Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats with a portacaval anastomosis and ligation of the hepatic artery 2 days later were infused for 6 hr with a 10% glucose solution (group I) or the same solution combined with 0.24 M/liter branched-chain amino acids (BCAA, group II). Control animals with portacaval anastomosis and sham-operation (group III) or two sham-operations (group IV) were infused with a 10% glucose solution. The rats were killed by decapitation and indoleamines and amino acids were determined in the brain. Rats with liver ischemia were stuporous at the end of the experiment irrespective of treatment. The concentrations in the cortex of lysine, methionine, phenylalanine, threonine, alanine, glutamine, glycine, histidine, and tyrosine were significantly increased in group I compared to group IV. Infusion of BCAA to rats with liver-ischemia (group II) resulted in significantly lower concentrations of lysine, methionine, phenylalanine, threonine, histidine and tyrosine and increased concentrations of isoleucine, leucine, valine, and arginine compared to group I. The content of serotonin in the cortex and brain stem was significantly increased in group I compared with the BCAA-treated animals (group II) and the control groups III and IV. The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the cortex and brain stem were higher in group I than in group IV. Infusion of BCAA to rats with liver ischemia normalized the concentrations of 5-HIAA in the cortex and brain stem.
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PMID:Amino acids and indoleamines in the brain after infusion of branched-chain amino acids to rats with liver ischemia. 242 87

Medium-chain acyl-CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium-chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium-chain acyl-CoA dehydrogenase deficiency. We report the results of carefully monitored fasting challenges of an infant with this deficiency both before and after 3 months of oral carnitine therapy. Carnitine supplementation failed to prevent lethargy, vomiting, hypoglycaemia and accumulation of free fatty acids in response to fasting despite normalization of plasma carnitine levels and a marked increase in urinary excretion of acyl-carnitine esters. Potentially toxic medium-chain fatty acids accumulated in the plasma in spite of therapy. Based on this study of one patient, we stress that avoidance of fasting and prompt institution of glucose supplementation in situations when oral intake is interrupted remain the mainstays of therapy for medium-chain acyl-CoA dehydrogenase deficient patients.
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PMID:Medium-chain acyl-CoA dehydrogenase deficiency: metabolic effects and therapeutic efficacy of long-term L-carnitine supplementation. 250 71

Although the conditions that cause hypoglycemia in adults may also be present in infants and children, there are many entities unique to the pediatric age group. This reflects the delicate balance that exists in the newborn and young child between glucose production and utilization. During fasting in infants and children, hepatic glucose production is normally two to three times that of adults when expressed on the basis of weight. In the newborn and young infants, hypoglycemia usually presents with irritability, feeding difficulties, lethargy, cyanosis, tachypnea, and/or hypothermia rather than the typical adrenergic or neuroglucopenic symptoms seen in the adult. The hypoglycemia may be due to abnormalities in hormone secretion, substrate interconversion, or mobilization of metabolic fuels. The hypoglycemia associated with hyperinsulinemia may be transient neonatal, sustained, or drug-induced. Inborn errors of metabolism caused by enzymatic defects are responsible for hypoglycemia associated with abnormalities of production and utilization of metabolic fuels. These can involve carbohydrate, protein, and fat metabolism. In addition, there may be acquired or transient defects in carbohydrate metabolism secondary to other diseases or ingestion of certain substances. Finally ketotic hypoglycemia appears to be due to abnormalities in substrate availability. A variety of tests are useful for establishing the etiologic basis of the hypoglycemia, and the appropriate treatment depends upon the underlying cause.
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PMID:Hypoglycemia in infants and children. 264 28

Plasma glucose and glucagon concentrations were measured in edible dormice during the bout of hibernation, arousal and active periods. During lethargy, plasma glucose and glucagon were low, compared to active values and did not fluctuate throughout the phase. During rewarming, plasma glucose regularly increased from 17 degrees to 37 degrees C while plasma glucagon rose after the 17 degrees C stage and reached the higher values at 26 degrees C, then slightly decreased at 37 degrees C. During arousal, plasma levels of free amino acids progressively increased. The effect of temperature and secretagogue (glucose and arginine) on glucagon secretion was studied using perfused pancreas from hibernating edible dormouse. In vitro rewarming of pancreas induced an increase in glucagon secretion. Glucagon secretion was regulated by glucose (inhibitory effect) and by arginine (stimulating effect) up to 25 degrees C. The effect of temperature and glucagon on oxygen uptake of hibernating edible dormouse brown fat was studied using an in vitro technique. Rewarming strongly increased oxygen consumption from 10 to 37 degrees C. Glucagon enhanced oxygen consumption up to 20 degrees C.
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PMID:Glucagon secretion in the hibernating edible dormouse (Glis glis). 286 68

