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Biomedical subjects

H Schaefer

Publications and source records attributed to H Schaefer.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Skin metabolism].

The skin, one of the organs which accounts for the largest proportion of total body weight, was long viewed only as a passive physical barrier between the body from the environment. Over the last ten years, many studies have demonstrated significant metabolic processes in the skin, due in particular to the effects of enzymes which are located mainly in the epidermis. This skin metabolism has a marked effect on percutaneous penetration of xenobiotics. In this review, enzyme activities detected in the skin and their location in the various skin layers are discussed, as well as the different in vitro and in vivo models for studying skin metabolism. Pharmacologic or toxic effects of active ingredients or their metabolites may be associated with the nature and magnitude of transformations of xenobiotics in the skin (first pass effect). The impact of skin metabolism on the effects of topically applied drugs and the factors capable of modulating skin biotransformations are discussed. The main difficulties faced by skin metabolism studies stem from the relatively complex structure of skin and in the low levels of enzymatic activities.

Cytochrome P-450 Enzyme System↗
PubMed1991

Follicles play an important role in percutaneous absorption.

The relative importance of stratum corneum and follicles in percutaneous absorption is not fully understood. In order to quantitatively investigate the importance of the transappendageal route, we have previously developed a model of skin without follicles regrown dorsally on the hairless rat. Percutaneous absorption was compared, using a diffusion cell, in appendage-free skin relative to normal skin, and a predominant role of follicles for in vitro diffusion of [3H]hydrocortisone was noted. Results presented here of in vitro diffusion of tritiated hydrocortisone, niflumic acid, caffeine, and p-aminobenzoic acid, applied in acetone, confirm that appendageal diffusion is the major pathway in hairless rat skin. In the absence of follicles, the steady-state flux and the amounts diffusing in 24 or 48 h are 2-4 times lower than in normal skin. These results were confirmed in a second model in which diffusion of [3H]hydrocortisone was studied on skin samples taken one day after birth, at which time rat skin is still devoid of follicles, relative to five-day postnatal skin samples, in which follicles are fully developed. The steady-state flux and the total diffusion in 24 h were fivefold lower in follicle-free skin. These results support the view that follicles may have a far greater importance in percutaneous absorption than is generally assumed.

4-Aminobenzoic Acid↗
PubMed1991

Quantification of skin-colour changes induced by topical corticosteroid preparations using the Minolta Chroma Meter.

The Minolta tri-stimulus colorimeter CR-200 was used to quantify the blanching effect of topical corticosteroids in a non-occluded vasoconstriction test. To investigate the influence of time on variations in colorimetric parameters, an initial series of measurements was performed on Day 1 on six predetermined sites on the ventral surface of the forearm of six healthy volunteers every 2 h over a 12-h period. The colorimetric values were shown to be site related but hourly variations occurred with similar profiles for all the sites. On Day 2, four topical corticosteroid creams, representative of their potency groups, as well as a base were applied in a randomized double-blind manner on five of the predetermined sites. Visual gradings and colorimetric measurements were carried out every 2 h over the following 12-h diurnal period and were continued on Day 3. The colorimetric parameters L* (luminance) and a* (colour hue ranging from green(-) to red(+] gave a rank order correlated to corticosteroid potency that showed superior discrimination compared to simple visual grading. In this study, L* was more discriminative parameter than a*. The Minolta Chroma Meter CR-200 appears to be a simple and accurate device for objectively measuring the blanching effects of topical corticosteroids.

Administration, Topical↗
PubMed1991

Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris.

CD 271, a naphthoic acid, is a powerful modulator of epidermal differentiation. This double-blind, randomized study compared the efficacy and safety of two concentrations (0.03% w/w and 0.1% w/w) of CD 271 alcoholic gel, with 0.025% w/w tretinoin gel in 72 male patients with acne vulgaris over a period of 12 weeks. Efficacy was measured by counting facial inflammatory and non-inflammatory lesions and by grading the severity of the acne at each visit. Skin tolerance was assessed with subjective symptoms, such as burning and pruritus, as well as clinical assessment of erythema, dryness and scaling on the treated areas. The alcoholic 0.1% CD 271 gel was as effective as 0.025% tretinoin gel in reducing total comedone counts (83% reduction for both products after 12 weeks' treatment). The reduction in the number of inflammatory lesions and the total number of acne lesions were significantly greater with 0.1% CD 271 gel than with tretinoin gel (69% and 79% for 0.1% CD 271, 50% and 73% for tretinoin gel, respectively, P less than 0.05). All three treatments were well tolerated and there were no changes in any major blood parameters. No CD 271 could be detected in blood plasma at the end of the study (detection limit = 1 ng/ml).

Acne Vulgaris↗
PubMed1991

Physiology of the vellus hair follicle: hair growth and sebum excretion.

