The allergen bank: the idea behind it and the preliminary results with it.
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Allergens↗
Biomedical subjects
K E Andersen
Publications and source records attributed to K E Andersen.
The guinea pig maximization test--with a multiple dose design.
The guinea pig maximization test (GPMT) is usually performed with one moderately irritant induction dose of the allergen and gives a qualitative assessment-hazard identification-of the allergenicity of the chemical. We refined the GPMT by applying a multiple dose design and used 30 guinea pigs in a test divided into a control group and 5 test groups of 5 animals. Each group was treated with different induction concentrations of the allergens: formaldehyde, cinnamic aldehyde, propyl paraben, lidocaine, mercaptobenzothiazole or chlormethylisothiazolinone/methylisothiazolinone. The test results were analysed using a logistic multidose response model. The precision of the results depends only on the total number of animals, the dose design and the response pattern. The maximal sensitization rate for a chemical was determined, and the intracutaneous induction concentration that sensitized 50% of the animals (EC50) (or another percentage) was estimated. Further studies are needed to prove the validity of this idea. However, improvements in protocols for the GPMT are needed to reduce interlaboratory variability in results and to reduce the number of animals used for allergenicity tests.
Acrolein↗
Quantitative autoradiographic characterization of the binding of [3H]tiagabine (NNC 05-328) to the GABA uptake carrier.
The kinetic properties and regional distribution of [3H]tiagabine ([3,4-3H]N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid) binding to the central GABA uptake carrier was examined in the rat brain using quantitative receptor autoradiography. In slide mounted sections of frontal cortex, the binding of [3H]tiagabine was saturable, reversible and sodium dependent. The kinetics of association and dissociation of [3H]tiagabine were monophasic, and Scatchard transformation of saturation isotherms resulted in a linear plot with a Kd = 58 +/- 7 nM and a Bmax = 58.9 +/- 0.9 pmol/mg protein. The autoradiographic distribution of [3H]tiagabine binding sites in rat brain was heterogeneously distributed. The highest density of [3H]tiagabine binding sites was present in the cerebral cortex, mammillary body, globus pallidus, substantia nigra pars reticulata, hippocampus, dorsal raphé, superior colliculus (outer layer), and cerebellum. The distribution of GABA uptake sites, as measured by [3H]tiagabine binding, in the rat brain is highly consistent with the organization of GABAergic terminals and cell bodies. The present investigation characterized the use of [3H]tiagabine as a novel radioligand for the GABA uptake carrier using quantitative receptor autoradiography. [3H]Tiagabine has several major advantages over the currently utilized radioligand for the GABA uptake carrier [3H]nipecotic acid, in that [3H]tiagabine has an increased affinity, specificity, and is not transported intracellularly via the GABA uptake carrier. These data suggest that [3H]tiagabine represents a novel and highly useful ligand for studying the GABA uptake carrier using quantitative receptor autoradiography.
Animals↗
Contact allergy to 2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert-butylphenol, components of a phenolic resin used in marking pens.
2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert-butylphenol were identified as contact allergens in a phenolic resin used as a tackifier in the ink of a marking pen, which, after being used directly on the skin, caused an acute contact dermatitis on the hand of a 13-year-old boy. The patient also reacted to 4-tert-butylphenol-formaldehyde resin (BPF resin) 1% pet. included in the European standard series.
Acute Disease↗
How to do sensitization tests in guinea pigs.
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Animals↗
Nickel patch test reactivity and the menstrual cycle.
Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation to the menstrual cycle. Twenty women with regular periods were tested on day 7-10 and on day 20-24. Ten nickel patch tests with different concentrations were applied using the TRUE test assay, and the threshold concentration of nickel sulphate eliciting an erythematous reaction was determined. Half of the women were tested first on day 7-10 and the other half first on day 20-24. There was no difference in the degree of patch test reactivity, when the results from day 7-10 and day 20-24 were compared (p > 0.4). However, when we compared the patch test results from the first and second test procedure, we found an increased nickel sensitivity at the second patch test (0.02 < p < 0.05), suggesting a booster effect from the first patch test procedure. In conclusion, we could not demonstrate an increased sensitivity to nickel sulphate patch tests premenstrually in 20 nickel allergic women, but we found that elicitation of positive patch tests led to an increased skin reactivity towards the same allergen, when the patients were retested weeks later.
Adolescent↗
The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate.
A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptosomes was determined for each compound. It was found that the most potent examples are those having a substituent in an "ortho" position in one or both aromatic/heteroaromatic groups. The majority of the compounds described are structurally related to tiagabine, (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3- piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized.
