all-trans-retinoic acid preserves viability of fibroblasts and keratinocytes in full-thickness human skin and fibroblasts in isolated dermis in organ culture

Human dermal fibroblast and human epidermal keratinocyte survival was examined under various conditions in organ culture. Using cell recovery from organ-cultured tissue as the criterion, it was observed that no keratinocytes and few fibroblasts survived incubation for 10-12 days in serum-free basal medium containing a low level (0.15 mM) of extracellular Ca2+. Increasing the extracellular Ca2+ concentration to 1.4 mM or treating the tissue with 3 microM retinoic acid (RA) under low Ca2+ conditions resulted in increased keratinocyte and fibroblast survival; the two treatments together were more effective than either treatment alone. The same treatments preserved fibroblast survival when pieces of isolated dermal tissue were incubated in organ culture and also supported fibroblast survival in monolayer culture. These findings indicate that recovery of keratinocytes and fibroblasts from skin after maintenance in organ culture provides a simple but definitive measure of the viability of the major cellular elements present in the tissue. These findings suggest that RA treatment enhances survival of both fibroblasts and keratinocytes and that these effects of RA can be seen at physiological Ca2+ concentrations as well as at suboptimal levels of extracellular Ca2+. Finally, these results indicate that the dermis is a direct target of RA.     

Determining heart muscle perfusion by magnetic resonance tomography progressing to clinical application

Magnetic resonance imaging detects the flow of contrast-enhanced blood and even allows the quantitative assessment of myocardial perfusion. The clinical application of this method is being held back by the difficulties in image evaluation and the limitation of standard techniques to the acquisition of a single slice per heart beat cycle. Recent developments in scanner hardware as well as in image acquisition techniques open up the possibility of assessing myocardial perfusion over the entire heart with a spatial resolution in the range of 2 mm. As an example of such a new scanning strategy, a segmented gradient-echo recalled echo planar imaging sequence with preceding saturation is discussed and results in a patient with an infarction are presented. The clinical use of perfusion assessment covering the entire heart for the diagnosis of coronary artery disease is enhanced by the flexibility of magnetic resonance imaging for the assessment of functional cardiac parameters.     

Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis

The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.