Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.

Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.     

Creatine kinase activity in rat skeletal muscle with intermittent tetanic stimulation.

ATP synthesis from PCr through creatine kinase reaction was measured in vivo in rat leg muscle using 31P NMR magnetization transfer and progressive saturation. Both techniques determined a spin-lattice relaxation time for PCr of 3 s at rest and an identical forward rate constant of 0.22-0.26 s-1. In stimulated muscles, magnetization transfer showed that flux was not changed with a steady-state PCr of 54% of initial level. During stimulation inducing a PCr decrease to 38% of initial value, flux was significantly lowered by 30%. These findings could result from an accumulation of ions and water increases or from compartmentation of ATP and PCr in different pools either in the muscle cell or in the different muscle fibers. In addition, these results could reinforce the hypothesis against a crucial role for creatine kinase shuttle in the ATP supply in skeletal muscle.     

Exclusive elemental enteral diet in cortico-resistant and cortico-dependent forms of Crohn's disease

The aim of this study was to investigate the value of elemental diet in steroid-resistant and steroid-dependent Crohn's disease. Elemental diet (Vivonex HN, 39.4 +/- 9.2 kcal/kg/d) was delivered through a nasogastric tube at a constant rate. Twenty therapeutic periods lasting from 20 to 74 days (median, 32 days) were undertaken in 18 patients. Elemental diet was well tolerated. Mean values of hemoglobin, serum albumin, and serum transferrin increased significantly through the therapeutic period; body weight and anthropometric data did not change significantly. The short-term response to elemental diet was excellent in 11 cases, demonstrated by achievement of clinical remission and steroid withdrawal; six patients had an incomplete remission and remained slightly active or had to be maintained under low dose steroids; three patients did not respond to therapy and had to be operated upon. During the follow-up (6-30 months), 8 patients out of 17 had a relapse. Relapse was controlled by medical therapy in 5 cases and led to surgery in the 3 other cases. We conclude that elemental diet, as total parenteral nutrition, is an effective therapy of steroid-resistant and steroid-dependent Crohn's disease. However, elemental diet does not prevent relapse.     

Bronchial and cardiovascular effects of ocular topical B-antagonists in asthmatic subjects: comparison of timolol, carteolol, and metipranolol

B antagonists eye drops are most effective for the treatment of chronic open angle glaucoma. By this way of administration they have a very good systemic bioavailability. Bronchial, and cardiovascular effects of three of these topicals: timolol, carteolol and metipranolol have been evaluated in three parallel groups of asthmatic patients. The three topics induce bronchoconstriction without significant difference between them, and lower heart rate (sometimes very intensely) whatever the B antagonist studied. From these data, it is recommended to practitioners to follow carefully the rules of administration of B blockers, even in eye drops.     

Transmyocardial revascularization ameliorates ischemia by attenuating paradoxical catecholamine-induced vasoconstriction

Background  The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates ischemia by reversing paradoxical catecholamine-induced vasoconstriction. Methods and Results  Chronic ischemic cardiomyopathy was created in 11 dogs by placing ameroid constrictors on the proximal coronary arteries and their major branches. Six weeks later, 35 channels were created percutaneously in the left circumflex artery region, with the left anterior descending artery region serving as control. At rest, wall thickening and myocardial blood flow did not change in the treated region, whereas they deteriorated in the control bed. Contractile and myocardial blood flow reserve increased in the treated region but deteriorated in the control region. There was diminished iodine 123 metaiodobenzylguanidine uptake and a significant reduction in noradrenergic nerves in the treated region compared with the control region, with a corresponding reduction in tissue tyrosine hydroxylase activity. Conclusions  We conclude that the absence of a catecholamine-induced reduction in MBF reserve and contractile reserve in the TMR-treated region with associated evidence of neuronal injury indicates that the relief of exercise-induced ischemia after TMR most likely results from reversal of paradoxical catecholamine-induced vasoconstriction. These findings may have implications in selecting patients who would benefit from TMR. Supported in part by grants from the National Institutes of Health (R01-HL66034 and K-08-HL074290-01). Bethesda. Md. The radio-labeled microspheres were provided by DuPont Pharmaceuticals, North Billerica. Mass, and the ultrasound equipment was supplied by Philips. Andover, Mass. Dr Leong-Poi was the recipient of a Fellowship Training Grant from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada.