Non-immunologic contact urticaria. Animal tests and their relevance.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
A Lahti
Publications and source records attributed to A Lahti.
Contact dermatitis. A review.
In recent years, there has been a dramatic rise in our understanding of contact dermatitis. This paper is a review of our knowledge of the mechanisms involved in contact dermatitis and related phenomena, the investigation of these events and the emergence of significant new allergens during the last 5 years.
Allergens↗
Acetylsalicylic acid inhibits non-immunologic contact urticaria.
To investigate the mechanisms of non-immunologic contact urticaria (NICU), the effects of 1g + 1g of acetylsalicylic acid (ASA) on contact reactions to methyl nicotinate, diethyl fumarate, benzoic acid, cinnamic acid, cinnamic aldehyde and dimethyl sulfoxide were studied in 21 test subjects. Erythema and edema reactions were observed visually, and the changes in the skin blood flow were monitored using laser-Doppler flowmetry. ASA had a significant inhibitory effect on erythema from all 6 agents and also on edema from all substances except dimethyl sulfoxide. The mechanism of the effect may be a result of the inhibitory influence of ASA on prostaglandin bioformation. Thus, to avoid false negative test results, non-steroidal anti-inflammatory drugs should not be used during NICU tests.
Acrolein↗
Terfenadine does not inhibit non-immunologic contact urticaria.
To investigate the mechanisms of non-immunologic contact urticaria (NICU), the effect of 120 mg of terfenadine (H1-antagonist) on contact reactions to methyl nicotinate, diethyl fumarate, benzoic acid, cinnamic acid, cinnamic aldehyde and dimethyl sulfoxide was studied in 20 subjects. Erythema and edema were observed visually, and the changes in the skin blood flow were monitored with laser-Doppler flowmetry. Terfenadine did not have any significant inhibitory effect on erythema or edema from 6 contact urticariants tested, but it inhibited erythema and edema of prick test reactions to histamine. Non-specific histamine release from mast cells does not seem to be the mechanism of NICU from these substances.
Benzhydryl Compounds↗
Pharmacological studies on nonimmunologic contact urticaria in guinea pigs.
In the present study we examined the effects of chlorpheniramine and ranitidine, indomethacin, BW755C (an inhibitor of cyclo-oxygenase and lipo-oxygenase enzymes of arachidonic acid metabolism), dexamethasone, and capsaicin on nonimmunologic contact urticaria (NICU) induced in the guinea pig ear by benzoic, acid cinnamic acid, cinnamic aldehyde, methyl nicotinate, diethyl fumarate, or dimethyl sulfoxide. The intensity of edema in the urticarial reaction was quantified by measuring the ear thickness. Antihistamines inhibited reactions to intradermal histamine but not to agents causing NICU. Indomethacin and dexamethasone inhibited reactions to cinnamic acid and cinnamic aldehyde but not to other NICU agents. BW755C and capsaicin had no effect on reactions to any of the NICU agents. Mast cell degranulation during the reaction was not seen in histologic sections. Histamine and capsaicin-sensitive nerves did not seem to be essential for the development of NICU in the guinea pig ear. The details of the inhibitory effects of indomethacin and dexamethasone are not clear, but it seems probable that more than one mechanism is involved in NICU due to different agents.
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
The carcinogenic properties of topical PUVA. A lifelong study in mice.
The tumorigenic properties of topical methoxsalen (8-MOP) and trioxsalen (TMP) plus ultraviolet light A (UVA) were studied in NMRI female mice. The animals were treated three times weekly for 9 months, and followed up for 18 months. Acetonic solutions of TMP (0.1 mg in 0.2 ml) and 8-MOP (0.6 mg in 0.2 ml) were applied to the shaved back skin of the mice and irradiated with UVA. The doses needed to elicit equivalent phototoxic effects were 0.29 J/cm2 in the TMP group and 1.09 J/cm2 in the 8-MOP group. Papillomas, keratoacanthomas, and squamous cell carcinomas developed in the 8-MOP group only, and the first tumor was seen at 10 months after the beginning of the study. The results suggest that the carcinogenicity of these two modes of photochemotherapy may differ.
Animals↗
Dermal prostacyclin, thromboxane A2 and prostaglandin F2 alpha in climacteric women: effect of oestrogen replacement therapy.
