Combined fissurectomy and Botox injection for chronic anal fissure is an excellent and safe procedure with low morbidity and a high healing rate.

Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for steroids often used in clinical practice. HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes. GC and MC transcriptional activity was tested by luciferase assay in CV-1 cells transfected with human GC or MC receptor expression vectors. The 11-hydroxy-group is necessary for GC and MC receptor transactivation. As HSD2 oxidizes 11-hydroxysteroids to inactive 11-dehydrosteroids, GC and MC activity in HSD2-expressing tissues (kidney, colon) is regulated by this enzyme. As 9alpha-fluorination (such as in 9alpha-fluorocortisol) decreases oxidation by HSD2 and increases both GC and MC receptor transactivation, this modification leads to optimal, but non-selective transactivation of both receptors. Increased GC receptor and decreased MC receptor transactivation leading to more selective GC activity is reached using the following substituents: 16beta-methyl (in betamethasone), 16alpha-methyl (in dexamethasone) and triangle up 1-dehydro-configuration (in prednisolone). Whereas the modifications in position 16 decrease oxidation by HSD2, the triangle up 1-dehydro-configuration increases HSD2-activity leading to an enhanced inactivation of prednisolone compared to all other steroids. 9alpha-fluorocortisol, the most frequently used substance for MC-substitution, seems to be the best choice of available steroids for this purpose. Whereas GC selectivity can be improved by hydrophobic substituents in position 16 and the triangle up 1-dehydro-configuration, maximal GC activity needs additional fluorination in position 9alpha (such as in dexamethasone). For GC therapy directed to HSD2-expressing organs, widely used prednisolone does not seem to be the optimal recommendation.

The plasma level of free fatty acids (FFA) in adrenalectomized rats increases by 50% after treatment with aldosterone (2 microng/100 g rat). Lipolytic activity in peripheral fat tissue is lowered after adrenalectomy and doubles after in vivo administration of aldosterone to adrenalectomized rats (measured as free fatty acid release in vitro from epididymal fat tissue). Lypolysis of adipose tissue stimulated by the in vitro presence of ACTH also increases after in vivo administration of aldosterone. Incorporation of intravenously administered label from U-14C-palmitate into total extractable lipid of renal tissue is augmented 3 h after aldosterone administration to adrenalectomized rats, while no increase of the radioactivity is observed in total lipid from liver tissue. Treatment with aldosterone does not affect the total lipid content of kidney or liver in adrenalectomized rats. The oxygen consumption rate of kidney cortex slices with lactate, beta-hydroxybuterate or acetoacetate as substrates is lowered after in vivo administration of aldosterone to adrenalectomized rats. With slccinate, however, the respiratory rate of kidney slices increases after aldosterone treatment of adrenalectomized rats, the ouabain-sensitive respiration being more affected than the ouabain-insensitive respiration. An interpretation of the O2 consumption data implicating competition of lipid metabolism for CoA-SH is discussed.