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Biomedical subjects

E G Weirich

Publications and source records attributed to E G Weirich.

At least 19 recordsLinked to original sources

[Predictive experimental animal test of contact allergenicity. Relevance of the methods of the OECD and EEC guidelines. The organization for Economic Co-operation and Development].

In the first part of this article a historical note is given on the development of predictive contact allergenicity tests in guinea pigs starting with the Draize test, including epidermal methods and at least induction procedures using Freund complete adjuvant as a nonspecific enhancer of immunoreactivity. The tests of the OECD and EEC guidelines are listed and classified according to their predictive sensitivity. It is recommended to test reference allergens by different test methods in one's own laboratory to obtain personal experience with the various methods. Comparisons of the different methods based only on the literature are difficult, because there are so many influences on the performance of sensitization tests and because one is often not sure how the animals were termed positive, i.e. the threshold of a positive erythema score is often not clearly defined. Correlations between test results obtained in guinea pigs and man are presented for the Draize test, the maximization and the optimization test. It is emphasized that guinea pig tests are performed to assess the contact allergenic potential of a compound or formulation, but that the risk assessment is dependent on many other factors and should, therefore, be evaluated separately.

Animals↗

Predictive contact allergenicity influence of the animal strain used.

In order to determine the validity of reported alleged differences in the susceptibility of various strains of guinea pigs to the sensitizing action of known allergens, three unrelated strains of guinea pigs, namely Pirbright White, Hartley and Himalayan spotted strain, were selected. In our investigation, 3 haptens differing in their sensitization potential were used. The results showed that the sensitivity of the 3 given guinea pig strains was comparable. Furthermore, the sensitivity of a given guinea pig strain can only be determined by comparison of the sensitization reaction of several known contact allergens of various sensitizing potential.

Animals↗

[Comparative clinical trial of a new trihalogenated dermatocorticoid (halometasone) versus betamethasone dipropionate].

In a multicenter controlled study carried out in Austria and Switzerland by 8 dermatologists in 208 patients with acute eczematous dermatoses, 0.05% halometasone cream proved to have significantly superior clinical efficacy than 0.05% betamethasone dipropionate cream (P much less than 0.05) showing an equal tolerability. Good to very good results were reported in 93% of the patients treated with halometasone and in 84% of those treated with betamethasone dipropionate creams (Diprosone, Diproderm). General tolerability of both treatments was good. Neither skin atrophy nor any systemic adverse effect, due to the transcutaneous absorption of the corticoids, were observed in this study.

Administration, Topical↗

Evaluation of halometasone ointment in the treatment of paediatric patients with chronic eczematous dermatoses.

Fifty children suffering from non-infected chronic eczematous dermatoses were treated with an ointment containing 0.05% halometasone, a new high potency trihalogenated synthetic corticosteroid. Halometasone ointment does not contain parabens or perfumes. The trial population consisted of patients (under 1 to 16 years old) with non-infected chronic nummular dermatitis, seborrhoeic dermatitis, atopic dermatitis and contact dermatitis. Halometasone ointment yielded very satisfactory therapeutic results and exhibited an excellent tolerability. It produced 'good' or 'very good' results in 82% of the patients and gave an overall cure rate of 76%. The number of patients obtaining an early cure, i.e. in less than 30 days, was thirty-six (72%). An early onset of therapeutic effect, i.e. within 6 days of starting the treatment, was reported in 77.1% of the patients. All the children (including eighteen infants) tolerated halometasone ointment well and no adverse effects, either due to local skin intolerability or the transcutaneous systemic absorption of the corticoid, were observed in this trial, nor were any instances of skin atrophy reported. Cosmetic acceptability and ease of application were considered 'good' in forty-nine (98%) patients.

Administration, Topical↗

The optimization test in the guinea pig in relation to other predictive sensitization methods.

The allergenicity of various compounds was tested by means of the optimization procedure in the guinea-pig. Results with antibiotics, preservatives, fragrance raw materials and miscellaneous contactants are reported. Their relevance is critically discussed in relation to other animal sensitization methods (Draize, Bühler, open epicutaneous and maximization tests). Predictive animal tests are compared with those used in human allergy (Shelanski & Shelanski; maximization test). The importance of animal methods entailing the use of adjuvants is underlined.

