Jacob L. Zaidman

ABETALIPOPROTEINEMIA TREATED WITH PARENTERAL AND ORAL VITAMINS A AND E, AND WITH MEDIUM CHAIN TRIGLYCERIDES

ABSTRACT. An 11‐year‐old girl with abetalipoproteinemia was treated with parenteral vitamin A and vitamin E for two and a half years. Some improvement in neurological and visual deficits was noted. On changing to oral vitamin E and later with addition of medium chain triglycerides (MCT) to the diet, a considerable improvement in her general wellbeing, neuromuscular lesions and ophthalmological symptoms was noted. This regimen is being adhered to for five and a half years. The condition is stable with no further improvement.

Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid

Changes in reduced glutathione (GSH) and pyridine nucleotide phosphate levels as well as in the activities of the glutathione peroxidase-reductase system and glucose-6-phosphate dehydrogenase have been studied in rats after a single i.p. administration of various doses of valproic acid (VPA). GSH level decreased in a dose-dependent relation. At the end of 180 min GSH levels either returned to control limits (lower doses) or showed a tendency to normalize (higher doses). GSH loss was paralleled by the reduction in glutathione reductase activity. A significant NADPH reduction was also seen after animal exposure to high VPA doses. At the end of 180 min a maximal NADPH decrease was reached. The activities of both glutathione peroxidase and glucose-6-phosphate dehydrogenase were suppressed irrespective of whether animals were given low or high VPA doses.

Neurophysiological and biochemical changes evoked by valproic acid in the central nervous system.

(1) Valproic acid is an anticonvulsant agent widely used in the management of various forms of epilepsy, including absence, myoclonic and tonic-clonic seizures. (2) It also has anticonvulsant potency in a wide variety of animal models of epilepsy. (3) This action is generally thought to be exerted through modulation of the activity of the endogenous inhibitory neurotransmitter, gamma-aminobutyric acid. (4) Evidence that valproic acid interacts with the gamma-aminobutyric acid system is presented. (5) Interactions of valproic acid with other neurotransmitters, i.e. aspartate, glutamate, taurine, serotonin, as well as with cyclic nucleotides and hormones are also considered. (6) Direct effects of valproic acid on excitable membranes and its relationships with analgesia are outlined.

Inhibition of human red blood cell glutathione reductase by valproic acid

Glutathione reductase (GR) one of the enzymes of the glutathione redox cycle, plays a salient role in maintaining appropriate cellular levels of reduced glutathione. The enzyme in human red blood cells is inhibited in vitro by the anticonvulsant drug valproic acid (VPA). The inhibition is dose-dependent, reversible, uncompetitive and does not depend on the redox state of the enzyme. VPA also inhibits red blood cell GR activity in children being treated with the drug. The level of serum VPA correlates significantly with the suppression of GR activity.

Studies on Urolithiasis in Israel

The composition of 1,000 kidney stones in our area of Israel was analyzed. The predominant stones were a combination of calcium oxalate and calcium phosphate, and uric acid. We used chemical analysis to determine the relative incidence of urinary calculi in 500 patients of various ages and ethnic groups. The incidence of calcium oxalate and calcium phosphate calculi (44 per cent) in Jews born in Israel was lower than in other ethnic groups (54 to 64 per cent). The incidence of uric acid stones in Jews born in Israel, Lebanon, Iran, Iraq and Syria, and the Ashkenazim (16 to 29 per cent) was 2 to 3 times higher than in other groups. In more than 60 per cent of the patients urolithiasis developed after they were 20 years old. The age at onset was significantly younger in Jews born in Israel (25.7 per cent) and North Africa (13.8 per cent), and in Arabs (18 per cent).

Effect of sodium valproate on subcellular fraction enzymes in rat liver.

Previous observations that valproic acid (VPA) causes hepatic damage prompted us to investigate the effect of large doses of the drug (0.6, 1.2 and 1.8 mmol/kg/day) on a number of liver enzymes located on different subcellular fractions. In mitochondria, glutamate dehydrogenase, aspartate aminotransferase and ornithine carbamoyltransferase were significantly increased (1.8 mmol/kg/day). In microsomes, gamma-glutamyltransferase activity increased significantly (1.8 mmol/kg) and cytochrome P-450 content decreased significantly (1.2 and 1.8 mmol/kg). In cytosol, both aspartate and alanine aminotransferase activities were increased at all dose levels. These results indicate that VPA induces dose-dependent changes in some liver enzyme activities.

Trends in urolithiasis in various ethnic groups and by age, in Israel

A survey of upper urinary tract stone composition was carried out over 8 years (1974-1982) in 1147 patients, following a previous survey (1966-1974). Trends in the development of stone formation were found. The most obvious differences were fewer pure calcium oxalate (0.75 versus 5.50%) and uric acid stones (6.11 versus 13.30%) and more mixed stones than in our previous study. In most ethnic groups urinary stones were composed of calcium oxalate/calcium phosphate. A higher prevalence of stones in Israeli-born Jews was noted, in comparison with our previous survey. Age group analysis showed this increase to be limited to the 21-50-year-old group, in contradistinction to a clear decrease in stone formation in Israeli-born Arabs and Jews under the age of 20 years.

On the heterogeneity of hemoglobin from normal and glucose-6-phosphate dehydrogenase-deficient individuals

Abstract Quantitative measurements of the different hemoglobin fractions obtained by CM-cellulose and Amberlite CG-50 chromatography and cellogel electrophoresis from normal and glucose-6-phosphate dehydrogenase-deficient adults are presented. The mean values, obtained by the three procedures, for the Hb-A 3 fraction of glucose-6-phosphate dehydrogenase-deucient red blood cells was lower than in normal red blood cells. (The difference was statistically significant in separations on CM-cellulose and cellogel electrophoresis). The mean values for the Hb-A 1 fraction, obtained by cellogel electrophoresis were significantly higher than m normal red blood cells. No significant difference in the amount of the Hb-A 2 fraction of the two kinds of red blood cells was observed. The significance of these results is discussed.

RIA examinations of CSF hormones as a method of demonstrating-leakage through the blood-brain and brain-CSF barriers

Radioimmunoassay determinations of the levels of total T3, total T4, TSH, and prolactin in the CSF were performed on samples taken from 36 healthy individuals. The obtained reference values are the first of their kind. It is considered that RIA determinations of CSF hormone levels may provide a sensitive method for demonstrating pathological leakage through the blood-brain and brain-CSF barriers.