The effect of nonoxinol-9, a potent non-ionic, surface-active spermicide and of the vaginal contraceptive Patentex oval containing this spermicide, on human sperm ultrastructure were studied by transmission electron microscopy. Pooled human semen was mixed either with nonoxinol-9 to give a final concentration of 1.25 or 0.05% or with Patentex oval (final concentration of the spermicide nonoxinol-9 1.25%). Saline containing no spermicidal agent served as control. After incubation at 37 degrees C for 10 min., the washed sperm pellet was processed for electron microscopy. Human spermatozoa from control experiments showed a normal ultrastructure whereas significant changes occurred after the addition of nonoxinol-9 or Patentex oval to human semen. The plasma membrane and the acrosomal membrane complex were removed. The nuclear membrane was swollen, showed breaks, discontinuities and an enlarged submembranous space. Different stages of nuclear chromatin decondensation were observed. In the middle piece, the bi-laminar membrane of the mitochondria appeared as a mono-layer membrane. The normal cristae were destroyed, the mitochondriae were empty or contained fine granular material. The observed irreversible severe membrane alterations cause an immediate devitalization of the spermatozoa and support the effectiveness of the spermicide nonoxinol-9 and the vaginal contraceptive Patentex oval.

Contraceptive Agents↗

PubMedDate not supplied

Ultrastructure of human sebaceous follicles and comedones following treatment with vitamin A acid.

Ultrastructural findings in normal human sebaceous follicles, of comedones from acne patients, and from comedones during topical treatment with vitamin A acid (VAA) are described. In normal human sebaceous follicles, the two segments of the infundibulum-the acroinfundibulum and the infrainfundibulum-show differing ultramorphological patterns of keratinization. The incomplete horny layer of the infrainfundibulum is physiological and seems to be necessary for its normal function. On the other hand, no effective barrier function is established in this region. During comedo formation, excessive keratinization takes place in the infra-infundibulum, leading to a compact and coherent horny core. VAA-treatment leads to profound alterations of keratin production, with the appearance of small, irregular, non-coherent and foamy horny cells. The comedonal wall resumes almost physiological conditions. These changes are in agreement with experimental work using VAA in vivo and in vitro and may explain the therapeutic mechanism of action of this compound in the treatment of acne.

Acne Vulgaris↗

PubMedDate not supplied

Effects of vitamin A acid in skin: in vivo and in vitro studies.

Profound metabolic changes take place in keratinizing epithelia in the presence of retinoic acid. In vivo as well as in vitro the proliferative activity of epidermal cells is greatly enhanced. Together with the increased rate of new cell production cellular differentiation (keratinization and cornification) is also altered. The effects are species-unspecific, probably tissue-specific and dose-dependent. The precise action of retinoic acid, however, still remains unknown.

Animals↗

PubMedDate not supplied

Heterogeneity of signal transduction mechanisms in human basophils and human skin mast cells. II. Effects of 7-O-methyl-UCN-01, NPC 15437 and bryostatin 1 and 2, four protein kinase C-modulatory agents, on mediator release.

Basophils and mast cells play a crucial role in immunological and allergic processes due to the release of inflammatory mediators such as histamine. It has been suggested for a long time that the histamine release (HR) from these cells is closely related to protein kinase (PKC) activity. However, the distinct role of PKC with its large variety of isozymes in different cell types and the actions of these isozymes in HR still remain unclear. Therefore, in the present study, we compared the effects of the two PKC inhibitors 7-O-methyl-UCN-01 (UCN-01-Me) and NPC 15437 as well as two PKC activators, bryostatin 1 and 2, on anti-IgE and Ca(2+)-ionophore-induced HR from human basophils and isolated human skin mast cells (HSMC). In both HSMC and basophils, anti-IgE-induced HR was inhibited by PKC inhibitor UCN-01-Me pre-incubation dose-dependently. In stark contrast, A23187-induced HR was unaffected by UCN-01-Me in both cell types. In our experiments, the inhibitory efficacy of the compound NPC 15437 on HR was much lower than that of UCN-01-Me and showed no statistical significance. Both bryostatins 1 and 2 produced good dose-dependent inhibition of HR from HSMC stimulated with anti-IgE, whereas HR from basophils was potentiated with these compounds. The same effects were observed with basophils stimulated with A23187, where potentiation of HR was up to fourfold of the control at the highest concentrations of bryostatins, while HSMC showed a slight decrease in HR compared to non-bryostatin-treated controls. Basophils and HSMC showed very clear differences in HR when directly stimulated with the bryostatins, since no HR was observed from HSMC while in basophils the HR increased up to 47% of total histamine at the highest concentrations of bryostatins (1 mumol/l). HR from basophils was observed to be strictly dose-dependent. The differences in the cell reactions of the two cell types incubated with these four compounds indicate distinct biochemical roles of PKC in the cascades leading to degranulation of the cells. Furthermore, the experiments with UCN-01-Me support the hypothesis of PKC-beta to play a substantial positive modulatory role for the degranulation of immunologically stimulated basophils.

Alkaloids↗