Allergens↗

Predictive animal testing for photocontact allergenicity.

The purpose of this investigation was to establish a standardized animal model to predict the photoallergenic potential of new chemical compounds. In a first series of experiments the main factors influencing the induction of photoallergenicity were evaluated (induction concentration, pH of the test solution, pretreatment of the irradiation site with sodium lauryl sulphate, additional use of adjuvant injections and routes of administration). Osram Ultravitalux lamps were utilized for these studies. In a second series of experiments a Xenon 6000 W radiation source was used. Positive results were obtained with well known photosensitizers, as, for instance, the halogenated salicylanilides, as well as with so-called weak photoallergens (e.g. bithionol, sulphanilamide) by stimulating the animals' immune system with Freund's complete adjuvant. The photoallergenic compounds were at the same time tested for their contact allergenic potential in the optimization test. A standard procedure for the predictive photoallergenicity assay in guinea-pigs is proposed.

Adjuvants, Immunologic↗

[Effect of dermatocorticoids on the activity of hepatic tryptophane pyrrolase in the guinea pig (author's transl)].

The enzyme activity of tryptophane pyrrolase in guinea pig liver can be measurably increased--as in other mammalian species--by systemic administration of corticoids, but this effect is short-lived and achieved only with high s.c. doses of, e.g., prednisolone (Ultracorten-H-hydrosoluble). In contradistinction and rather surprisingly the enzyme activity is variably but markedly reduced by high-dosed and protracted epicutaneous application (10 times within 2 weeks) of the well-known dermatocorticoids: hydrocortisone, fluocinolone acetonide, and clobetasol propionate. This reaction must be explained by the capacity of these corticoids to inhibit, after their percutaneous absorption, the functional axis pituitary--adrenal cortex--liver, the stimulatory role of which is mandatory for the endogenous basic activity of hepatic tryptophane pyrrolase.

Administration, Topical↗

Predictive evaluation in animals of the contact allergenic potential of medically important substances. II. Comparison of different methods of cutaneous sensitization with "weak" allergens.

Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives (formalin, ethylenediamine and sorbic acid), drugs (penicillin G, Benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p-phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as 1 in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.

Adjuvants, Immunologic↗

Percutaneous absorption of chlorquinaldol (Sterosan).

The percutaneous absorption of chlorquinaldol from three different preparations for skin treatment (Sterosan-hydrocortison ointment and cream, Sterosan ointment) was evaluated by measuring the cumulative urinary excretion of chlorquinaldol and was compared to that found after an equivalent oral dose. In the blood the concentrations were below the detection limit of the analytical procedure, i.e., smaller than 0.02 microgram/ml. The study was carried out in 3 healthy volunteers using a four-period change-over design. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg chlorquinaldol each, the mean urinary excretion of the drug amounted to 11.1 +/- 6.6, 19.5 +/- 3.5 and 13.0 +/- 2.5% of the applied dose. When the same dose of chlorquinaldol was administered orally, 67.6 +/- 9.5% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations varied between 4.2 and 23.5% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of chlorquinaldol (mean 98.0 +/- 0.1%) was excreted as sulfate (mean 1.3 +/- 0.3%) or unchanged drug (mean 0.8 +/- 0.1%).

Administration, Oral↗

Percutaneous absorption of clioquinol (Vioform).

The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.

Administration, Oral↗

Antimicrobial spectrum of triclosan, a broad-spectrum antimicrobial agent for topical application. II. Comparison with some other antimicrobial agents.

The antimicrobial activity of 5-chloro-2(2,4-dichlorophenoxy) phenol (triclosan, one of the active ingredients of Logamel, Ciba-Geigy) was compared in vitro with that of other antimicrobials exclusively or occasionally used as topical agents in dermatology: hexachlorophene, clioquinol, chlorquinaldol. gentamicin, neomycin, nystatin, econazole, clotrimazole and salicylic acid. Upon determination of the MICs for 53 strains of aerobic and anaerobic bacteria, yeasts and fungi, triclosan was found to display a high degree of activity against most of the test organisms and to have the broadest spectrum of chemotherapeutically significant antimicrobial activity of the substances tested.

Administration, Topical↗