A. Jarrett

THE EFFECTS OF STILBOESTROL ON THE SURFACE SEBUM AND UPON ACNE VULGARIS.

DuRiNG the past twenty years the relationship between acne viilgaris an(J the oestrogen content ofthe blood and urine has been investigated, and clinical trials of the therapeutic efFects of oestrogens in this disease have been undertaken. Wile, Barney and Bradbury (1939) estimated tlie urinary oestrogen output in twelve female acne patients and twenty controls. The average oestrogen output in the acne patients was 4-1 rat units per litre, compared with 7-7 in the controls. Later, Wile, Snow and Bradbury (1939), using an improved method of estimation, found an increased androgen/oestrogen ratio in acne patients as compared with the controls. Other workers have also investigated various aspects ofthe liormone content of blood and urine in this c(mdition (Rosenthal and Kurzrock, U)33 ; Kosenthal and Neustaedter, 1935; Combleet and Barnes, 1939; Sorba, 1939; and Hamilton, 1941). Therapeutic effects in acne patients treated with oestrogens have been reported by Van Studdilbrd (1935), Hollander and Schmitt (1939), Lawrence and Werthessen (1942), Simon (1945), Gt>eckerman (!95(l), Sulzberger and Witten (1951), Andrews d al. (1951), and Holbrook (1953). Most writers have reported good results in both sexes. Some have used very small dosages, such as 0-5 mg. of stilboestrol a day for 10 days a month, and one would be surprised if this dosage had any influence on acne. Wliitelaw (1951) observed good results in male acne patients treated with local oestrogens over prolonged periods. The effect in females was not so marked.

The dansyl chloride technique for stratum corneum renewal as an indicator of changes in epidermal mitotic activity following topical treatment

Using a hypomitotic agent, triamcinolone acetonide, and a hypermitotic agent, retinyl propionate, we investigated the relationship between epidermal mitotic activity and stratum corneum renewal time of topically treated skin as determined by the dansyl chloride staining technique.

Biological comparison of isomers and chemical forms of vitamin A (retinol)

The effects were comparcd on mouse tail scale epidermis of vitamin A acid, acetate and alcohol (all as the trans isomer) and the cis aldehyde by regular topical applications. Increases in epidermal thickness produced by different doses were compared statistically, and the induction of a granular layer and of epidermal alkaline phosphatase activity was demonstrated.

A quantitative histochemical technique for the estimation of azo dye coupling reactions.

SynopsisA quantitative histochemical method has been developed for the determination of the rate of formation of azo dye in an immediate coupling reaction for acid phosphatase. Predetermined areas of rat tail epidermis were continuously monitored by a photomultiplier. It is postulated that the rate of darkening is related to the rate of dye formation and that this in turn is dependent on the degree of enzyme activity in the area of tissue under observation. Regression coefficients were calculated for two different regions of rat tail epidermis. It was found that there was a significant difference between the transitional and lower epidermal zones:p<0.01 for 5 degrees of freedom.An aqueous model system showed that there was a relationship between the rate of dye formation and enzyme concentration. At present it is not certain whether this method can be used for the absolute estimation of enzyme in tissues, but it does appear to be satisfactory as a comparative technique.A slowing of the rate of reaction with time was clearly demonstrated and the greater the initial enzyme activity, the greater the rate of slowing. It is thought that this might be due to enzyme inhibition resulting from the azo dye formation.It is suggested that this method is relatively unaffected by variations in section thickness and this is a great advantage when cryostat sections are used. However, compression of tissue during sectioning does produce inaccuracies.

THE PENTOSE PHOSPHATE PATHWAY IN HUMAN AND ANIMAL SKIN

—The glucose-6-phosphate and glucose-1-phosphate dehydrogenases of the pentose phosphate pathway (P.P.P.) have been investigated in human, guinea-pig, and mouse skin. In areas of epidermis that have a thin granular layer, and in which the transition between living epidermal cells and the dead keratin is rapid, neither dehydrogenase can be detected. However, in regions where the transition from living to dead cells is more protracted, as occurs in palmar and plantar epidermis, mouse tail scale epidermis, the keratogenous zone of hair, and human psoriatic epidermis, there is evidence of a pentose phosphate pathway. It appears that this acts as an alternative metabolic mechanism when the mitochondrlal enzyme system is in jeopardy or destroyed. When cell death occurs quickly there is insufficient time to switch from the citric acid cycle to the P.P.P.