The growth of vellus hair and the secretion of sebum from vellus hair follicles were measured on the forehead, cheek, chest, shoulder and back of healthy men and women aged 15-30 years. Hair growth was assessed by computerized image-analysis of photographs and sebum excretion by the use of Sebutape followed by image analysis. The density of vellus hairs and the percentage of growing hairs were higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on the forehead compared with 85 hairs/cm2 with 31.5% growing hairs on the back). The rate of growth ranged from 0.03 mm/day on the forehead to 0.13 mm/day on the back. The maximum length of vellus hair significantly decreased with age; otherwise hair growth was not affected by age or sex. Some variations in hair growth and sebum secretion were observed over a period of 3 months, but no consistent rhythms were detected. There was no obvious link between vellus hair growth and sebum excretion.

Adolescent↗
PubMed1990

Correlation between the drug penetration and the blanching effect of topically applied hydrocortisone creams in human beings.

Two topical formulations of 2.5% hydrocortisone were tested to investigate the possible correlation between the blanching response of topically applied hydrocortisone and its release from the formulation after its penetration into the stratum corneum. After application of the cream, the stratum corneum was removed at different intervals and the hydrocortisone content was measured by radioimmunoassay. The blanching responses (expressed as mean score vs time) showed a 1.5-fold difference (significant at p = 0.0026) between the two creams at the maximum effect, which was reached for both creams after 16 hours. The amounts of hydrocortisone present in the stratum corneum after every application period showed a twofold difference (p = 0.0001) between the two creams. However, in contrast to the blanching, these quantities remained constant from 4 to 24 hours. This steady state characteristic may be partially due to the use of occlusion and to the excess formulation remaining at the surface. Although there is no parallelism with time between the results of the two methods, both give clear evidence of a difference in stratum corneum penetration and pharmacologic activity of the two formulations. Drug penetrations and pharmacodynamic activities of the two creams can be correlated with in vitro release characteristics.

Administration, Cutaneous↗
PubMed1990

Microbial challenge of a blood cell separator outside-seal bowl system.

The ability to store platelets beyond 24 hours requires a functionally closed system. This study tested the ability of a cell separator bowl seal system to resist penetration of microbial contamination under normal running conditions and under extreme environmental stress. Three test organisms, Micrococcus luteus, Serratia marcescens, and Staphylococcus epidermidis, were applied directly to the bowl at the edge of the seal or aerosolized and passed through the centrifuge chamber while the cell separator was run through a simulated platelet collection. A sterile, bacteriologic nutrient medium was perfused through the tubing set, thus simulating the flow of blood fractions. Following the procedure, the medium was examined for microbial growth. The concentration of aerosolized bacteria ranged from 5.2 x 10(1) to 3.9 x 10(3) colony-forming units (CFU) per mL, and the concentration of bacteria applied to the edge of the seal ranged from 1.9 x 10(5) to 2.8 x 10(9) CFU per mL. The positive control, direct inoculation of S. marcescens into the circulating medium (50 CFU/500 mL), resulted in recovery of the identical organism after 24 hours' incubation. No contamination of the system was detected in 40 experiments with aerosolized bacteria or in 32 experiments in which bacteria were applied directly to the seal. This study demonstrates that this sealed-bowl system resists microbial contamination.

Aerosols↗
PubMed1990

Use of i.v. radionuclide total body arteriography to evaluate arterial bypass shunts--a new method--a review of several cases.

Currently, Doppler ultrasound and contrast angiography are the main imaging procedures being used to evaluate arterial bypass shunts. IV radionuclide total body arteriography (TBA) is another useful imaging procedure for evaluation of bypass shunts. The authors reviewed 33 patients, 19 women and 14 men, ranging in age from forty-three to eighty-five, who had TBA done after arterial bypass surgery. Ten patients had multiple shunts and 5 had multiple follow-up studies. In total there were 80 shunts, including 43 femoropopliteal, 16 axillofemoral, 1 axillopopliteal, 13 crossover femorofemoral, and 7 aortofemoral shunts. Sixty-two of the 80 shunts were patent, 14 were occluded, and 4 had partial occlusion. The results were confirmed by Doppler studies, contrast angiograms, and/or surgical exploration without false positives or false negatives. Since the radiotracer used was 99mTc-labeled red blood cells, a MUGA study can also be performed immediately following TBA in the same injection. Twenty-eight patients had gated cardiac blood pool studies (MUGA) done; 16 had abnormal wall motion and diminished ventricular function. TBA requires only a single IV injection of radiotracer (less than 1 cc) in the upper limb. The imaging times for total body arterial and perfusion images are seventy seconds and five minutes respectively. Both total body arterial and perfusion images clearly demonstrated the entire course of shunts (single or multiple); underlying and coexisting arterial abnormalities, e g, occlusive disease (27 patients), or aneurysm (3 patients); and related perfusion changes in the extremities. TBA has unique features. It permits a complete, excellent visualization of the bypass graft without the hazard of contrast media injection. It is a simple and a virtually noninvasive procedure, particularly useful for preoperative workups and postoperative follow-ups.

Adult↗
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↗