The involvement of dermal prostanoids in menopausal flushing was studied in 8 women suffering from climacteric hot flushes and in 10 asymptomatic control subjects by inducing suction blisters on abdominal skin and assaying blister fluids for 6-keto-PGF1 alpha, a metabolite of the vasodilative prostacyclin (PGI2), thromboxane B2 (TxB2), a metabolite of the vasoconstrictive thromboxane A2 (TxA2), and 13,14-dihydro-15-keto-PGF2 alpha (M-PGF2 alpha), a metabolite of prostaglandin F2A (PGF2A). No marked differences were observed in the levels of these prostanoids in the two study groups. The women experiencing flushes then received conjugated oestrogens for 3 mth to abolish vascular instabilities. This decreased the blister fluid concentration of M-PGF2 alpha from 1720 +/- 476 pg/ml (mean +/- SE) to 1490 +/- pg/ml (P less than 0.05), but had no effect on the dermal levels of 6-keto-PGF1 alpha or TxB2. It was concluded that although certain dermal prostanoids may be affected by oestrogen treatment they are not of primary significance as regards menopausal flushing.
6-Ketoprostaglandin F1 alpha↗
Peroral challenge tests with food additives in urticaria and atopic dermatitis.
Double-blind, placebo controlled challenge tests with benzoic acid butylhydroxytoluene, butylhydroxyanisole, beta-carotene, beta-8-apo-carotenal, and sodium metabisulfite were made in 44 cases of chronic urticaria, 91 cases of atopic dermatitis, and 123 cases of contact dermatitis, as a comparison group. Positive reactions were seen in four patients, two of whom had urticaria, one atopic dermatitis, and one contact dermatitis. Two of these reactions were caused by the placebo, one in a patient with urticaria and the other in a contact dermatitis patient. For one patient who reacted to the placebo and one who reacted to benzoic acid, the challenges were repeated with positive results in both instances. In nine patients, equivocal test results were produced with all the active substances and the placebo, but in all nine cases, retesting 4 days later produced negative results. This suggests that common food additives are seldom if ever of significance as precipitating factors in chronic urticaria or atopic dermatitis.
Adolescent↗
Contact urticaria and respiratory symptoms from tulips and lilies.
Explore the source record for details and available documents.
Adult↗
Species specificity of nonimmunologic contact urticaria: guinea pig, rat, and mouse.
In order to find the most suitable animal species for studies on nonimmunologic contact urticaria (NICU), human NICU agents: 20% benzoic acid (BA), 10% sorbic acid (SA), 15% cinnamic acid (CA), 20% cinnamic aldehyde (CAL), 1.0% diethyl fumarate (DEF), 0.2% methyl nicotinate (MN), all in absolute ethyl alcohol, and 100% dimethyl sulfoxide (DMSO) were each applied to the earlobes of guinea pigs, rats, and mice. Guinea pig ear reacted with swelling to all agents tested. The mean maximal increase in thickness of the guinea pig ear, measured with a micrometer, was 114 +/- 46%. No response to BA, SA, CA, DEF, or MN was noted in the rat or mouse ear. However, DMSO and CAL caused significant ear swelling both in the mouse and the rat. Thus, the guinea pig ear is more sensitive to a variety of human NICU agents than is rat or mouse ear. The striking differences in species reactivity to NICU agents suggest the possibility that there are several mechanisms (mediators) involved in reactions to different substances. The guinea pig ear swelling test remains the best quantitative animal method available for screening human NICU agents.
Animals↗
Long refractory period after one application of nonimmunologic contact urticaria agents to the guinea pig ear.
The decrease in the swelling capacity and the length of the refractory period after nonimmunologic contact urticaria produced by one application of six human nonimmunologic contact urticaria agents was studied with the use of the guinea pig ear test. On retesting 1 day later, all substances (benzoic acid, cinnamic acid, cinnamic aldehyde, diethyl fumarate, methyl nicotinate, and dimethyl sulfoxide) showed reactions decreased by at least 50%. This decrease was most marked with cinnamic aldehyde (91% decrease), cinnamic acid (88%), and benzoic acid (86%). The tachyphylaxis was not specific to the substance producing it; reactivity to other contact urticaria agents decreased as well. The refractory period was 4 days after methyl nicotinate, 8 days after diethyl fumarate and cinnamic aldehyde, and 16 days after the other agents. These results suggest the following practical application: there is a need for (1) appropriate scheduling in the reuse of animals for testing for nonimmunologic contact urticaria and (2) an awareness of possible false-negative results in human tests for this form of urticaria because of tachyphylaxis.
