Plasma levels of amino acids correlate with motor fluctuations in parkinsonism

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.     

Acute effects of nitroglycerin on the energetics of the human left ventricular myocardium

We analyzed performance and efficiency of the left ventricular myocardium on the basis of two new energetic parameters. The myocardial energy consumed during one cardiac cycle is related to performed work on the one hand (E1) and to the stress-time-integral on the other (E2). E1 was obtained by analysis of the pressure-volume integral divided by left ventricular muscle mass. E2 was obtained as follows: the stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value was multiplied by a constant factor which was obtained in experimental myothermal studies. In ten patients with coronary heart disease undergoing diagnostic heart catheterization, angiocardiography was performed before and after oral administration of nitroglycerin (1.6 mg). Total energy consumption (2E1 + E2) per gram myocardium per beat decreased from 6.1 +/- 1.3 mcal/g to 4.7 +/- 1.4 mcal/g (P less than 0.01), and myocardial efficiency (E1/[2E1 + E2]) increased from 27.0 +/- 3.1% to 28.4 +/- 4.3% (N.S.) on the average. This analysis explains quantitatively the beneficial effect of nitro-preparations on myocardial function and energetics.     

Changes of lens crystallins photosensitized with tryptophan metabolites

The effect of UV irradiation on bovine lens soluble proteins (crystallins) in the presence of tryptophan metabolites was investigated in vitro. The cross-linking of crystallins by UV irradiation was accelerated by kynurenine, 3-hydroxykynurenine, anthranilic acid and 3-hydroxyanthranilic acid. On denaturation of crystallins by photooxidation, alpha-crystallin was characterized by the formation of water-soluble HMW (high molecular weight) protein, while water-insoluble HMW protein was produced from beta- and gamma-crystallin. These HMW aggregates showed cross-linking by non-disulfide covalent bonds. LMW (low molecular weight) peptides were formed by degradation of alpha- and beta-crystallin.