Pharmacology and toxicology of azelaic acid.

The results of general pharmacological studies on metabolism, smooth muscles, renal function, cardiovascular and neurotropic effects do not contra-indicate the specific surface use of azelaic acid. From specific pharmacologic studies it is assumed that azelaic acid exerts its therapeutic effect in acne by an antimicrobial, probably bacteriostatic, effect on acne-relevant microorganisms such as Propioni bacerium acnes and, in addition, by a strong comedolytic effect. In numerous studies it has been demonstrated that azelaic acid is not toxic.

Perspectives in corticosteroid research.

In dermatotherapy, potent drugs are needed which can be used as alternatives to corticosteroids, but which are without unwanted local and systemic effects. Three theoretical possibilities for the development of such advanced drugs have been presented. Firstly, dissociation of wanted and unwanted effects by selection of a certain corticosteroid structure is proposed. However, this is impossible, because corticosteroid receptors are ubiquitous and all display the same specificity. Secondly, manipulation of the pathways of the inflammatory response may be more feasible. Because of increasing knowledge of the mechanism of inflammation and the pathogenesis of cutaneous inflammatory diseases, it is predictable that effective nonsteroidal anti-inflammatory drugs for topical use will be developed some time in the future. Lastly, the effects and side effects can now be limited to the site of application, thus avoiding systemic risks, by optimising corticosteroid activity with respect to receptor binding and pharmacokinetic properties. However, it is realistic to assume that, even in the future, corticosteroids will always possess both desirable and undesirable properties.

Pharmacology of antiandrogens.

Principally, antiandrogens affect all androgen-dependent organs and functions as for instance accessory sexual glands, spermatogenesis, skin and skin appendages, libido and potency, male sexual differentiation, longitudinal bone growth and bone maturation. Pharmacologically, it is important to distinguish between the steroidal antiandrogens of the cyproterone acetate type and the nonsteroidal pure antiandrogens (flutamide, anandrone). For the clinical use of cyproterone acetate and similar antiandrogens in both men and women the three main properties are important: Cyproterone acetate is antiandrogenic, it is a quite potent progestogen and it is antigonadotrophic. Based on pharmacological and biochemical backgrounds cyproterone acetate is used in the following indications: Androgen mediated disorders of the skin such as acne, seborrhoea, hirsutism, alopecia, advanced prostatic carcinoma, precocious puberty and male hypersexuality. In order to avoid undesired systemic side effects local application of antiandrogens, e.g. of cyproterone acetate, has been tried several times. All these attempts have failed probably because insufficient concentration of the antiandrogen at the pilo sebaceous unit. 17 alpha-propylmesterolone is active when given topically (hamster ear model) and has no systemic antiandrogenic effects. This antiandrogen is highly lipophilic and does penetrate preferentially through the hair follicle as has been shown by autoradiography.

Immunocytochemical localization of uteroglobin in the genital tract of male rabbits.

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.

Antigenicity of human chorionic gonadotrophin preparations in men.

The antigenicity of HCG was tested in twenty-three young healthy men receiving two different HCG preparations (A and B). Each subject received 5000 i.u. HCG intramuscularly daily for three consecutive days, followed by another course, 3 weeks later, of 5000 i.u. HCG injections daily for 3 days. Two of the fifteen subjects treated with preparation A developed HCG antibodies in response to the HCG injections. The results show that although HCG is of human origin and also occurs normally in men, it may induce antibody formation even after brief treatment.

Recombinant plasmids with genes for the biosynthesis of alkaline phosphatase of Escherichia coli.

Restriction maps of several recombinant plasmids representing a section of the E. coli K12 chromosome 35,000 bp in size with the genes phoA, proC and phoB were prepared. The orientation of phoA and the exact position of its N-terminal end on this map were determined by identifying a subfragment which carried the phoA promoter and by determining the nucleotide sequence of a 160 bp portion of this subfragment comprising the codons for the N-terminal end of pre-alkaline phosphatase. From this DNA sequence the leader sequence of alkaline phosphatase which consists of 21 amino acids was derived.

[Studies on the Pharmacology of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolon valerate) (author's transl)]. / Untersuchungen zur Pharmakologie von 6alpha,9-Difluor-11beta-hydroxy-16-methyl-21-valeryloxy-1,40pregnadien-3,20-dion(Diflucortolonvalerianat)

The topical and systemic anti-inflammatory action of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) was studied in the rat in comparison with fluocortolone, diflucortolone and some other corticoids. In addition the effect of the compounds studied on the following parameters of corticoid activity was examined in the rat: body weight and weights of thymus, spleen and adrenals; blood sugar concentration and liver glycogen content; diuresis and Na+ and K+ elimination with the urine; the binding of diflucortolone and some diflucortolone-21-esters to the cytoplasmic corticoid receptor of the rat's thymus was also determined. In all tests diflucortolone was shown to be a corticoid with very potent topical and systemic action. Diflucortolone valerate showed the same potent anti-inflammatory action on topical application as the unesterified compound. After subcutaneous administration, however, the systemic corticoid action of the valerate was considerably inferior to that of diflucortolone on account of the kinetics of the more lipid soluble ester.