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Biomedical subjects

A E Slonim

Publications and source records attributed to A E Slonim.

At least 37 records · Page 2Linked to original sources
PubMed1984

Myopathy and growth failure in debrancher enzyme deficiency: improvement with high-protein nocturnal enteral therapy.

Seven patients with debrancher enzyme deficiency and childhood or adolescent onset myopathy, four of whom also had growth failure, received long-term treatment consisting of high-protein enteral infusion overnight and high-protein feeds during the day for periods varying from 8 to 42 months. All patients demonstrated improvement in physical activity and endurance. Improvement in muscle strength was documented in five patients, with reversal of myopathic EMG patterns to normal in two patients and reversal of abnormal ECG findings to normal in one patient. All four patients with growth failure showed dramatic improvement in growth rates. This positive response to high-protein enteral therapy supports the concept that myopathy in debrancher enzyme deficiency is at least partly the result of reversible muscle amino acid depletion.

Adolescent↗
PubMed1984

Chemiluminescence as an index of drug-induced free radical production in pancreatic islets.

Chemiluminescence induced in isolated islets from rat pancreas by the diabetogenic drugs, alloxan and streptozotocin, has been measured. The assay system consisted of 3 microM of luminol, 10 islets, and 100 microM of alloxan or 500 microM of streptozotocin in 5 ml Krebs-Ringer bicarbonate buffer containing 16 mM of Hepes (pH 7.4). Alloxan-induced chemiluminescence appeared very rapidly and lasted more than 5 min. On the other hand, streptozotocin failed to produce chemiluminescence over a period of 60 min after addition. The presence of superoxide dismutase (1000 U/ml) and/or catalase (100 U/ml) markedly suppressed alloxan-induced chemiluminescence. These results suggest that alloxan acts as an exogenous free radical generator in pancreatic islets, but that streptozotocin does not. The involvement of superoxide anion and hydrogen peroxide in production of chemiluminescence by alloxan suggests that the hydroxyl radical may mediate this chemiluminescence.

Alloxan↗
PubMed1984

Recurrent Reye-like syndrome: possible association with Krebs cycle abnormality.

During a 7-year period, a 15-year-old boy experienced recurrent attacks that clinically and pathologically resembled Reye's syndrome. The attacks were precipitated by prolonged exercise, fasting or infections. An extensive investigation failed to identify a toxic cause or specific metabolic disorder. Low 14CO2 production after in vitro incubation of the patient's liver with 14C-labeled palmitate, citrate and glutamine suggested a defect in the Krebs cycle or the oxidative phosphorylation pathway. This error may be responsible for the recurrent Reye-like syndrome attacks.

Adolescent↗
PubMed1983

Amino acid disturbances in type III glycogenosis: differences from type I glycogenosis.

The plasma glucose, insulin, glucagon, lactate and amino acid response patterns to glucose and protein meals were examined in 11 patients with type III glycogen storage disease (GSD-III). The amino acid metabolism in GSD-III was shown to differ from that observed in normal subjects and in type I glycogen storage disease (GSD-I) patients. The outstanding findings involved the principal gluconeogenic amino acid, alanine. Postabsorptive levels of alanine in GSD-III were significantly below those of normal controls. Following glucose ingestion, alanine rose markedly in GSD-III, which differed from normal subjects in whom no change occurred, and from GSD-I patients in whom a sharp fall was observed. Following beef ingestion, the direction of change of alanine was similar in the three groups, but the circulating levels in GSD-III were significantly less than those observed in GSD-I and normal controls. The possibility that gluconeogenesis is enhanced in GSD-III was supported by the prompt rise in blood glucose observed following beef ingestion, which differed from GSD-I and normal subjects, in which no rise in glucose was observed.

Adolescent↗
PubMed1983

Modification of chemically induced diabetes in rats by vitamin E. Supplementation minimizes and depletion enhances development of diabetes.

Administration of the antioxidant vitamin E to rats, prior to administration of either streptozotocin or alloxan, provided protection against the diabetogenic effect of both these agents. This was demonstrated by their response to a glucose load, their pancreatic insulin content and light microscopy findings. In addition, rats whose antioxidant state was depleted, by being maintained on a vitamin E and selenium-deficient diet, demonstrated increased diabetogenic susceptibility to normally nondiabetogenic doses of streptozotocin. These findings provide indirect support for the suggestion that the chemical agents streptozotocin and alloxan may exert their diabetogenic effect by acting as oxidants or free radical producers.

Alloxan↗
PubMed1983

Nonketotic hypoglycemia: an early indicator of systemic carnitine deficiency.

In systemic carnitine deficiency, an early phase of nonketotic hypoglycemia and liver dysfunction may precede a late phase of encephalopathy and myopathy. We studied two children with recurrent episodes of nonketotic hypoglycemia who were found to have systemic carnitine deficiency without myopathy or encephalopathy. Early institution of appropriate therapy prevented the onset of late debilitating complications in one patient, whereas therapeutic noncompliance in the other patient led to an episode of encephalopathy and myopathy. Metabolic studies indicated that decreased availability of alanine may be a factor in the genesis of hypoglycemia; concurrent depletion of cerebral glucose, ketones, and glycogen may be the cause of the encephalopathy.

