Tolcapone prolongs "on" time in fluctuating parkinsonian patients while allowing a reduction in daily levodopa dosage, thereby improving the efficacy of long term levodopa therapy.

The role of calcium-activated degenerative processes in the efflux of enzyme from experimentally damaged mouse muscle has been studied using an isolated mouse soleus muscle preparation. Inhibition of mitochondrial activity with dinitrophenol or sodium cyanide was found to cause a large efflux of enzyme. This was largely prevented by withdrawal of the extracellular calcium suggesting that mitochondrial calcium overload does not play a major role in the damage leading to enzyme efflux. Treatment of the muscles with a variety of protease inhibitors had no effect on the enzyme efflux from muscles following exhaustive contractile activity indicating that activation of protease activity is not a major factor in the damaging process. Certain inhibitors of phospholipase-A activity (i.e. dibucaine, chlorpromazine and mepacrine) have been found to significantly reduce the enzyme efflux following treatment of the muscles with dinitrophenol, although other phospholipase inhibitors were without effect. It is suggested that the changes in muscle membrane permeability leading to enzyme efflux following experimental muscle damage are probably the result of calcium-mediated activation of phospholipase A leading to changes in membrane phospholipid metabolism.

The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.

The electrical resistivity of lung tissue can be related to the structure and composition of the tissue and also to the air content. Conditions such as pulmonary oedema and emphysema have been shown to change lung resistivity. However, direct access to the lungs to enable resistivity to be measured is very difficult. We have developed a new method of using electrical impedance tomographic (EIT) measurements on a group of 142 normal neonates to determine the absolute resistivity of lung tissue. The methodology involves comparing the measured EIT data with that from a finite difference model of the thorax in which lung tissue resistivity can be changed. A mean value of 5.7 +/- 1.7 omega(m) was found over the frequency range 4 kHz to 813 kHz. This value is lower than that usually given for adult lung tissue but consistent with the literature on the composition of the neonatal lung and with structural modelling.

Much of the current literature regarding the biological effects of antioxidant nutrients has concentrated on their potential role in inhibiting or preventing tissue damage induced by free radical species produced during metabolism. Recent findings indicate that antioxidants may also have more subtle roles, regulating changes in gene expression induced by oxidizing free radical species. There is increasing evidence that free radicals act as signals for cell adaptation in a variety of cell types and the nature of the mechanisms by which free radical species influence gene expression is the subject of much current research. Processes such as these may be particularly important in tissues regularly exposed to varying amounts of oxidative stress as part of their normal physiological functions. Examples of such tissues include skin exposed to u.v. light and skeletal muscle subjected to repeated bouts of exercise.