Biomedical subjects
Publications and source records attributed to W P Raab.
In senescence, marked changes occur on the surface of the skin and in the stratum corneum. One of the most important features is the reduced quantity of hydrolipid emulsion on the skin surface. This has to be taken into account when developing skin care for the elderly. In photoaged skin especially, tretinoin ameliorates the morphological, biochemical and functional state of the skin surface and of the stratum corneum.
A well-tanned skin is currently regarded as a sign of fitness, youth and health, with people increasingly exposing their skin to the sun and using tanning accelerators, such as psoralens, but exposure to ultraviolet B (UVB) radiation from the sun causes extrinsic ageing of the skin. The minimal erythema dose is rarely exceeded but the UVB dose that brings about irrepairable DNA damage leading to photodamage is lower. Growing numbers of patients, therefore, have prematurely aged skin with pigmented spots, dryness, itchiness and wrinkles. These symptoms are more than just of cosmetic concern. It is known that epitheliomas frequently develop in photodamaged skin; consequently, this skin requires medical treatment. Prophylactic measures should be taken from childhood, but an effective treatment for already damaged skin is topically applied tretinoin, which should be used with a mild skin cleansing and skin care programme.
A new combination of beta-carotene (25 mg) and canthaxanthin (35 mg) was clinically investigated in 74 patients with various photodermatoses and 111 patients with pigmentation disorders. The photoprotective action of this combination was ascertained in clinical experiments. Serum levels were determined in 20 patients; the absence of increased retinol levels could be confirmed. In 23 patients, ophthalmological controls did not reveal any abnormalities. In 65 of the 74 patients with photodermatoses, a satisfactory protective action was recorded. 85 of the 111 patients with depigmentations and hyperpigmentations experienced a marked decrease of the disturbing contrast between their lesions and the surrounding skin.
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The changes in cAMP, cGMP, adenylate cyclase, cyclic phosphodiesterase, and prostaglandins in psoriatic epidermal cells were compiled and critically discussed. The results of the pertinent studies permit the assumption that therapeutic approaches in psoriasis via the system of cyclic nucleotides and prostaglandins might be promising.
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All-trans retinoic acid and its derivative retinoid, two new compounds with expanding therapeutic spectrum in dermatology, were investigated in biochemical assays. Both substances provoke an increase in oxygen consumption of rat skin whereas in human skin only retinoid was found active in this respect. In resting yeast cells, both substances failed to exert any significant influence on oxygen consumption.--Pure G-6-PDH was inhibited by retinoic acid and retinoid in concentrations as low as 5 mug/ml. In human skin homogenates, LDH-, GAPDH-, and G-6-PDH-activities were inhibited by retinoic acid whereas GOT-, LAP-, and ALD-activites remained practically unchanged following an incubation with retinoic acid in concentrations between 1 and 100 mug/ml for 60 min.--The data collected in this study were briefly discussed with regard to the use of retinoic acid and its derivatives in psoriasis.
In fresh human skin homogenates, the activities of four enzymes, lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), "acid" phosphatase (AcP), and "leucine aminopeptidase" (LAP) were assayed following an incubation with hydrocortisone, hydrocotisone acetate, or hydrocortisone-17-butyrate, respectively. Concentration of the three compounds measured 2.75 mMol/l. Hydrocortison butyrate inhibited LDH-G-6-PDH-, and AcP-activities. Hydrocortisone and hydrocortisone acetate exerted a significant inhibitory action only in the case of G-6-PDH-activity.--On pure G-6-PDH from yeast, the inhibition exerted by hydrocortisone butyrate was significantly stronger than the inhibition exerted by the two other steroids. Time/action diagrams revealed the fact that hydrocortisone butyrate is superior to the other two compounds from the beginning of the incubation period.--The date sustain the assumption that hydrocortisone butyrate exerts biochemical-pharmacological actions of its own and that it may not be considered just as an esterified transport form of hydrocortisone.
The influence of D-penicillamine on glucose-6-phosphate dehydrogenase of yeast (pure enzyme), human hemolysate, and human skin homogenate were determined. In high concentrations, D-penicillamine inhibits glucose-6-phosphate dehydrogenase activity (concentrations above 6.7 mmol/l, i. e. l g/l). In low concentrations, D-penicilliamine exerts an indirect influence by removing some inhibiting metal ions, such as zinc. In human skin homogenates, an activating action of D-penicillamine on glucose-6-phosphate dehydrogenase activity occurs due to the chelation of metal ions.
Probenecid in doses of 640 mg/kg was administered to rats by the oral route, and the changes in five important enzymatic activities of urine were recorded thereafter for two days. The resluts exclude that probenecid impairs tubular reabsorption of low molecular weight protein, as urinary muramidase activity was not found increased. On the other hand, increased activities were encountered in those enzymatic activities in urine which derive from the renal tubular cells (ALD, G-6-PDH, LDH). These observations point towards a nephrotoxic effect of probenecid, which, however, is only of very low degree, as other "standard" enzymatic activities of urine, such as alkaline phosphatase, remained unchanged.
Experimental investigations were performed to elaborate the immunogenic and anaphylactoid properties of spectinomycin. In guinea-pigs, no allergy against spectinomycin could be elicited. Furthermore, the absence of immunologic cross-reactions between spectinomycin and penicillin could be confirmed. The anaphylactoid activity of spectinomycin was found to be of very low order. No mast cell degranulating action could be observed. The data collected in this study permit the statement that - as far as acute unwanted actions of antibiotics are concerned - spectinomycin is an extremely safe drug.
Betamethasone, betamethasone-17-valerate, betamethasone-17-benzoate, and betamethasone-17,21-diproprionate were investigated for their inhbitory action on glucose-beta-phosphate dehydrogenase (G-6-PDH) activity (pure enzyme from yeast, enzyme from human skin homogenate). Between these four compounds, marked differences were encountered which could not be attributed to the presence of an esterified or unesterified steroid. According to these data it does not seem to be justified to consider betamethasone esters simply as the transport forms of the topically inactive betamethasone but one must consider the betamethasone esters having biochemical actions of their own.
The changes of anthralin under various physical conditions (temperature, ultraviolet irradiation) were investigated by biochemical assay (inhibition of G-6-PDH activity), by oxygen monitor (increased oxygen consumption in the presence of zinc ions), and by recording the absorption spectra. Higher temperatures and exposure to ultraviolet light provoke the formation of a biochemically highly active compound within short periods of time. In clinical therapy, this compound may easily be formed when anthralin is used together with ultraviolet irradiation (Ingram method). Changes in the biochemical activity of anthralin are accompanied by changes in the absorption spectra. Oxidation (e.g. in the presence of zins ions) or inhibition of oxidation (e.g. in the presence of salicylic acid) may easily be detected by spectroscopic assay.
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