Brain Diseases↗
PubMed1983

Improvement of muscle function in acid maltase deficiency by high-protein therapy.

Progressive muscle weakness in acid maltase deficiency (AMD) is associated with intralysosomal accumulation of glycogen and altered myofibrillar morphology. A rapid fall in circulating branched chain amino acids after protein ingestion in a child with AMD suggested that increased net muscle protein catabolism may play a part in the pathogenesis of this condition. To reduce this muscle catabolism, the patient was treated with a high-protein diet for 12 months. This has reversed the weakness and wasting, with improvement in muscle function, exercise tolerance, and growth.

Amino Acids, Branched-Chain↗
PubMed1982

Reversal of debrancher deficiency myopathy by the use of high-protein nutrition.

A child with debrancher deficiency presented with myopathy, recurrent hypoglycemia, and growth failure. Evidence for enhanced gluconeogenesis was demonstrated by low postabsorptive gluconeogenic plasma amino acids, a marked fall in alanine during fasting, and a substantial rise in plasma glucose following protein ingestion. The patient was treated with high-protein nocturnal intragastric therapy, which resulted in marked improvement in exercise tolerance, muscle strength and mass, electromyographic findings, and growth.

Amino Acids↗
PubMed1982

Cholesterol reduction by a high-glucose diet in a patient with homozygous familial hypercholesterolemia. A preliminary report.

Homozygous familial hypercholesterolemia is refractory to standard dietary or drug therapy. Recent studies, however, suggest that a high-carbohydrate/low-fat diet may reduce circulation cholesterol levels in normal or hyperlipidemic subjects. In this regard, we treated a nine year old boy with homozygous familial hypercholesterolemia with a liquid formula diet containing 82 to 90 percent of total calories as glucose. The diet was given as a constant nasogastric infusion or as intermittent daytime drinks followed by a nighttime infusion. Plasma total and low-density lipoprotein cholesterol fell from basal levels of 719 mg/dl and 676 mg/dl to 456 mg/dl and 434 mg/dl, respectively, after one week of therapy. After approximately 14 weeks of treatment, plasma total and low-density lipoprotein cholesterol levels were 311 mg/dl and 277 mg/dl, each representing approximately a 58 percent decrease from basal levels. The fall in circulating cholesterol levels was accompanied by a regression of xanthomatous skin lesions, a rise in plasma insulin levels and no change in plasma glucose or glucagon concentrations. No adverse effects of therapy occurred. We conclude that high-carbohydrate diets may be a safe and effective adjunct in the treatment of homozygous familial hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1981

Dietary-dependent carnitine deficiency as a cause of nonketotic hypoglycemia in an infant.

Recurrent episodes of hypoglycemia, prostration, vomiting, and hepatomegaly were observed in an infant fed a carnitine-free soy formula. The extremely low plasma and urinary carnitine concentrations, elevated plasma free fatty acids, disproportionately low plasma beta hydroxybutyrate, and elevated urinary dicarboxylic acids, in the presence of a fatty liver, suggested that carnitine deficiency was the basis for this child's metabolic disturbance. When the infant was fed an enriched carnitine diet, remarkable clinical, biochemical, and histologic improvement was observed. The possibility that carnitine may be an essential nutrient for some infants is raised by the findings in this patient.

Carnitine↗
PubMed1981

Elevated cholesterol and bile acid synthesis in an adult patient with homozygous familial hypercholesterolemia. Reduction by a high glucose diet.

Elevated levels of cholesterol synthesis are reported for several young children with homozygous familial hypercholesterolemia (HFH) and are considered to contribute directly to their hypercholesterolemia. In contrast, increased cholesterol production has not previously been found in adult patients with HFH. Using the fecal steroid balance technique, we studied rates of cholesterol and bile acid synthesis in a 24-yr-old man who had severe hypercholesterolemia typical of HFH and who lacked skin fibroblast low density lipoprotein (LDL) receptor activity. On an average diet (45% carbohydrate, 40% fat, 15% protein) mean +/- SEM cholesterol (24.8 +/- 1.4 mg/kg per d) and bile acid (11.1 +/- 1.6 mg/kg per d) excretion were approximately threefold higher than normal. When an isocaloric high carbohydrate, low fat diet (90.5% glucose oligosaccharides, 1.3% safflower oil, 8.2% crystalline amino acids was substituted, mean cholesterol (13.0 +/- 0.5 mg/kg per d) and bile acid (8.6 +/- 0.4 mg/kg per d) fell markedly. The decline in fecal steroid excretion was accompanied by modest reductions in plasma total and LDL cholesterol concentrations and by a softening of cutaneous xanthomata. Although the patient phenotypically and biochemically resembled the HFH state, his family pedigree was not noteable for hypercholesterolemia. While the patient's father had premature cardiovascular disease, his mother had no evidence of heart disease, had normal plasma total and LDL cholesterol levels, and had normal fibroblast LDL receptor activity. Likewise, the plasma cholesterol levels of three other members of the patient's family were normal. Despite the unusual genotypic background of this individual, however, the fecal balance data shows that elevated cholesterol and bile acid synthesis may occur in adult, as well as juvenile, patients with HFH and may be responsive to dietary control.

