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Biomedical subjects

H Schaefer

Publications and source records attributed to H Schaefer.

At least 37 records · Page 2Linked to original sources
PubMed1988

Use of the chick embryo for pharmacological screening of retinoids.

Retinoic acid and some selected analogs were tested to evaluate their effect on skin morphogenesis and toxicity in the chick embryo. Retinoids dissolved in dimethyl sulfoxide were injected at doses varying from 10 pmol to 10 mumol into the amniotic cavity of 10-day-old chick embryos (n = 20). At 16 days of incubation, the eggs were opened to record the number of dead embryos and the number of embryos presenting club-shaped feathers. A lethal embryotoxic dose (LED50d16) which, at 16 days of incubation, provokes the death of 50% of the embryos and an effective dose (ED50) which induces production of club-shaped feathers in 50% of surviving embryos were then calculated using log-probit analysis. Retinoids could be classified according to their ED50. For example, arotinoid Ro 13-7410 appears approximately 1,000 times more active than all transretinoic acid. However, the analogs which are more active are also more toxic. The assay described in the present study appears to be a simple and useful model for the screening of retinoids.

Animals↗
PubMed1988

Transfollicular percutaneous absorption. Skin model for quantitative studies.

Theoretically percutaneous absorption comprises two components: the transepidermal route and the transappendageal route, so-called 'shunt' diffusion. The relative importance of 'shunt' diffusion was investigated with a model of appendage-free skin. After treatment with 60 degrees C water for exactly 1 min, hairless dorsal rat skin regrows as a continuous epidermis. We present preliminary results of hydrocortisone diffusion in vitro, in appendage-free skin relative to normal skin. With intact skin under our experimental conditions, the steady-state flux and the total diffusion in 24 h were 50-fold larger.

Administration, Cutaneous↗
PubMed1987

Influence of an essential fatty acid deficient diet on absorption of topical hydrocortisone in the rat.

Using a rat dermatosis model, produced by dietary essential fatty acid deficiency (EFAD), which is characterized by histological changes and elevated transepidermal water loss, changes in skin permeability were studied using [14C]-hydrocortisone (HC). Skin, serum and urinary levels of HC were measured, and absorption and excretion of HC in EFAD rats compared with that in control rats on a normal diet. This animal model has demonstrated the importance of the functional integrity of the horny layer in skin penetration.

Administration, Topical↗
PubMed1986

Protection of mitochondrial genetic system against aflatoxin B1 binding in animals resistant to aflatoxicosis.

Administration of a single dose of aflatoxin B1 (AFB1) (6 mg/kg) to Sprague-Dawley rats results in a high level of modification of hepatic mitochondrial DNA (2.1 nmol of AFB1 adducts per mumol DNA-phosphate) and long-term inhibition of mitochondrial transcription and translation activities (N. Bhat et al., Cancer Res., 42: 1876-1880, 1982). Similar doses of AFB1 given to ICR mice and Syrian golden hamsters result in negligible to very low levels (0-06 nmol) of adducts in hepatic mitochondrial DNA. Intact mitochondria from rat liver can metabolize significant amounts of AFB1 (0.29 nmol/mg of protein) without externally added reduced nicotinamide adenine dinucleotide phosphate, and the metabolic activity is stimulated nearly 3-fold by Kreb's cycle intermediates (glutamate and malate), which support intramitochondrial reduced nicotinamide adenine dinucleotide phosphate production. Intact mitochondria from mice and hamsters, on the other hand, metabolize negligible or very low levels of AFB1 (0-0.1 nmol of AFB1 per mg of protein) even when intramitochondrial reduced nicotinamide adenine dinucleotide phosphate production is stimulated by the addition of Kreb's acids. Detergent-solubilized mitoplasts containing less than 1% microsome contamination from all three sources can catalyze the metabolic activation of AFB1 to electrophilic reactive forms as determined in an in vitro DNA binding assay at comparable levels (1.2-2.2 nmol of AFB1 bound per mumol of cytochrome P-450), suggesting that the low levels of AFB1 metabolism by intact mouse and hamster mitochondria and the relative resistance of macromolecular synthesis in these particles to added AFB1 may be due to mitochondrial membrane impermeability. In support of this possibility, AFB1 transported into mouse liver mitochondria through a liposome delivery system causes about 80% inhibition of protein synthesis.

Aflatoxin B1↗
PubMed1986

Characterization of a T-lymphocyte membrane protein involved in T-cell function: its contribution to T-cell recognition or cellular interaction.

A monoclonal antibody (Ab188) specific for guinea-pig T lymphocytes recognizes a membrane heterodimer protein (alpha-chain, MW 43,000; beta-chain, 39,000) and inhibits efficiently the antigen-, mitogen- or alloantigen-induced T-cell proliferation. The role of this protein in T-cell activation was analysed in more detail with emphasis on the recognition or activation event of T cells. Quin 2, an intracellularly trapped calcium indicator, was used to measure calcium influx into T cells. The addition of the mitogen concanavalin A to T cells loaded previously with quin 2 induced an increase in fluorescence, revealing an increase in intracellular free calcium. This calcium increase is considered as one of the primary events in the initiation of T-cell activation and was blocked by Ab188. In contrast, other T-cell specific antibodies that react to a comparable extent with T cells had no effect on calcium increase. This indicates that Ab188 is directed to a protein involved in a very early step of T-cell activation. Alloreactive T-cell lines were established from a secondary mixed leucocyte culture by soft agar cloning. Single T-cell colonies were picked and were propagated by repeated restimulation with allogeneic macrophages differing in MHC-class II antigens. In a chromium release assay, the cytotoxic activity of several strain 13 T-cell lines directed against strain 2 Ia antigens was inhibited by Ab188 to about 50%. Similarly, Ab188 inhibited the cytotoxic activity of a MHC-class I-restricted TNP-specific T-cell line of strain 2 guinea-pigs to about 50%. In contrast, lectin-mediated cytotoxicity of the T-cell lines against murine P815 mastocytoma target cells remained unaffected. These results indicate that Ab188 interferes with the function of a protein contributing to the recognition event in the process of T-cell activation.