Enzyme changes in lichen planus

SummaryUntreated cases of lichen planus have been studied by histochemical techniques. The acid phosphatase reaction in the transitional zone has been quantitatively estimated and compared with the adjacent relatively normal epidermis. It was found that despite a thickened and accentuated granular layer as seen by routine histological methods there was a marked reduction in the intensity of the acid phosphatase reaction.The glucose-6-phosphate dehydrogenase reaction was marked in the upper layers of the epidermis in active lesions of lichen planus. This is similar to psoriasis, but different from normal human epidermis. The suggestion by other authors that lichen planus is an inborn error of metabolism is discussed.The dendritic cells of the epidermis as studied by the ATPase reaction are virtually absent in regions of active lichen planus and the possible significance of this is mentioned.The horny layer gives a dense reaction for phospholipids in lichen planus and this is similar to psoriatic keratin. The significance of this finding is considered.ZusammenfassungUnbehandelte Fälle von Lichen planus wurden mit histochemischen Methoden untersucht. Die Saure-Phosphatase-Reaktion in der Übergangzone wurde größenmäßig geschätzt und mit der danebenliegenden relativ normalen Epidermis verglichen. Der Befund ergab trotz einer verdichteten und hervorgehobenen Granulosumschicht, wie es sich bei routinemäßigen histologischen Methoden zeigt, eine deutliche Reduktion in der Intensität der Saure-Phosphatase-Reaktion.Die Glukose-6-Phosphat-Dehydrogenase-Reaktion war in den oberen Schichten der Epidermis bei aktiven Läsionen von Lichen planus auffallend vermehrt. Dieses Verhalten ist der Psoriasis ähnlich, aber unterscheidet sich von der normalen menschlichen Epidermis. Der Vorschlag anderer Forscher, wonach der Lichen planus ein angeborener Fehler des Metabolismus sei, wird diskutiert.Die mit der ATPasen-Reaktion untersuchten dendritischen Zellen der Epidermis fehlen im wesentlichen in Zonen von aktivem Lichen planus. Die mögliche Bedeutung dieser Tatsache wird erwähnt.Die verhornte Schicht ergibt beim Lichen planus eine dunkle Reaktion für Phospholipide, was dem psoriatischen Keratin vergleichbar ist. Die Bedeutung dieses Fundes wird erörtert.

Bio-assay of corticosteroids for topical application

Five commercially available corticosteroid creams were compared with respect to their thinning action on mouse tail epidermis. The greatest effects were produced by Synalar and Sintisone; hydrocortisone had the least action. In addition it was shown that the epidermal thickening induced by vitamin A could be significantly reduced by Ledercort cream. The thinning action of the fluorinated steroids on the epidermis is an important property of these agents when used for the treatment of dermatoses having a hyperactive epidermis. The mouse tail test is considered to be a useful screening test for new topical applications of these substances.

Granular layer induction following the topical application of proliferating agents

SummaryEvidence is provided for a possible dermal influence on the epidermis. Topical vitamin A stimulates a number of dermal cells with different enzyme reactions, and these invade the epidermis at about the time a granular layer is induced in mouse tail scale epidermis.N-hexadecane also induced a granular layer formation in the tail scale epidermis but the application of this agent only results in the invasion of the epidermis by non-specific esterase cells.These non-specific esterase cells are present in the follicular zone where a granular layer is usually present.It appears that dendritic cells may be responsible for the formation of a granular layer and that these cells in some way influence the keratinocytes to discharge their lyosomal enzymes and thus form a granular layer. It appears unlikely that the dendritic cells actually contribute their own acid hydrolases to the cell cytolysis necessary for the production of granular layer.ZusammenfassungDie lokale Applikation von Vitamin A stimuliert dermale Zellen, die durch verschiedene histochemische Reaktionen charakterisiert sind.N-Hexadecan induziert die Bildung einer granulären Schicht in der Epidermis des Mäuseschwanzes, ohne daß diese Zellen, die in die Epidermis einwandern, eine spezifische Esterase wie bei Vitamin A aufweisen. Diese unspezifischen Esterasezellen reichern sich in der follikulären Zone an. Dentritische Zellen scheinen mit der Bildung der granulären Schicht verknüpft zu sein, wobei die Diffusion lysosomaler Enzyme aus Keratinocyten zu erwägen ist.

THE STRUCTURE OF COLLAGEN AND ELASTIC TISSUES IN UNPROCESSED SKIN.

Di-RiNG the ])ast few years biochemists have studied collagen by modern methods, and have come to regard this structure not as a mass of fibres embedded in ground substance, but as a mixture of polymers derive<l from a parent monomer. This monomer, or unpolymerized molecule, has been named tropocollagen by Schmitt and his co-workers {Schmitt et al, l!)5n ; Gross, 1957). The unit has a length of about 20U0 A, and is tliought to contain only one, or a few, polypeptide chains, in cross-section. There is a strong tendency for end to end and lateral interaction of the particles which ultimately leads to the formation of fibres.

TREATMENT OF PSORIASIS WITH VITAMIN A

BROWN, V . K . H . & Box, V.L. (1968) Occurrence of the glyoxylate shunt in the epidermis of rats. British Journal of Dermatology, 80, 740. HALPRIN, K . M . & CHOW, D . C . (1961) Metabolic pathways in perfused dog skin. Journal of Investigation Dermatology, 36, 431KoHN, B. & LADEN, H . (1962) Studies in skin metabolism: utilization of keto-acids by rat skin homogenates. Journal of Investigative Dermatology, 38, 249. MiER, P.D. (1969) The carbohydrate metabolism of skin. British Journal of Dermatology, 81, Suppl. 2, 14. WILLIAMSON, J .R. & CORKEY, B.E. (1969) Assays of intermediates of the citric acid cycle and related compounds by fluorometric enzyme methods. Methods in Enzymology, 13, 434.