No abstract

No abstract

Objective: Preclinical characterization of methylprednisolone aceponate. Results: The local antiinflammatory potency of methylprednisolone aceponate was equal to the very strong glucocorticoid clobetasol 17‐propionate but higher than the potency of hydrocortisone 17‐butyrate after topical application in 2 animal models of inflammation. Methylprednisolone aceponate is activated enzymatically in the skin. This activation proceeds faster in inflamed tissue. In contrast to clobetasol 17‐propionate, methylprednisolone aceponate was devoid of systemic effects after topical application for 3 days. Finally, whereas clobetasol 17‐propionate induced marked skin atrophy, methylprednisolone aceponate induced only slight atrophogenic changes after long‐term application (up to 43 days) on rat skin, comparable to the effects of hydrocortisone 17‐butyrate. Conclusions: Methylprednisolone aceponate combines high local antiinflammatory potency with very low systemic side effects and only minor local atrophogenic activity. The reason for the dissociation between local antiinflammatory and atrophogenic effects is not known so far. It may be speculated that one of the reasons for the very strong local antiinflammatory activity may reside in the faster enzymatic activation in inflamed tissue. Methylprednisolone aceponate represents a new corticosteroid with which it is possible to improve the dissociation between desired antiinflammatory activity and undesired side effects of topical glucocorticoids.

Using the immunoperoxidase technique and specific goat anti-serum to uteroglobin, selective immunochemical staining products are localized in the epididymal epithelium of the caput and proximal corpus region, at the adluminal border of the cauda epididymidis and, as well known, in epithelial cells of the endometrium of pregnant and progesterone-treated rabbits. Specific staining is also seen on spermatozoa. A uteroglobin-like antigen has been similarly localized in alveolar and bronchial epithelial cells of the lung. Testis, prostate, seminal vesicle and ductus deferens do not seem to contain in their tissues immunoreactive uteroglobin-like antigens. Similarly, the uterus and ductus epididymidis of immature rabbits are devoid of immunoreactivity. The presence of uteroglobin-like antigens in tissues other than the endometrium, particularly the ductus epididymidis, stimulates new discussions on the function of this protein in reproductive physiology and fertility research.

No abstract

Hormone receptors are proteins located on the cell membrane or in the cell cytoplasm. Their function is to recognize and bind the respective hormone; the biological action of the hormone originates from the hormone-receptor complex. Specific receptors have been found for all known hormones. Monitoring the equilibration between hormone, receptor, and hormone-receptor complex ("determination of receptor binding") permits quantitative determinations of hormones, allows the characterization of endocrinal disturbances, and contributes to the elucidation of structure-affinity relationships.

No abstract

Prostacyclin (PGI2) and prostaglandin E2 were reported to enhance oedema formation in skin, when studied in experimental models of inflammation (Williams, 1979). This phenomenon was attributed to their vasodilating activities, and it was concluded that prostaglandins are endowed with a proinflammatory activity.As PGI2 is only of limited stability in aqueous solution, difficulties in the interpretation of dose-related responses were overcome by the availability of a stable prostacyclin analogue ZK 36 374(Skuba]Ia& Vorbriiggen, i98i)Cfor structure see Fig. i). ZK 36 374 is characterized by a profile of pharmacological and biochemical effects known for the parent compound (Schror er aL, 1981).The aim of this study was to establish the influence of topically applied ZK 36 374 on cutaneous blood flow and oedema formation and to evaluate its possible proinflammatory potential. RESULTSThe vasodilator activity of ZK 36 374 resulting in hyperaemia was assessed in the shaved dorsal skin of conscious rabbits. A non-invasive technique, measuring the Doppler signal of a laser beam was applied to evaluate blood flow. As shown in Figure t, blood flow increases in a dose-related manner when ZK 36 374 is administered topically. The lowest effective dose for vasodilation was 600 ng. Hyperaemia was measured after 3 h, a period after which all doses produced maximal effects. Blood flow returned to normal after approximately 5-6 h (600 ng) or 24 h (60 fig) (not shown).Although the rate of penetration for skin is unknown for ZK 36 374, the long-lasting and dose-dependent hyperaemia suggest a slow release from a reservoir-most likely the stratum corneum, since the half life in plasma was found to be approximately 15 min.The influence of vasodilation produced by ZK 36 374 on oedema formation was assessed by measuring Evans' blue leakage induced by either histamine or croton oil. ZK 36 374 was applied 3 h before intradermal injection of histamine and the plasma leakage was determined 30 min thereafter. Croton oil was applied together with ZK 36 374 topically and the oedema volume was measured after 5 h. Oedema volume was determined photometrically as cxtravasatcd dye and related to the blood concentration of Evans' blue.144