Mitotic index of psoriatic lesions treated with anthralin, glucocorticosteriod and occlusion only
TL;DR: Nine patients with psoriasis were studied with regard to the effect of local medication on the mitotic index and Cordran® tape, anthralin and Blenderm® tape were compared with an untreated control.
About: This article is published in Journal of Investigative Dermatology.The article was published on 1970-05-01 and is currently open access. It has received 74 citations till now. The article focuses on the topics: Mitotic index.
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TL;DR: Assessment of permeability barrier function, lamellar body structure, and extracellular lameLLar bilayer formation in untreated patients with different psoriatic phenotypes indicates that both the initial appearance of psoriasis and changes in disease phenotype are driven by alterations in barrier function.
191 citations
TL;DR: A previously unrecognized pharmacological event, acute tolerance to the vasoconstrictive action of topically applied glucocorticosteroids, has been discovered in human skin and these observations have important applications to optimum timing in the clinical topical use of glucoc Corticosteroid for maximum therapeutic advantage.
Abstract: A previously unrecognized pharmacological event, acute tolerance to the vasoconstrictive action of topically applied glucocorticosteroids, has been discovered in human skin. Thus, potent topical glucocorticosteroids will cause vasoconstriction when first applied to human skin but with subsequent applications the production of vasoconstriction rapidly diminishes. However, after a rest period of a few days, the same initial vasoconstrictive effect may be produced again, but this will also disappear if the steroid is again continued topically. These observations have important applications to optimum timing in the clinical topical use of glucocorticosteroids for maximum therapeutic advantage.
133 citations
TL;DR: It is found that repeated barrier disruption by topical acetone treatment or tape stripping induced epidermal hyperplasia in the flank skin of hairless mice and the ear of ICR mice, as well as inflammation in ear skin, indicating that manipulations of the stratum corneum which disrupt the permeability barrier induce a variety of biologic responses in the underlying epidermis.
Abstract: Acute disruption of the permeability barrier produces marked changes in epidermal metabolism, including increased lipid synthesis, increased DNA synthesis, and the enhanced production of cytokines. Because abnormalities in the barrier are present in a wide variety of skin disorders, we hypothesized that barrier disruption may be an important event that initiates pathological changes in the skin. In the present study, we found that repeated barrier disruption by topical acetone treatment or tape stripping induced epidermal hyperplasia in the flank skin of hairless mice and the ear of ICR mice, as well as inflammation in ear skin. The degree of epidermal hyperplasia correlated with the level and duration of barrier disruption. Likewise, the epidermal mitotic index, which was localized to the basal layer, increased with repeated disruption, indicating that the hyperplasia could be ascribed to increased cell proliferation. However, occlusion with a water-impermeable membrane, which prevents water loss, did not prevent the epidermal hyperplasia. Moreover, immunohistochemical staining for TNFα and IL 1α increased following repeated acetone treatment or tape stripping, and this increase also was not blocked by occlusion. These studies indicate that manipulations of the stratum corneum which disrupt the permeability barrier, such as, repeated acetone treatment or tape stripping, induce a variety of biologic responses in the underlying epidermis. Since neither the increase in epidermal cytokine production nor the described changes in cutaneous pathology were prevented by occlusion, in these two models the changes should not be attributed to increased water loss, but rather to epidermal injury resulting in the production and release of epidermal cytokines.
128 citations
TL;DR: The antimitotic activity of the corticosteroids seems to be related to their therapeutic efficacy, and may supplement the vasoconstrictor assay for pertinence to those diseases with increased cell turnover.
Abstract: The action of the corticoid drugs has been investigated in regard to their antimitotic activity on human skin. For topical studies two 4-mm biopsies were taken from the forearms of each volunteer to allow use of the paired comparison method; a separate control group was used for oral studies. The results indicated that orally administered triamcinolone and topically administered triamcinolone acetonide inhibited mitotic activity of the epidermis. Topically administered 0.2% fluocinolone acetonide proved equally potent, although no effect was seen when 0.025% was used. No mitotic inhibition was observed after topical administration of hydrocortisone acetate. Repeated injections of corticotropin, however, resulted in a significant fall in mitotic activity. The antimitotic activity of the corticosteroids seems to be related to their therapeutic efficacy. This may supplement the vasoconstrictor assay for pertinence to those diseases with increased cell turnover.
122 citations
TL;DR: The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.
Abstract: Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.
106 citations
References
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Book•
01 Dec 1969TL;DR: In this paper, the authors introduce statistical analysis and introduce the concept of statistical analysis in statistical analysis, and propose a framework for statistical analysis for the analysis of statistical data in the literature.
Abstract: Introduction to statistical analysis , Introduction to statistical analysis , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
5,255 citations
TL;DR: A test of the hypothesis would be to determine whether the histologic and cytologic changes occurring in the epidermis during healing of the lesion of psoriasis are similar following the different therapeutically effective agents.
158 citations
Journal Article•
TL;DR: It must be emphasized that knowledge not only of cell division, but also of many fundamental biochemical changes related to cellular growth, has benefited from work with mitotic inhibitors, and that the antimitotic properties of so many natural substances-hormones, plant extracts, antibiotics-indicate that the various types of mitotic inhibition belong to general biology, and their study helps to understand better the normal control of mitosis.
