[The prevention of insulin-dependent diabetes mellitus]. / Prevenção da diabetes mellitus insulino-dependente.

At the present time, there are markers which we can use to identify individuals with a high susceptibility of developing insulin-dependent diabetes mellitus (IDDM) years before the onset of the disease. Insulin-dependent diabetes mellitus is an autoimmune disease strongly associated with HLA antigens DR3 and DR4. In this manuscript, we discuss the usefulness of several markers, such as islet cell antibodies, insulin autoantibodies and glutamic acid decarboxylase antibodies, to identify individuals with a high susceptibility to IDDM before the disease is clinically evident. Monitoring first phase insulin release during intravenous glucose administration is a useful index of residual beta cell function that can be used to detect individuals who are close to insulin dependence. Several drugs have been used to prevent the development of IDDM. These include immunodepressors, anti-inflammatory agents, non-specific immunomodulators and free radical scavengers. Due to their toxicity, studies employing aziothioprine and cyclosporin were discontinued. Other agents, such as tetrandrin and lymphotoxin, are now restricted to non-human trials. Currently, two large-scale multicentric human trials, one in Europe using nicotinamide (European Nicotinamide Diabetes Intervention Trial, ENDIT) and the other in the USA using insulin (Diabetes Prevention Trial), are now in full activity and will test the benefits of these drugs in the prophylaxis of IDDM in highly susceptible individuals.

Experimental hepatic cirrhosis in dogs caused by chronic massive iron overload.

Starting in October 1966, 19 dogs have been subjected to massive parenteral iron loading using intravenous iron-dextran and intramuscular iron-sorbitol. Although 13 animals died, in many cases the deaths were attributable to fighting. The large doses of iron employed (up to 5.8 g/kg) were well tolerated by the surviving animals, and after 35 to 47 months five of the six survivors have developed hepatic cirrhosis with massive siderosis; the dog which has not yet developed cirrhosis received the smallest iron load. The liver pathology in many ways resembles that of human haemochromatosis, and may provide an experimental model for the study of chronic iron-induced liver injury.