Reduction in Brain Glucose Utilization Rate after Tryptophol (3-Indole Ethanol) Treatment

Abstract: 3-Indole ethanol has been recently identified as the hypnotic agent in trypanosomal sleeping sickness, and because it is formed in vivo after ethanol or disulfiram treatment, it is also associated with the study of alcoholism. When administered intraperitoneally to rats (250 mg/kg) tryptophol induced a sleep-like state that lasted less than an hour (no righting reflex was apparent 2 min after injection, but it returned at 11 min in bovine serum albumin solution, and 47 min in 40% ethanol solution). In ethanol solutions, tryptophol reduced brain cortical glucose utilization by 55% to the basal brain metabolic rate, and this effect lasted less than 1 h. Synergistic effects of tryptophol and ethanol were suggested by the observation that in albumin solution, tryptophol reduced brain glucose utilization by 35%, but a normal rate was not observed until 2 h postinjection.     

Age-related motor and catecholomine alterations in mice on levodopa supplemented diet

Old mice reared on regular diet show reduced motor activity, decreased basal adenylate cyclase, and increased MAO activities compared to adults. Brain DDC and COMT activities, DA, NE levels and DA-stimulated adenylate cyclase remained unchanged. By contrast, mice fed levodopa for life did not develop decreased motor activity with aging, lived about 50% longer, had slightly elevated whole brain DA and NE levels and failed to develop the expected rise in MAO activity with aging. Levodopa did not alter the number of dopaminergic and muscarinic cholinergic receptors or the adenylate cyclase activity in the striatum during aging. On levodopa, hepatic and renal DA, dopa, and HVA increased but the latter two returned to basal levels by mid life. In liver, DDC was unchanged but MAO tended to be higher in levodopa-fed mice. Thus, motor impairment is an age-related phenomenon in mice associated with selective alterations in brain dopaminergic systems, which may be prevented by dietary levodopa. Extracerebral tissues, through possibly adaptive metabolic mechanisms, play a significant role in regulating brain catecholamines during chronic administration of large doses of levodopa.     

DNA fork displacement rates in Bloom's syndrome fibroblasts

DNA fork displacement rates were measured in three lines of Bloom's syndrome cells and in a normal diploid fibroblast line. Fork displacement rates in Bloom's cells were approx. 55–65% of the rate in normal fibroblasts.     

Inborn errors of cobalamin metabolism: Effect of cobalamin supplementation in culture on methylmalonyl CoA mutase activity in normal and mutant human fibroblasts

We have examined the effect of addition of hydroxocobalamin to growth medium on the activity of the adenosylcobalamin-requiring enzyme methylmalonyl CoA mutase in normal human fibroblasts and in mutant human fibroblasts derived from patients with inherited methylmalonicacidemia. The mutant cell lines were assigned to four distinct genetic complementation groups (cbl A, cbl B, cbl C, and cbl D), each deficient in some step in the synthesis of adenosylcobalamin from hydroxocobalamin. After control cells were grown in cobalamin-supplemented medium, mutase holoenzyme activity increased markedly in a time- and concentration-dependent fashion. Growth in cobalamin-supplemented medium had no effect on mutase activity in some mutant lines belonging to the cbl B group, while activity increased severalfold in other cbl B mutants and in all cbl A, cbl C, and cbl D mutants examined, although mutase activity was still <10% of control. Comparison of mutase holoenzyme activity and total propionate pathway activity suggests that enhancement of mutase activity in mutant cells after cobalamin supplementation to values 5–10% of control may be sufficient to overcome the inherited metabolic block and to restore total pathway activity to normal.This work was supported in part by a research grant from the National Institutes of Health (AM 12579). H. F. W. is a recipient of a traineeship from the National Institutes of Health (T01-GM02299).     

A simple model for phase locking of biological oscillators

Summary A mathematical model is presented for phase locking of a biological oscillator to a sinusoidal stimulus. Analytical, numerical and topological considerations are used to discuss the patterns of phase locking as a function of the amplitude of the sinusoidal stimulus and the relative frequencies of the oscillator and the sinusoidal stimulus. The sorts of experimental data which are needed to make comparisons between theory and experiment are discussed.     

Cytochrome b5/cytochrome b5 reductase interaction in microsomes: kinetics at subzero temperature.