Adult↗
PubMed1980

Protection against streptozotocin-induced diabetes by superoxide dismutase.

Suerpoxide dismutase was administered intravenously to rats 50 min prior to intravenous administration of a diabetogenic dose of streptozotocin. A dose of 45 mg/kg streptozotocin alone produced marked glucose intolerance and a decrease in pancreatic insulin content to less than 10% of control; both of these effects were abolished by prior administration of 105 mu/g of superoxide dismutase. Superoxide dismutase (105 mu/g) administered 50 min before 65 mg/kg intravenous streptozotocin did not prevent the development of diabetes. The fall in pancreatic insulin content seen with streptozotocin alone was, however, partially reversed by superoxide dismutase.

Animals↗
PubMed1980

Type I glycogen storage disease: five years of management with nocturnal intragastric feeding.

It has been five years since the original report indicating that intragastric feedings could reverse most of the clinical and metabolic abnormalities present in patients with type I glycogen storage disease. We have now treated seven patients with nocturnal intragastric feedings for five years. All patients have shown marked improvement in blood chemical values (urate, lactate, triglyceride, cholesterol) as well as linear growth. The only serious complication has been symptomatic hypoglycemia and acidosis resulting from acute gastroenteritis and vomiting. Results indicate that nocturnal intragastric feeding is a practical, safe, and effective form of long-term treatment for patients with type I glycogen storage disease.

Child, Preschool↗
PubMed1980

Regulatory role of glutathione and soluble sulfhydryl groups in the toxicity of adriamycin.

Adriamycin (ADR) has been shown to produce free radicals in NADPH microsomal systems, to increase oxygen consumption of both hepatic microsomes and heart sarcosomes and to stimulate superoxide formation in cardiac, submitochondria particles. These reactive products could produce the cardiotoxicity of ADR by oxidizing various membrane structures, especially if the heart lacks sufficient protective reducing substances such as thiols. We examined 1) the effect of ADR on reduced glutathione (G-SH) levels in various tissues including heart, 2) the ability of the sulfhydryl (SH) donor, cysteamine, to alter soluble SH levels in heart tissue after ADR administration and 3) the effects of SH donors (cysteamine and N-acetyl cysteine and G-SH depletion by diethyl maleate on ADR-induced lethality in Swiss ICR-HA mice. A single injection of ADR (15 mg/kg i.p.) elicited a statistically significant fall in liver (P < .05), heart (P < .02) and erythrocyte (P < .01) G-SH levels. Treatment with cysteamine protected against the fall in soluble SH groups in heart tissue. Cysteamine (50 mg/kg, i.p., every 8 hr for 6 days) or N-acetylcysteine (100 mg/kg, i.p., 1 hr before and 7 hr after ADR) protected against ADR-induced lethality and decreased the appearance of microscopic myocardial lesions. When endogenous levels of G-SH were depleted by diethyl maleate (300 mg/kg i.p., every 8 hr for 4 days), ADR lethality was markedly potentiated. Diethyl maleate alone did not cause death. We conclude 1) ADR significantly lowers G-SH levels in erythrocytes, liver and heart tissue, 2) the lowering of cardiac SH groups by ADR can be prevented by cysteamine and 3) ADR toxicity can be potentiated by diethyl maleate, a G-SH depletor, and reduced by cysteamine or N-acetyl cysteine, SH donors. These results suggest that the G-SH system may be involved in the modulation of ADR-induced toxicity.

Animals↗
PubMed1979

Nocturnal intragastric therapy in type I glycogen storage disease: effect on hormonal and amino acid metabolism.

The acute hormonal and amino acid responses to differing food substrates were examined in type 1 glycogen storage disease. Ingestion of a glucose load or a glucose-plus-beef meal caused an acute fall in the initially elevated plasma glucagon, alanine, proline, and lactate. Ingestion of beef alone caused a sharp rise in these parameters. Long term nocturnal intragastric therapy of a high carbohydrate and moderate amino acid content resulted in a similar fall in these parameters as well as a fall in the elevated plasma glutamate, uric acid, triglycerides, and RBC-reduced glutathione. A remarkable clinical improvement and growth spurt accompanied the improvement in these biochemical values. The possible relation between the disturbed plasma hormonal and amino acid findings and growth failure and hyperuricemia is discussed.

Adolescent↗