Animals↗
PubMed1985

Method for assessment of experimental allergy in guinea pigs adapted to cosmetic ingredients.

2 protocols are presented to predict and assess allergic reactions after application of chemicals or cosmetic products, either raw materials or finished products. The first is an open epidermal induction and challenge, the intensity of the reaction being maximized by injecting Freund's complete adjuvant into the foot pad. The second allows detection of weaker allergens and is a quasi-intradermal induction: both the adjuvant and test substance are injected into the foot pad. In both protocols, the challenge consisted of a single topical application in the lumbar region of 10 microliter of test substance and components, allowing study of cross-sensitization, the large surface available permitting 6 different contacts.

Administration, Topical↗
PubMed1985

The in vivo fate of topically applied dithranol in the skin of the hairless rat. A comparison of continuous and short contact application.

The fate in vivo of topically applied 1,8-dihydroxy-9-anthrone (dithranol, anthralin) was investigated in the skin of the hairless rat, using a specially designed drug delivery system (film). The film was applied on intact skin as well as on skin with an impaired barrier function (stripped skin). The distribution of the drug was examined either after continuous application or at selected times after short contact periods. The exposed skin was extracted with diisopropylether and free dithranol, its dimer and quinone assayed by quantitative HPLC analysis. The incorporation of trace amounts of 3H-dithranol and 14C-dithranol in the vehicle made it possible to quantify the fraction of penetrated drug which was insoluble in ether. With continuous application to intact skin (up to 24 h), extractable dithranol rapidly reached a plateau level (15 min) and was concentrated in the stratum corneum. Substantial dimer formation occurred in both normal and stripped skin. Ether insoluble material rapidly predominated over soluble material, especially when the stratum corneum was absent. However, on short contact application (0.5-1 h), ether soluble material (dithranol in the stratum corneum) was quantitatively predominant in the intact skin. Removal of the vehicle after a short contact time resulted in the disappearance of dithranol from the skin (normal and stripped). In intact skin, the drug was converted into ether insoluble material. In the stripped skin, this insoluble fraction remained constant over the duration of the experiment (24 h).

Administration, Topical↗
PubMed1979

Microcalorimetric investigations of the metabolism of isolated human epidermis.

Microcalorimetry was used for the evaluation of metabolic and enzyme activity in human epidermis. The endogenous metabolism with a heat production Q = -2 muW/mg wet weight could be stimulated to Q = -12 muW/mg by adding glucose to the buffer. To test the enzyme activity, hydrogenation of pyruvate to lactate by lactate dehydrogenase (LDH) was chosen as an essential step of anaerobic glycolysis. The LDH activity of epidermis slices amounted to 22 mU/mg epidermis. The microcalorimetric method is discussed as a test procedure for specimens of healthy and diseased skin and for cell cultures.

Calorimetry↗
PubMed1979

The quantitative distribution of percutaneously applied caffeine in the human skin.

The distribution coefficient of caffeine (water/n-Octanol) and the estimation of caffeine in urine after local application indicate to a high permeation rate of caffeine through the skin. This could be confirmed by using different vehicles in vivo and in vitro. 14C labeled caffeine penetrates rapidly the epidermis and corium. The maximum of absorption is reached at 100 min after local application in vivo. In vitro by absence of the transport possibilities of blood and lymph vessels, the concentration at 1,000 min after local application is 450 X higher than in vivo. Therefore, after 1,000 min in vivo the concentration of caffeine in the different skin layers is very low.

Administration, Topical↗
PubMed1979

Contraception via topical application? - A review.

The skin, generally speaking, is not an absorption organ but one of its major functions is the protection of the body against the entrance of foreign material. Under certain circumstances, however, drugs can be introduced into the skin and thereby into the body as can be seen in the topical treatment of skin diseases. Though percutaneous pharmacokinetics of steroids seem appropriate for contraception, the variability of the absorption process appears to be too high for this purpose.

Absorption↗
PubMed1979

Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro.

Binding of the two photosensitizers, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), to serum proteins and to epidermis was measured. 8-MOP binds to serum proteins with an apparent dissociation constant (Kd) of 4 x 10(-5) M. Under conditions of oral therapy, serum concentrations of the photosensitizer 2 h after administration are usually in the range of 100-1000 ng per ml serum. In this concentration range, 75-80% of the drug was found to be reversibly bound to serum proteins. 5-MOP shows a higher binding affinity to serum proteins and 98-99% of the drug is protein bound. The binding of both psoralen derivatives appears to take place mainly to serum albumin. 5-MOP and 8-MOP bind to different and non-interacting sites on serum proteins and the binding of the one has no effect on the binding of the other methoxypsoralen. Both photosensitizers bind reversibly to human epidermis. 8-MOP concentration in the epidermis is increased by ten to twenty fold compared with the equilibrium buffer. 5-MOP shows a higher binding affinity, resulting in a higher tissue concentration of the photosensitizer. As in serum, the two drugs appear to be bound in the epidermis to independent and non-interacting sites. No binding competition was found between the two methoxypsoralens and hydrocortisone, fluocinonide and acetyl salicylic acid, either in serum or in epidermis, using up to 1000 fold higher concentrations as compared with those of 5-MOP and 8-MOP.

Binding, Competitive↗