The use of nicotinamide in the prevention of type 1 diabetes.

Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.

Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects.

Adenylate cyclase activity and levels of guanine nucleotide regulatory proteins (G-proteins) were compared in platelets from normal and non-insulin-dependent diabetic (NIDDM) male subjects. Whilst no differences were noted in basal and NaF-stimulated adenylate cyclase activities the degree of stimulation achieved by both forskolin and prostaglandin, E1 was lower by some 34 and 52% respectively, in platelet membranes from diabetic subjects compared with those from normal control subjects. Altered alpha 1-adrenoceptor-mediated inhibition of prostaglandin E1-stimulated adenylate cyclase activity was evident; it being some 34% lower in platelet membranes from diabetic subjects compared to controls. Analysis of G-protein alpha-subunits, using specific anti-peptide antisera, showed that platelets from all subjects exhibited the Gi-2 and Gi-3, but not the Gi-1 forms of the inhibitory G-protein 'Gi' and all expressed the 42 kDa species of alpha-subunit of the stimulatory G-protein Gs. Whilst platelets of diabetic subjects had levels of Gs which were comparable to those found in control subjects their levels of Gi-2 and Gi-3 were some 49 and 75%, respectively, of those found in platelets from control subjects. It is suggested that changes in adenylate cyclase functioning and G-protein expression may contribute to altered platelet functioning in non-insulin-dependent diabetic subjects.

Hepatitis B in a hospital for the mentally subnormal in South Wales.

The resident population in a long-stay hospital for the mentally handicapped was surveyed in order to assess evidence for past and present infection with the Hepatitis B virus. The authors found a 0.5% prevalence of carriage of Hepatitis Be Antigen and do not recommend mass vaccination of staff and residents in this hospital.

Acetylcholine receptor antibodies in the elderly and in Down's syndrome.

Serum antibodies to the acetylcholine receptor (anti-AChR) have been reported in Japanese individuals who were elderly or had Down's syndrome at frequencies of 18% and 24%, respectively. We have measured serum anti-AChR in 3 Caucasoid groups: 53 elderly patients (aged 65-92 years) with miscellaneous (non-myasthenic) disorders, 30 individuals with Down's syndrome, and 40 elderly patients (aged 71-93 years) known to have strongly positive thyroid autoantibodies. A raised titre (greater than 0.2 nmol/l) was confined to 3 patients in the third group (7.5%). We conclude that an increased frequency of anti-AChR antibodies is not a feature of Caucasians who are elderly or have Down's syndrome, and that, even in an elderly group with a high titre of another autoantibody, the frequency of anti-AChR is lower than in elderly Japanese individuals.

Equilibrium penetration of monolayers VI: cholesterol-cetrimonium bromide system.

Equilibrium surface pressure-area isotherms for the penetration of cholesterol monolayers by the surfactant cetrimonium bromide are presented. From these isotherms, the saturation adsorptions of surfactant for various surface concentrations of cholesterol were calculated. Plots of adsorption against the inverse of the area per cholesterol molecule revealed two linear revealed two linear regions, corresponding to penetration at high and low monolayer areas. At high monolayer areas, surfactant adsorption into accessible areas of the surface was similar to adsorption at a monolayer-free surface. In this region, packing of cholesterol and surfactant molecules on the surface lowered the effective cross-sectional area of the cholesterol molecule. However, at low monolayer areas, adsorption was determined by the size of the surfactant ion and the effective area of the cholesterol molecule was equal to the collapse area of a pure cholesterol monolayer.

Equilibrium penetration of monolayers IV: dipalmitoyllecithin-centrimonium bromide system.

Equilibrium surface pressure-area isotherms of dipalmitoyllecithin monolayers were measured on substrates containing various concentrations of the surfactant, cetrimonium (hexadecyltrimethylammonium) bromide. From these isotherms, the saturation adsorptions of surfactant for various surface lecithin concentrations were calculated. Plotting of these adsorptions against the inverse of the area per lecithin molecule, as required for the "accessible area" theory, revealed two linear segments, corresponding to penetrating at high and at low monolayer areas. At both high and low areas, the adsorption into the accessible areas of the surface was similar to adsorption at a monolayer-free surface. The effective cross-sectional area of the monolayer molecule in the low area region was equal to the collapse area; in the high area region, it was equal to an area corresponding to the co-area, as calculated from the Amagat equation. The change in cross-sectional area corresponded to the transition in the monolayer from a liquid condensed state to a liquid expanded state.