Animals↗
[Incidence of hand eczema after surgical washing and use of surgical gloves].
Contact dermatitis caused by surgical gloves is well known. Contact urticaria and anaphylactoid reactions among hospital personnel and patients following contact with latex gloves and glove dusting powder have previously been reported. A suspected increased frequency of hand eczema among personnel using detergents and surgical gloves in operating units initiated the present study. A questionnaire survey was performed in order to examine the frequency and degree of hand eczema among 332 surgeons and nurses working at the surgical units of Odense University Hospital during the period 1.6.-1.9.1989. A total of 242 persons (72%) answered the questionnaire. One hundred and fourteen persons (47%) claimed to develop skin discomfort or hand eczema following the washing procedure or use of surgical gloves. Among the personnel with skin problems 60% had spontaneously changed to another detergent/glove-product with subsequent clearing of the symptoms in 75% of the cases. Dermatological examination and patch tests were performed with European Standard series, gloves, rubber chemicals and selected soap components in 53 persons. Hand eczema was found in 16 persons (7%). Positive patch test reactions to latex gloves were found in four persons and only one person reacted to the rubber accelerators known to be present in the gloves according to the manufacturers' information. Among 26 persons with skin-discomfort and immediate symptoms, ten were prick tested with the standard battery of inhalant allergens, corn starch surgical glove powder, and extract of surgical gloves. Three persons reacted to glove extract, none reacted to glove powder.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Dose-response testing with nickel sulphate using the TRUE test in nickel-sensitive individuals. Multiple nickel sulphate patch-test reactions do not cause an 'angry back'.
The aim of this study was to employ the TRUE test assay to confirm the presence or absence of the 'angry back' phenomenon, i.e. that a strong positive patch-test reaction heightens adjacent patch-test response. In addition, we wished to establish the dose-response relationship for nickel sulphate patch tests among nickel-sensitive patients. Seventy-two nickel-sensitive patients, 36 in Odense and 36 in Stockholm, were tested with a 10-step nickel sulphate dilution series (TRUE test) and two placebo patches. The position of the patches was rotated, to provide a balanced spatial distribution of the different concentrations. Readings were performed blind. The results were analysed by means of polynomial multiple-regression methods and a logistic dose-response model. Half the patients (38/72) had a threshold patch-test concentration for nickel sulphate in the range of 3-0.3 microgram/cm2. The 'angry back' phenomenon was not apparent in this study, as the spill-over effect was not statistically significant. Strong reactions to high concentrations of nickel sulphate did not enhance the response to adjacent lower concentrations of nickel sulphate.
Dermatitis, Allergic Contact↗
Should patch testing be restricted to dermatologists only?
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Dermatitis, Allergic Contact↗
Carvone: an overlooked contact allergen cross-reacting with sesquiterpene lactones?
The terpene l-carvone is one of the main constituents of spearmint oil. The sensitizing potential of l-carvone has been considered low, but it has occasionally caused contact allergy in users of spearmint toothpaste and chewing gum. l-Carvone is also an oxidation product of d-limonene that occurs in solvents used increasingly in industry. We included l-carvone 5% pet. in the standard patch test series. In the 1st year, 541 patients were tested and 15 (2.77%) had positive, and 12 doubtful positive (?+) reactions to l-carvone. The strongest reactions were observed in 9 patients with concomitant Compositae sensitivity. The key clinical features and other contact allergies of the patients are presented. When re-testing with l-carvone in the same or lower concentrations, only 2 out of 8 patients had positive reactions. Possible reasons for this discrepancy are discussed in terms of cross-reactions, concomitant sensitization, excited skin syndrome, irritancy and facilitated immunological response.
Adult↗
Compositae dermatitis in a Danish dermatology department in 1 year (II). Clinical features in patients with Compositae contact allergy.
During our first year of routine testing with Compositae allergens and extracts, contact allergy to Compositae was frequently found in eczema patients (4.5%), especially in middle-aged or elderly persons. Based on clinical patterns, patch test reactions and the long-term course of the disease, 4 groups of patients were recognized: (a) a small group with localized eczema; (b) another with classic Compositae dermatitis of exposed skin; (c) a 3rd group, the largest, with localized eczema that suddenly one summer turned into a widespread dermatitis; (d) a 4th group with a vesicular hand eczema and more-or-less widespread dermatitis with seasonal variation from the beginning. 65% of the patients had vesicular hand eczema at some time, partly reflecting the frequency of atopy (25%) and metal allergy (44%). 75% of the patients had contact allergy to > or = 1 compounds besides Compositae. Thus, Compositae allergy may be primary, e.g., in young patients with occupational plant contact, or secondary to other contact allergies, perhaps as a result of increased individual susceptibility. The clinical patterns in the latter patients were most often a widespread dermatitis with summer exacerbation. The variability in the clinical picture makes routine patch testing with Compositae allergens recommendable.