Acrolein↗
Contact urticaria from diethyl fumarate.
The contact urticariagenic properties of diethyl fumarate were studied using the guinea pig ear swelling assay and by open application on the human upper back skin. Diethyl fumarate caused non-immunologic contact urticaria in both human and guinea pig skin, and the reactions exhibited similar dose dependency and timing of maximal response.
Adult↗
Carcinoma of the lip. A retrospective study of 70 patients.
From 1966 to 1978, 70 patients with carcinoma of the lip were treated at the Division of Plastic Surgery, University Central Hospital, Helsinki. The lip tumour was a squamous cell carcinoma in 64 patients, and a basal cell carcinoma in 6 patients. Of these 70 patients, 24 had radiotherapy as the primary mode of therapy and 46 patients had been treated initially by surgery. The results of surgery were generally good. However, in the group of "simple wedge excision" and in patients who had had radiotherapy as the primary treatment there was a higher incidence of recurrences. In the former group the recurrences were considered to be due to a too narrow angle of excision. We recommend surgery as the primary method of treatment because of the availability of histologically accurate tumour margin assessment, the short rehabilitation period and the good functional results achieved.
Aged↗
An animal model for nonimmunologic contact urticaria.
The suitability of the guinea pig for studies on nonimmunologic contact urticaria (NICU) was investigated. Groups of five, female Hartley guinea pigs were challenged by applying 50 microliters of various concentrations of human NICU agents, benzoic acid (BA), sorbic acid (SA), cinnamic acid (CA), cinnamaldehyde (CAL), methyl nicotinate (MN) and dimethyl sulfoxide (DMSO), in absolute ethyl alcohol to both sides of the earlobe. The thickness of the ear (0.85 +/- 0.11 mm, means +/- SD, 100 animals) was measured with a string micrometer before application and at 5- to 30-min intervals thereafter. Maximal increase in ear thickness was produced within 30 to 40 min by 20% BA (0.70 +/- 0.09 mm), 10% SA (0.30 +/- 0.05 mm), 15% CA (0.58 +/- 0.12 mm), 5.0% CAL (0.37 +/- 0.09 mm), 0.2% MN (0.80 +/- 0.03 mm), and 100% DMSO (0.74 +/- 0.11 mm). All responses were dose dependent. The histology of the maximal reactions showed dermal edema, and intra- and perivascular infiltrate of heterophils (neutrophils in man), eosinophils, and some lymphocytes. DMSO also caused vacuolization of the epidermal cells. CAL, MN, and DMSO, applied to different parts of the guinea pig body, produced only erythema most frequently on the upper back, but BA, SA, and CA did not cause any reactions. The guinea pig ear-swelling test provides a quantitative animal model to screen human NICU agents.
Animals↗
Early equatorial cataracts in workers exposed to trinitrotoluene.
Twelve workers (nine men and three women with a mean age of 39.5 +/- 8.9 years) with occupational exposure to trinitrotoluene had a mean duration of exposure of 6.8 +/- 4.7 years. The general physical findings were minimal, but ophthalmologic examinations showed bilateral peripheral cataracts in six of the 12 workers. Cataracts were visible only with maximal mydriasis and were continuous or annular opacities at the equator. The cataracts did not interfere with visual acuity or visual fields. Only one worker with and one without cataracts had increased serum alanine aminotransferase and bilirubin levels, possibly associated with trinitrotoluene exposure.
Adult↗
Prostaglandins in contact urticaria induced by benzoic acid.
To study the role played by prostaglandins (PGs) in contact urticaria, concentrations of 13,14-dihydro-15-keto-PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2, the stable metabolites of PGF2 alpha, prostacycline and thromboxane A2 were measured by radio-immunoassay of the fluid taken from suction blisters in 11 patients. The blisters were raised on contact urticarial reactions induced by benzoic acid. The effect of peroral indomethacin on contact urticaria from benzoic acid was studied in a further 14 dermatological patients. The levels of these prostanoids in the blister fluid of urticarial skin did not differ from those derived from control blisters raised on apparently normal skin. Premedication with indomethacin, 50 mg t.i.d., completely prevented contact urticarial reactions to benzoic acid in all patients.
Adolescent↗
Topical immunotherapy with tuberculin jelly for common warts.
Explore the source record for details and available documents.
Administration, Topical↗
Is benzoic acid really harmful in cases of atopy and urticaria?
Explore the source record for details and available documents.
Benzoates↗