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Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.We performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200 μg day(-1) eprotirome or placebo for 12 weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures.Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients.In hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.

During 1987 and 1988 all patients undergoing a cataract extraction at the eye Clinic of Sahlgrenska University Hospital were registered to determine the yearly incidence of cataract extractions according to sex and age. We found that after the age of 70 years the incidence of cataract extractions was higher for females than males. This difference was most pronounced for operations of the first eye. In this case the relative risk to undergo a cataract extraction for a woman compared to a man was 1.71 with 95% confidence interval 1.51-1.94, which showed a significantly increased risk. The preoperative VA of the best eye at the time of the first operation did not differ significantly between older men and women, indicating that women had no tendency to come earlier to operation. Our results show that after the age of 70 years the operation incidence of women is significantly higher than for men. This probably reflects a generally increased prevalence of various stages of cataract among females above 70 years in a Nordic population.

KB130015 (KB015), a new drug structurally related to amiodarone, has been proposed to have antiarrhythmic properties. In contrast to amiodarone, KB015 markedly slows the kinetics of inactivation of Na(+) channels by enhancing concentration-dependently (K(0.5) asymptotically equal to 2 microM) a slow-inactivating I(Na) component (tau(slow) asymptotically equal to 50 ms) at the expense of the normal, fast-inactivating component (tau(fast) asymptotically equal to 2 to 3 ms). However, like amiodarone, KB015 slows the recovery from inactivation and causes a shift (K(0.5) asymptotically equal to 6.9 microM) of the steady-state voltage-dependent inactivation to more negative potentials. Despite prolonging the opening of Na(+) channels KB015 does not lengthen but often shortens the action potential duration (APD) in pig myocytes or in multicellular preparations. Only short APDs in mouse are markedly prolonged by KB015, which frequently induces early afterdepolarizations. KB015 has also an effect on other ion channels. It decreases the amplitude of the L-type Ca(2+) current (I(Ca-L)) without changing its time course, and it inhibits G-protein gated and ATP-gated K(+) channels. Both the receptor-activated I(K(ACh)) (induced in atrial myocytes by either ACh, adenosine or sphingosylphosphorylcholine) and the receptor-independent (GTPgammaS-induced or background) I(K(ACh)) are concentration-dependently (K(0.5) asymptotically equal to 0.6 - 0.9 microM) inhibited by KB015. I(K(ATP)), induced in atrial myocytes during metabolic inhibition with 2,4-dinitrophenol (DNP), is equally suppressed. However, KB015 has no effect on I(K1) or on I(to). Consistent with the effects in K(+) currents, KB015 does not depolarize the resting potential but antagonizes the APD shortening by muscarinic receptor activation or by DNP. Intracellular cell dialysis with KB015 has marginal or no effect on Na(+) or K(+) channels and does not prevent the effect of extracellularly applied drug, suggesting that KB015 interacts directly with channels at sites more easily accessible from the extracellular than the intracellular side of the membrane. At high concentrations KB015 exerts a positive inotropic action. It also interacts with thyroid hormone nuclear receptors. Its toxic effects remain largely unexplored, but it is well tolerated during chronic administration.