Adult↗
Compositae dermatitis in a Danish dermatology department in one year (I). Results of routine patch testing with the sesquiterpene lactone mix supplemented with aimed patch testing with extracts and sesquiterpene lactones of Compositae plants.
To investigate the frequency of Compositae sensitivity, the recently-developed sesquiterpene lactone mix (SL mix) was included in the standard patch test series. Patients with positive reactions to this or patients suspected of having a Compositae allergy were supplementarily tested with a Compositae mix, consisting of ether extracts of 5 European Compositae plants. In the first year, 686 patients were tested with the SL mix and 79 with the Compositae mix. A total of 31 Compositae-sensitive patients (4.5%) were found. The frequency of positive reactions to either of the mixes was equal, but only 17 of 30 patients tested were positive to both mixes. Testing with the individual ingredients of the Compositae mix showed frequent positive patch test reactions to feverfew, followed in order by chamomile, tansy, yarrow and arnica. The reason for this distribution is discussed and the results of standard, photo- and other plant patch tests are presented. The only partial overlap between positive reactions to the mixes emphasizes the necessity of supplementary testing in patients suspected of Compositae allergy, as well as the lack of a reliable single screening agent. Since no cases of active sensitization or irritant reactions were seen, both the SL mix and the Compositae mix may be considered suitable for routine screening of Compositae allergy.
Adult↗
NNC-711, a novel potent and selective gamma-aminobutyric acid uptake inhibitor: pharmacological characterization.
NNC-711 (1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride) is a novel, potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor. NNC-711 inhibited synaptosomal (IC50 = 47 nM), neuronal (IC50 = 1238 nM) and glial (IC50 = 636 nM) GABA uptake in vitro NNC-711 lacked affinity for other neurotransmitter receptor binding sites, uptake sites and ion channels examined in vitro. In vivo, NNC-711 was a potent anticonvulsant compound against rodent seizures induced by methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (ED50 (clonic) = 1.2 mg/kg i.p.), pentylenetetrazole (PTZ) (ED50 (tonic) = 0.72 mg/kg i.p., mouse; and ED50 (tonic) = 1.7 mg/kg, rat), or audiogenic (ED50 (clonic and tonic) = 0.23 mg/kg i.p.). At higher doses NNC-711 produced behavioral side effects characterized by inhibition of traction (ED50 = 23 mg/kg i.p.), rotarod (ED50 = 10 mg/kg i.p.) and exploratory locomotor activity (ED50 = 45 mg/kg i.p.) in the mouse. Following acute (3-h) in vivo pretreatment with NNC-711, behavioral tolerance developed to its motor impairing side effects (inhibition of traction, rotarod or exploratory locomotor activity) without corresponding tolerance to the anticonvulsant effects. These data suggest that NNC-711 will be useful for future in vitro and in vivo experiments to elucidate the role of the GABA uptake carrier in the central nervous system.
Animals↗
[Atopic dermatitis--many causes and therapeutic possibilities].
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Dermatitis, Atopic↗
In vivo labeling of the central GABA uptake carrier with 3H-Tiagabine.
The in vivo binding of 3H-Tiagabine to the central GABA uptake carrier in mouse brain was characterized. 3H-Tiagabine in vivo bound to a single class of binding sites with a Kd = 72.5 nM and a Bmax = 640 pmol/g tissue. 3H-Tiagabine binding in vivo was regionally distributed within the CNS, and showed a good correlation with 3H-Tiagabine binding in vitro. Pharmacological characterization of 3H-Tiagabine binding in vivo revealed a binding site exhibiting specificity for GABA uptake inhibitors. Experiments examining the in vivo receptor occupancy of the GABA uptake carrier for a series of GABA uptake inhibitors revealed that 20-30% of the GABA uptake sites were occupied at the ED50 for inhibiting DMCM-induced clonic convulsions, while a 50-62% receptor occupancy in vivo was needed to inhibit rotarod performance. These data suggest that 3H-Tiagabine in vivo binding may be a useful method for assessing GABA uptake inhibitor penetration into the CNS, and may be a useful tool for studying the physiological regulation of the GABA uptake carrier.
Animals↗