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Accumulating evidence supports the popular notion that psychological stress states may accelerate aging. Stress has been shown to influence cellular systems known to be involved in the aging process. Furthermore, stress is associated with an increased risk of various age-related medical disorders. These effects are likely mediated by the secretion of stress hormones. In this short review we focus on biochemical and epidemiological evidence for a link between stress and aging.

Exclusively private companies do drug development. The State contributes with education of academics and basic research constituting the basis of half of the drugs developed by the private companies. The Danish private drug research amounts to six billion DKK per year, corresponding to the estimated price of the development of one new drug. The development shows a negative tendency. There are doubts about the scientific credibility, the number of new drugs is declining, drug development costs are rising, and the competitiveness in Europe is declining compared with the one of The United States. Continued improvement of Danish drug development can be achieved by stimulation of the public research related to drug development.

Reactive free oxygen radicals are formed in the reactions involved in normal cell metabolism. This formation is closely regulated e.g. by dietary antioxidants. Present knowledge suggests that an imbalance, with surplus of free radicals, can play a role in the pathogenesis of certain types of cancer, atherosclerosis, and cataract. A number of epidemiological studies have demonstrated a reduced risk of developing these diseases in persons who consume a diet with a high content of vegetables and fruit, which contains large quantities of the antioxidants: beta-carotene, vitamins C and E. Intervention studies, using supplements of these antioxidants, have so far not been able to show a beneficial effect. The apparently protective effect of fruit and vegetables may be due to other active ingredients. In Denmark the average intake of vegetables and fruit is low, and it is estimated that an increased consumption of these foods could reduce the occurrence of certain cancer types and atherosclerosis. In contrast, there is no evidence that antioxidant supplements would provide protection against disease, and their safety remains to be established.

Nitroglycerin and other organic nitrates are beneficial in ischaemic heart disease and myocardial infarction and as adjunctive therapy in congestive heart failure. The nitrates are inactive prodrugs, and their vascular effects depend on metabolic conversion to vasoactive intermediates like nitric oxide and/or nitrosothiols with subsequent stimulation of guanylate cyclase causing increased formation of cyclic GMP. The compounds relax vascular smooth muscle producing venous dilatation at low concentrations and at higher concentrations dilation of coronary arteries and collaterals and systemic arterial vessels. Nitrate tolerance is, however, a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or with the use of long-acting nitrates or transdermal applications resulting in constant plasma concentrations. Therapeutic strategies should be designed to provide a daily low-nitrate period or nitrate-free period to obviate the development of tolerance and thus maintain the antianginal effects.

Reduced glutathione (GSH) is the main intracellular non-protein thiol compound. GSH is important in a variety of reactions including reductive processes, protection of cells against oxidative stress, free oxygen species and other toxic compounds of endogenous and exogenous origin. In the cardiovascular field, thiol compounds may protect against ischaemia-reperfusion injuries, regulate enzyme activities and modify the function of organic nitrates and vascular tone. Metabolic manipulation with thiol compounds (i.e. by treatment with N-acetylcysteine or oxothiazolidine) may provide a safe method for protecting cells against ischaemia and may be a relevant supplement to current cardiovascular therapy.

During 1978-1987 the annual sale of analgetics increased by 28% to 164 millions defined daily doses (mDDD) per year. Paracetamol changed status to over-the-counter drug by 1.1.1984 as did combinations of acetylicsalicylic acid and codein 14.5.1984. The consumption of paracetamol increased rapidly to 47 mDDD/-year, the mortality steadily decreasing to 0.07 deaths/mDDD in 1986. The consumption of salicylics decreased from 113 to 94 mDDD, of which the salicylic/codein combination constituted an increasing fraction. The mortality of salicylics increased from 0.05 death/mDDD in 1983 to 0.27/mDDD in 1986. Opoids except dextropropoxyphene increased three times during the period, while the risk of fatal poisoning decreased from 10 to 5 deaths/mDDD. Dextropropoxyphene consumption was stable 1978-86 while mortality doubled from 59 to 121 per year. After a National Board of Health initiative, 66 dextropropoxyphene deaths were seen in 1987. Paracetamol mortality was 10 times lower than in England and Wales, where a dextropropoxyphene/paracetamole combination (not available in Denmark) was often involved. From a toxicological point of view over the counter status for combinations of strong and weak analgetics are not desirable.