The cytochrome $\text{b}{}_5\text{b}{}_5$ reductase system solubilized from microsomes exhibits monophasic reduction kinetics over the temperature range 15 ° to ?25 °C in aqueous/ethylene glycol co-solvent, whereas in intact microsomes, the process becomes increasingly heterogeneous below 0 °C, reflecting heterogeneities in membrane structure observable as distributions in reaction rates and activation energies.     

The synergism of cardiotoxin and phospholipase A2 in hemolysis

The synergistic effect of exogenous cobra phospholipase A₂ on the hemolysis rate of guinea pig erythrocytes by highly purified snake venom cardiotoxins was investigated. In the presence of phospholipase A₂ the reaction was not only faster and had a lower activation energy but followed a sigmoidal instead of a linear time course. Similar results were obtained using porcine pancreatic phospholipase A₂. Significantly, addition of even a trace of cobra phospholipase A₂ (approx. 0.1%, w/w) was sufficient to bring about the full synergistic effect, emphasizing the stringent purity requirements for any meaningful investigation of cardiotoxin's own action. The possibility that the action of cardiotoxin on its own may involve the stimulation of an endogenous phospholipase is discussed in the light of the results obtained with exogenous cobra enzyme.     

Minimization of a sodium dithionite-derived interference in nitrate reductase-methyl viologen reactions

The use of sodium dithionite as the reducing agent to produce the radical cation of methyl viologen cofactor for the nitrate reductase-catalyzed reduction of nitrate to nitrite causes a negative interference in the diazonium salt azo dye determination of nitrite. The interference results from bisulfite, a reaction product of dithionite, reacting with the diazonium salt formed from nitrite and sulfanilamide. Addition of formaldehyde before the diazotization reaction masks this interference but at low acidity introduces a nonlinearity in the nitrite calibration curve. This nonlinearity is due to a competing reaction of formaldehyde with sulfanilamide to yield a Schiff base and can be eliminated by increasing the HCL content of the sulfanilamide reagent.     

Effect of antihistamines and chlorpromazine on the calcium-induced hyperpolarization of the Amphiuma red cell membrane

1. 1. It has previously been demonstrated that an increase in extracellular Ca²⁺ concentration induces a transient increase in K⁺ permeability and associated hyperpolarization of the red cell membrane of the giant salamander, Amphiuma means. This phenomenon is analogous to the Ca²⁺-induced KCl loss observed in ATP-depleted human red cells and red cell ghosts.

2. 2. Histamine, which enhances the Ca²⁺-induced K⁺ loss from depleted human red cells, is without effect on this Ca²⁺-induced hyperpolarization of Amphiuma red cells.

3. 3. Promethazine (10 μM) and mepyramine (1 mM), which inhibit the Ca²⁺-induced K⁺ loss in depleted human red cells, also block the Ca²⁺-related hyperpolarization of Amphiuma erythrocytes.

4. 4. Chlorpromazine (25 μM), despite being a weak antihistamine, is equally effective in blocking the Ca²⁺-induced hyperpolarization of Amphiuma red cells.

5. 5. Ionophore A23187 causes a large and sustained Ca²⁺/K⁺-dependent hyperpolarization even in the presence of normal (1.8 mM) concentrations of Ca²⁺. This hyperpolarization is relatively insensitive to chlorpromazine and promethazine.

6. 6. The inhibition of the Ca²⁺-induced hyperpolarization of the Amphiuma red cell membrane by chlorpromazine and promethazine may be related to their properties as local anaesthetics.

Changes during development in transport processes of the blood-brain barrier

The permeability of the blood-brain barrier to several classes of compounds was studied in rats between the ages of 15 days and 9 weeks. ¹⁴C-labelled test substances were injected simultaneously with two reference isotopes, ³H₂O and ^113mIn-labelled EDTA, into the common carotid artery followed by decapitation 10 s later.There was evidence that a monocarboxylic acid transport system in 15 to 23 day-old rats had a capacity at least six times greater than that present in adult animals. l-Lactate and acetate showed the highest permeability. At all ages there was a constant ratio between l-lactate and (−)d-3-hydroxybutyrate values. d-Glucose permeability increased with age, while that of several amino acids tested was the same in young and adults rats.