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Biomedical subjects

A E Slonim

Publications and source records attributed to A E Slonim.

48 records · Page 3Linked to original sources
PubMed1978

ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I.

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.

Adenosine Triphosphate↗
PubMed1976

Continuous nocturnal intragastric feeding for management of type 1 glycogen-storage disease.

The clinical and biochemical abnormalities associated with Type 1 glycogen-storage disease can be reversed by avoidance of hypoglycemia and secondary hormonal flux. Three patients with Type 1 disease were treated with intragastric infusions of a high glucose formula at night with three-hour starch feedings during the day. This regimen stabilized blood glucose levels above 70 mg per deciliter and decreased serum uric acid, triglyceride, lactate and serum oxalacetic transaminase levels, as well as hepatic size, in all patients. Increased linear growth rate (mean 1 cm per month) was associated with a decrease in mean plasma glucagon (from 190 to 40 pg per milliliter) and an increase in mean plasma insulin (from 19 to 43 muU per milliliter, [two patients]). These changes occurred within four weeks of beginning of treatment and continued with home treatment for 13 months. No complications resulted from tube placement daily by the patients. Type 1 disease can be managed by nighttime intragastric feeding and frequent daytime high starch meals.

Adolescent↗
PubMed1976

Diencephalic syndrome revisited.

This report details the histories of five patients with clinical diencephalic syndrome who collectively demonstrate the variability found in the syndrome with respect to: (1) clinical course, (2) site of the tumor, and (3) ease of obtaining radiologic confirmation of the presence of a tumor. A review of an additional 67 patients indicates that the observations are not unique. The anatomic variability combined with the fact that the course of those who are treated is infinitely better than those left untreated adds urgency to the establishment of precise anatomic diagnosis. These considerations led to a critical review of the histories of the 72 patients. From this it can be stated that anteriorly and posteriorly placed tumors do exhibit subtle but significant differences in their clinical course, and roentgenograms of the optic foramina and analysis of the CSF cell and protein content appear warranted early in the investigation of emaciation from unknown cause. Further, an evaluation is made of the role of various radiologic techniques and of endocrine studies in establishing the diagnosis. Similarly, the relative merits of radiotherapy and/or surgery in the treatment of the disease are defined. Finally, the adequacy of the term diencephalic syndrome is discussed.

Astrocytoma↗
PubMed1976

Extracellular calcium and adrenergic and cholinergic effects on islet beta-cell function.

An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.

Acetylcholine↗
PubMed1976

Interactions of acetylcholine and epinephrine on the dynamics of insulin release in vitro.

An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of epinephrine on acetylcholine-induced insulin release over varying concentrations of the two agents. Perifusion of islets with epinephrine before challenge with acetycholine produced marked enhancement of both phases of cholinergically induced insulin release; enhancement of the first phase being more marked with increase in acetylcholine concentration and the converse being observed with the second phase. Perifusion of islets with epinephrine during stimulation with acetylcholine produced inhibition of insulin release, an effect dependent upon the concentration of epinephrine and of acetylcholine. There was an order of difference in the acetycholine concentration needed to overcome significant epinephrine-mediated inhibition of the first phase of insulin release (5 X 10(-4) mug/ml) and that needed to overcome inhibition of the second phase (5 X 10(-3) mug/ml). Comparison of the effects of various concentrations of epinephrine on glucose- and acetyl-choline-induced insulin release revealed that epinephrine was a less potent inhibitor of the first phase of acetylcholine-induced insulin release than of the first phase of glucose-induced insulin release. These data provide some insight into the potential interactions between cholinergic and adrenergic autonomic systems in modifying insulin release.

Acetylcholine↗
PubMed1976

Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine.

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.

Animals↗
PubMedDate not supplied

Early onset of diabetes mellitus associated with the mitochondrial DNA T14709C point mutation: patient report and literature review.

We report a family in which a mother and son were affected with diabetes mellitus and myopathy characterized by ragged red fibers and suggestive of mitochondrial disease. Mitochondrial DNA (mtDNA) analysis of DNA isolated from peripheral blood showed a T-->C point mutation at nucleotide position 14709, in the transfer RNA gene for glutamic acid. We review the association of diabetes and mtDNA mutations. This child's case is unusual because of the early onset of diabetes, which is more typical of mtDNA deletions.

Adult↗
PubMedDate not supplied

Evaluation of the lumbar spine in patients with glycogen storage disease: CT demonstration of patterns of paraspinal muscle atrophy.

CT studies of the lumbar spine were performed in 19 patients with glycogen storage disease. Nine of 10 patients with McArdle's disease and seven of nine patients with acid maltase deficiency demonstrated posterior paraspinal muscle atrophy out of proportion to their ages. In addition, the psoas muscles were spared in all 10 patients with McArdle's disease and were involved with atrophy in seven of the nine patients with acid maltase deficiency. We conclude that when patients with low back pain-or asymptomatic patients-demonstrate otherwise unexplained atrophy of the paraspinal muscles the diagnosis of glycogen storage disease should be considered. Furthermore, when the psoas muscles are spared, the specific diagnosis of McArdle's disease is suggested.

Adipose Tissue↗