.04). Microdialysis sampling in anatomical regions remote from the dosed site excluded the possibility that SA levels measured were due to systemic absorption. Microdialysis sampling of cutaneous penetration was highly reproducible. Impaired barrier function, caused by irritant dermatitis or tape stripping, resulted in an 80- to 170-fold increase in the drug level in the dermis. This dramatic increase in drug penetration could be relevant to humans, in particular to topical treatment of skin diseases and to occupational toxicology.

Absorption↗
PubMed1999

Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function.

We have used microdialysis in the dermis for assessing penetration kinetics of salicylic acid (SA) in healthy volunteers (n = 18), following application on the volar aspect of the left forearm. Penetration was monitored at four locations: in normal (unmodified) skin and in skin with perturbed barrier function from (i) repeated tape stripping (ii) irritant dermatitis from 1 or 2% sodium lauryl sulphate (SLS) for 24 h and (iii) delipidization by acetone. The order of the treatments was randomized according to a latin square design. Epidermal barrier function and skin irritation were assessed in each location using evaporimetry and colorimetry. Transepidermal water loss (TEWL) values confirmed that both mild (acetone), moderate (1% SLS) and severe barrier damage (tape stripping and 2% SLS) had occurred. Microdialysis sampling with two parallel probes in the dermis was performed in each of the four treatment areas for every subject. SA (5% in ethanol) was applied in a chamber glued to the skin overlying the microdialysis probes and sampling was continued for 4 h. SA was detectable in all samples and measurable in all samples from penetration through perturbed skin. Comparing the SA penetration in barrier-perturbed skin with the penetration in unmodified skin in the same subject, the mean SA penetration increase was 2.2-fold in acetone-treated skin (P = 0.012), 46-fold in mild dermatitis and 146- and 157-fold in severe dermatitis and tape stripped skin, respectively (P < 0.001). The penetration of SA significantly correlated with the measurements of barrier perturbation by TEWL (P = 0.01) and erythema (P = 0.02) for each individual. Microdialysis sampling of SA penetration was more sensitive than non-invasive measuring techniques in detecting significant barrier perturbation in acetone-treated skin. A positive dose-response relationship for the percutaneous penetration of SA in response to increasing SLS pretreatment concentrations and thus the degree of irritant dermatitis was found. When analysing data by location on the forearm, a tendency towards an intraregional variation in the reactivity to barrier damage was found, with the most proximal location displaying higher reactivity scores than the most distal location in response to the same barrier perturbation procedures. The penetration of SA was not significantly different between locations. In conclusion, using microdialysis in the dermis to obtain real-time dermal pharmacokinetics in the target organ, this study demonstrates highly increased and differentiated cutaneous penetration of SA in barrier-perturbed skin. The measured drug penetration was demonstrated to correlate with non-invasive quantification of barrier damage.

Administration, Topical↗
PubMed1999

Microdialysis vs. suction blister technique for in vivo sampling of pharmacokinetics in the human dermis.

Our aim was to simultaneously investigate 2 techniques for in vivo sampling of peripheral compartment pharmacokinetics after systemic administration of acetylsalicylic acid. Ten volunteers were given 2 g acetylsalicylic acid orally. Blood samples and dialysates from 4 microdialysis probes inserted in the dermis of the forearm were collected for 5 h and suction blisters were raised 1-3 h after dosing. In microdialysates, both acetylsalicylic acid and the metabolite salicylic acid were measurable in the absence of hydrolysing enzymes. The mean Cmax (maximum concentration) of total, unbound salicylic acid was 9.5 microg/ml in microdialysates, 13.2 microg/ml in suction blister fluid and 56.5 microg/ml in plasma. Mean Tmax (time to Cmax) for salicylic acid was 188 and 161 min in plasma and microdialysates, respectively. The dermis-to-plasma Cmax ratio was 0.16+/-0.04 (mean +/- SD) by microdialysis sampling and 0.25+/-0.09 by the suction blister fluid method. Close correlations (p<0.01) were found between Cmax of salicylic acid in microdialysates and plasma, and between Cmax of salicylic acid in suction blister fluid and plasma. The 2 techniques were in excellent accordance with even closer correlation between maximum concentrations obtained by microdialysis and suction blister fluid sampling (p<0.001). However, comparing the tolerability of the sampling procedure, ease of analysis, and detail in chronology, microdialysis is superior for sampling in vivo pharmacokinetics in the dermis.

