Evaluation of beneficial and adverse effects of glucocorticoids on a newly developed full-thickness skin model.

Glucocorticoids (GCs) are highly effective compounds widely used in the treatment of inflammatory diseases; however, they offer distinct adverse effects such as skin thinning in response to long-term topical treatment. Nevertheless it is difficult to deduce the safety of a newly synthesized compound from its structural formula. Efficient assay systems that measure beneficial and adverse effects are needed. In the present study the applicability of a three-dimensional full-thickness skin model (FTSM) is tested to display GC-induced effects regarding anti-inflammation and atrophy. It is shown that topical application of a commercial GC ointment suppresses the ultraviolet (UV)B induced induction of interleukin (IL)-6 and IL-8. Addition of purified betamethasone-17-valerate, prednicarbate and clobetasol-17-propionate to the culture medium for 14 days caused a reduction in the number of epidermal cell-layers corresponding to the atrophic risk found in vivo. Similarly, repeated topical application of five GC creams induced epidermal thinning. Evidence is given that the inhibitory effect on keratinocyte proliferation contributes to this effect. Furthermore, dermal thinning was monitored by measuring type I collagen synthesis; a decreased collagen synthesis similar to the in vivo situation is shown. The present study demonstrates the versatility of this FTSM in the validation of effectiveness and safety of GCs.     

Possibilities of surgical treatment of lesions of the organs of the reproductive system and disorders of sexual development

The authors describe the data on clinico-laboratory and instrumental examinations and surgical treatment of about 5,000 children with different reproductive organ injuries including complex patterns of abnormal sexual differentiation. The designed diagnostic programs made it possible to distribute patients into groups and according to the disease entities in conformity with the classification suggested. It is emphasized that in the developing science concerned with sex, it is necessary to distinguish an area pertaining to childhood, namely pediatric andrology, and to delineate its subject matter and tasks. Skilled assistance can be rendered by a specialized center. A broad spectrum of improved masculinizing (including the design of an artificial phallus) and feminizing (including the design of an artificial vagina from the rectosigmoid segment of the colon) is provided. The catamnestic data are evaluated.     

Differential involvement of hippocampal and amygdalar NMDA receptors in contextual and aversive aspects of inhibitory avoidance memory in rats

Adult male rats bilaterally implanted with guide canullae aimed either at the dorsal hippocampus (dHIP) or the basolateral nucleus of the amygdala (BLA) were trained in a step-down inhibitory avoidance task (IA) and tested for retention 24 h after training. Immediately after training, animals were given a bilateral infusion of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) (5.0 microg) into the dHIP or the BLA. Both intrahippocampal and intraamygdala infusions of AP5 blocked IA retention. Preexposure to the training box, but not to a different environment 24 h prior to training prevented the impairing effect of intrahippocampal infusion of AP5 on retention. Preexposure did not affect the retention impairment induced by intraamygdala infusion of AP5. These data suggest that hippocampal NMDA receptors might be involved in the contextual and spatial aspects, while amygdalar NMDA receptors might be involved in the aversive aspects of memory for IA.     

Glutamate infusion coupled with hypoxia has a neuroprotective effect in the rat

Traumatic brain injury leads to a rise in glutamate, interference with oxygen supply and secondary neuronal death in the region surrounding the primary lesion. In the present experiments we have examined the effect of combining glutamate infusion with hypoxia on both brain metabolism and neuronal death. We have used microdialysis in unanaesthetised rats with a novel dual assay for glucose and lactate to monitor the temporal relation of changes in these metabolites resulting from infusion of 100 mM glutamate alone or combined with a reduction of inspired oxygen to 8%. In a parallel series of experiments we have compared the size of neuronal lesions under the same experimental conditions. We have used MAP2 antibody staining to measure the size of the neuronal lesion. Our results demonstrate that a 30 min glutamate infusion causes an immediate increase in neuronal glucose utilisation and a rise in lactate production. When hypoxia is added during the last 15 min of glutamate infusion there is a small rise in glucose and a large additional increase in lactate. The size of the neuronal lesions produced by infusion of 100 mM glutamate is reduced by the addition of hypoxia.