Abstract: At this point, it may appear that, although only a small number of the mitotic inhibitors has been considered, the problem of antimitotic action remains rather confused. Clear-cut classifications are no longer possible; in the same group of substances ( e.g. , the steroid hormones) actions are to be found varying between mitotic stimulation and selective inhibition of one of the steps of mitosis. Moreover, several substances may affect either spindle or chromosomes, depending on the experimental conditions. The biochemical basis of most antimitotic action is shrouded in obscurity, even though some discoveries about the chemistry of the mitotic apparatus, the role of folic coenzymes in nucleic acid metabolism, the structure of the spindle fibers, and the antagonists of mitotic poisons, open the path for further clarifications of the subject.
It was pointed out several years ago (64) that mitotic poisons appeared far more promising in the biochemical analysis of cellular division than in cancer chemotherapy. Since then, thousands of drugs have been tested, and so far, the only ones which have found some use in medicine remain dangerous, for the fundamental reason that they are mitotic poisons, and that some normal tissues grow faster than many neoplastic ones. If an antimitotic substance acting selectively on neoplastic growth is to be discovered, it should have no action on normal cells. That such a possibility may exist is indicated by the rare examples of mitotic antagonists with a specific action on some tissues: for instance, cortisone vs. lymphoid tissue, and griseofulvin vs. skin.
On the positive side, it must be emphasized that knowledge not only of cell division, but also of many fundamental biochemical changes related to cellular growth, has benefited from work with mitotic inhibitors. The study of DNA synthesis, the isolation of the mitotic apparatus, morphological studies of chromosomes, have considerably progressed because some of the mitotic poisons have proven to be useful tools.
Mitotic inhibitors are more than possible drugs for cancer chemotherapy; they are tools which enable the cytologist to dissect the interrelated phases of the mitotic cycle. This type of approach would certainly be facilitated if more nearly uniform methods were used. On the other hand, chance observations, like those which led to the discovery of griseofulvin and vinblastine (155), will always play a fundamental part in the development of science.
It should be evident from this review that many important aspects of mitosis have not been touched by the use of mitotic inhibitors. The reduplication of the centrioles (a remarkably complex phenomenon), the disappearance and synthesis of the nucleolus, the mechanisms of cleavage, the modifications of cell surface, the multiplication of mitochondria and other cell organelles, the control of mitosis itself in the pluricellular animal, remain poorly understood. Mitosis in plants and animals appears to be quite similar, and many mitotic poisons, among them the most active, act similarly on both. Cortisone, however, would never had been found to have an antimitotic action if only plant cells had been used. In pluricellular organisms, growth may be controlled by organ-specific substances that inhibit mitosis, but these remain to be isolated.
Apart from the pharmacological and toxicological aspects of these problems, it should be pointed out in fine that the antimitotic properties of so many natural substances-hormones, plant extracts, antibiotics-indicate that the various types of mitotic inhibition belong to general biology, and that their study helps to understand better the normal control of mitotic activity.
77 citations
TL;DR: It is shown that in low concentrations hydrocortisone has little if any antimitotic activity, that when it is present together with chalone and adrenalin it does not markedly increase their antimitotics activity, but that it does act to prolong the mitotic depression which they induce.
Abstract: It has previously been established that the epidermal chalone inhibits epidermal mitotic activity more powerfully in the presence of adrenalin, although adrenalin itself is not a mitotic inhibitor. It is now shown that in low concentrations hydrocortisone has little if any antimitotic activity, that when it is present together with chalone and adrenalin it does not markedly increase their antimitotic activity, but that it does act to prolong the mitotic depression which they induce.
It is known that, without hydrocortisone, adrenalin rapidly escapes from epidermal cells so that the chalone action is weakened. It appears that the role of hydrocortisone may be to reduce the rate of adrenalin loss and thus to prolong the chalone-adrenalin activity.
It is also shown that the rate of loss of adrenalin from epidermal cells is inhibited, though to a much lesser extent, in the presence of excess chalone.
70 citations
TL;DR: Mitotic counts and histological features have been studied in 35 psoriatic patients prior to treatment, and during treatment with topically applied fluocinolone acetonide, methotrexate, dithranol and coal tar.
Abstract: SUMMARY. —Mitotic counts and histological features have been studied in 35 psoriatic patients prior to treatment, and during treatment with topically applied fluocinolone acetonide, methotrexate, dithranol and coal tar.
Prior to treatment there was considerable variation in the mitotic counts in the 35 biopsies. The granular layer was absent in 10 biopsy specimens, partially formed in small areas in 21, well formed in most areas in 2, and normal in 2. There was no correlation between the mitotic counts and state of the granular layer.
With methotrexate and dithranol treatment the granular layer showed improvement prior to a significant fall in the mitotic counts. With fluocinolone acetonide the improvement in the granular layer appeared at the same time as a significant fall in the mean mitotic count, but the granular layer had completely reformed in 7 of the 9 patients while the mitotic count was still considerably raised compared to uninvolved psoriatic skin. With coal tar the results were not uniform; some patients showed a significant fall in mitotic counts prior to improvement in the granular layer and others first showed improvement in the granular layer.
It is suggested that in clearing psoriasis these drugs have an action other than, or in addition to, inhibiting mitosis.
59 citations
"Mitotic index of psoriatic lesions ..." refers background in this paper
...Fry and McMinn (1) have demonstrated a decrease in mitotic index in psoriatic lesions with topical glucocorticosteroids and anthralin TABLE Mitotic Index (No. of Mitoses Per 1000 Cells)* Pt....
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...Fry and McMinn (1) demon trated a decrease in the mitotic ind x of psoriatic plaque after the topical application (under occlu ion) of methotrexate, glucocorticosteroid and anthralin....
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...Fry and McMinn (1) have demonstrated a...
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