Adult↗
PubMed1998

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↗
PubMed1998

Disruption of the vertical calcium gradient in murine epidermis by a potent vitamin D3 analogue, KH 1060.

The hormonal forms of vitamin D3 (1,25-dihydroxyvitamin D3 and synthetic vitamin D3 analogues) are potent regulators of keratinocyte growth and stimulators of keratinocyte differentiation. Recent experiments in vitro on cultured keratinocytes indicate that Ca2+ may be a second messenger mediating the effects related to the induction of keratinocyte differentiation by the hormonal forms of vitamin D3. In this study we employed the technique of ion capture cytochemistry to investigate the effects of a potent vitamin D3 analogue, KH 1060 (20-epi-22-oxa-24 alpha-homo-26,27-dimethyl-1,25-dihydroxyvitamin D3), on the distribution of bound intracellular and extracellular calcium in murine epidermis in vitro. Topical treatment of the skin with KH 1060 (0.4 mmol/l) resulted in the development of epidermal hyperplasia and hyperkeratosis. We observed that epidermis treated with KH 1060 contained fewer calcium deposits in the upper epidermal strata (both intra- and extracellularly) than the control skin. This phenomenon was rapid and occurred after only a single application of KH 1060. Calcium distribution in the basal cell layer was not affected. We propose that observed reduction in the quantity of calcium deposits was caused by the release of sequestered calcium from the intracellular stores and cellular Ca2+ uptake, leading eventually to the increase in the intra-cellular concentration of ionized calcium. The ability of the active vitamin D3 compounds to release Ca2+ may be important for their activity in psoriasis.

Administration, Cutaneous↗
PubMed1998

Cutaneous microdialysis in man: effects of needle insertion trauma and anaesthesia on skin perfusion, erythema and skin thickness.

Cutaneous microdialysis is a method of measuring endogenous and exogenous compounds in the dermal interstitial fluid. The microdialysis probe is inserted in the dermis using a guide cannula. The insertion trauma was studied in dorsal forearm skin in a total of 28 human healthy volunteers. Twenty-four volunteers received local anaesthesia (Xylocain 10 mg/ml) in both forearms and a microdialysis probe was inserted in one of the arms. In 12 volunteers the insertion trauma and the effect of anaesthesia on skin blood flow and erythema were studied by laser Doppler perfusion imaging, Minolta Chromameter CR 200 and Dermaspectrometer. In the other 12 subjects trauma-induced oedema and effects on skin thickness were studied by ultrasound imaging. In addition, a microdialysis probe was inserted without prior anaesthesia in 4 volunteers, and the effects on skin blood flow and erythema were investigated. Significant increases in skin blood flow, erythema and skin thickness were found after insertion of the microdialysis probe. Local anaesthesia prior to the insertion reduced the effects of trauma. Probe depth in dermis did not influence the effects of trauma. At least 90-120 min is required after insertion in order to allow the vascular reaction to needle trauma to return to the baseline range.

Administration, Cutaneous↗
PubMed1998

Cutaneous microdialysis in the rat: insertion trauma studied by ultrasound imaging.

Microdialysis is a method by which compounds can be studied in the extracellular space in skin, in vivo. The microdialysis probe is inserted in the dermis using a guide cannula. It is expected that intradermal oedema associated with insertion trauma as well as the probe depth can influence the results of microdialysis studies. The aim of the present study was to assess the effects of insertion trauma and, additionally, the probe depth by ultrasound. High-frequency (20 MHz) ultrasound is a noninvasive method for measuring the thickness and echostructure of skin. Hairless rats were anaesthetized with either halothane (n = 7) or pentobarbital sodium (n = 6). The insertion of the microdialysis probe resulted in a 38% relative increase in skin thickness. At 120 min the skin thickness had not reached the pre-insertion value. Thus, significant skin thickening, representing traumatic oedema, developed due to insertion of the microdialysis probe in the skin. The microdialysis probe could be inserted reproducibly in the lower dermis.

Administration, Cutaneous↗
PubMed1997

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↗