In a milieu of adhesive macromolecules, lipids and inflammation-sensitive proteins including fibrinogen, total cholesterol, triglycerides, hs-CRP and immunoglobins G, M and A, fibrinogen has a dominant role in maintaining the red blood cell adhesiveness/aggregation in the peripheral venous blood. These findings are relevant for the research directed at finding new apheretic modalities to reduce the degree of red blood cell adhesiveness/aggregation in the peripheral blood.

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We gave pharmacologic doses of choline to patients with tardive dyskinesia in an attempt to suppress involuntary facial movements. Choline is the physiologic precursor of acetylcholine, and its administration elevates brain acetylcholine levels in laboratory animals and, possibly, in human beings. Hence, we thought that its use could benefit patients with diseases like tardive dyskinesia, which is believed to result from deficient central cholinergic tone. Twenty patients with stable baccal-lingual-masticatory movements took oral doses of choline for two weeks according to a double-blind crossover protocol. Plasma choline levels rose from 12.4 +/- 1.0 to 33.5 +/- 2.5 nmol per milliliter (mean +/- S.E.M.; P less than 0.001) during this period. Choreic movements decreased in nine patients, worsened in one and were unchanged in 10. Thus, oral doses of choline can be useful in neurologic diseases in which an increase in acetylcholine release is desired.

Consumption of a single meal containing lecithin, the major source of choline occurring naturally in the diet, increased the concentrations of choline and acetylcholine in rat brain and adrenal gland. Hence, the concentration of acetylcholine in the tissues may normally be under direct, short-term nutritional control.

Groups of rats were deprived of food overnight and then given free access to diets designed to raise (carbohydrate) or lower (carbohydrate and large neutral amino acids) brain tryptophan concentrations. Similar diets were supplemented with 40% fat and fed to other groups. All animals were killed 2h after food presentation. Sera from animals fed carbohydrate plus fat contained 2.5 times as much free tryptophan concentrations did not differ. Similarly, sera from rats fed on carbohydrate, large neutral amino acids, and 40% fat contained 5 times as much free tryptophan as those from rats given this meal without fat, but brain tryptophan concentrations increased by only 26%. Correlations were made between brain tryptophan and (1) free serum tryptophan, (2) the ratio of free serum tryptophan to the sum of the other large neutral amino acids in serum that compete with it for uptake into the brain, (3) total serum tryptophan or (4) the ratio of total serum tryptophan to the sum of its circulating competitors. The r values for correlations (3) and (4) (i.e. those involving total serum tryptophan) were appreciably higher than those for correlations (1) and (2). Brain tyrosine concentrations also were found to correlate well with the ratio of serum tyrosine to the sum of its competitors. Competition for uptake into the brain among large neutral amino acids (represented here by serum ratios) thus appears to determine the changes in the brain concentrations of these amino acids under physiological conditions(i.e. after food consumption). Total, not free, serum tryptophan is the relevant index for predicting brain tryptophan concentrations.

Twenty-four hours after rats receive choline chloride (20 mmol/kg, by stomach tube) the activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] increases by 31% within adrenomedullary chromaffin cells. This treatment also causes major elevations in the levels of choline and acetylcholine within the adrenal gland; however, acetylcholine levels return to normal by 16 hr after the choline is given. The daily administration of 10 or 20 mmol/kg of choline for 4 days elevates adrenal tyrosine hydroxylase activity by 29% or 51%, respectively. Such increases in tyrosine hydroxylase activity are not observed in animals given ammonium chloride, another basic chloride-containing compound, by stomach tube or in animals treated with cycloheximide, an inhibitor of adrenal protein synthesis. They are also absent in denervated adrenals. These observations demonstrate that the increase in presynaptic acetylcholine levels produced by giving animals the neurotransmitter's precursor (choline) can be associated with parallel changes in the transmission of signals across cholinergic synapses, probably because more of the transmitter is released per nerve impulse.

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