A 19-mo-old boy with cystic fibrosis presented with a lifelong history of feeding problems and constipation, and an 8-mo history of episodes of repeated retching, diaphoresis, dehydration, and somnolence after eating. Tests of esophageal motility and gastric emptying of a 5% glucose meal were normal. Antroduodenal pressure recordings during fasting demonstrated the presence of all phases of the interdigestive motor complex. After consumption of a 240-ml complex liquid meal, however, the contractile pattern that generally accompanies eating was absent and gastric emptying was markedly delayed. When bethanechol or metoclopramide was given 10 min before the complex liquid meal, there was a paucity of contractile activity, gastric emptying was slow, and symptoms of lethargy, diaphoresis, and retching were present. When cisapride was given, there was frequent irregular contractile activity, faster gastric emptying, and no symptoms of lethargy. During the past year treatment with cisapride has been a requirement in order to prevent recurrence of the symptoms. Antroduodenal pressure studies proved helpful in the identification of a treatable manometric abnormality that was associated with symptoms of delayed gastric emptying.
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PMID:Absent postprandial duodenal motility in a child with cystic fibrosis. Correction of the symptoms and manometric abnormality with cisapride. 287 3

We report a 5-month-old boy with recurrent vomiting, lethargy, and poor weight gain. He had profound metabolic acidosis and nonketotic dicarboxylic aciduria. The serum and muscle carnitine levels were significantly low (60% and 10% of the control means, respectively), suggesting that the patient had a systemic carnitine deficiency syndrome. The patient showed apparent clinical improvement on oral carnitine administration. A quadriceps muscle biopsy revealed a slight increase in intrafiber lipid droplets and mild accumulation of glycogen in the subsarcolemmal portion. An anaerobic glycolysis in vitro study showed a block after glucose-1-phosphate and before glucose-6-phosphate. Direct measurement of individual glycolytic enzymes in muscle of the patient demonstrated a marked decrease in phosphoglucomutase (PGM) activity (13% of the control mean). The specific defect of PGM activity in this patient suggests that the block in the anaerobic glycolytic pathway is the primary abnormality. PGM deficiency can be added as a newly recognized cause of secondary systemic carnitine deficiency syndromes.
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PMID:Infantile muscle glycogen storage disease: phosphoglucomutase deficiency with decreased muscle and serum carnitine levels. 296 17

Symptomatic hypoglycemia developed 5 to 45 months after transplantation in nine children who had renal transplants before 6 years of age. During hypoglycemia, serum glucose levels ranged from 14 to 39 mg/dl (0.8 to 2.1 mmol/L). Hypoglycemic episodes occurred between 1.7 and 7.5 years of age. Six patients had generalized seizures; the remaining three had diaphoresis with stupor or lethargy. None of the children had serious infections, diabetes, congenital defects of glucose metabolism, or a history of treatment with insulin or oral hypoglycemic agents. Six patients had hypoglycemic symptoms after a prolonged fast, and at least four had ketosis. Eight of the nine patients were receiving propranolol when hypoglycemia occurred. No differences in the daily prednisone dose, the number of transplant rejection episodes, or the frequency of treatment with medications other than propranolol were noted between hypoglycemic patients and 56 normoglycemic age-matched renal transplant recipients. All hypoglycemic patients were subsequently treated with frequent feedings and discontinuation of propranolol. No further hypoglycemic episodes have occurred in eight of nine patients. Symptomatic hypoglycemia should be recognized as a potentially devastating complication of pediatric renal transplantation.
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PMID:Hypoglycemia in pediatric renal allograft recipients. 305 55

In winter, hibernating mammals enter a long phase of lethargy which is characterized by low body temperature, depressed metabolism and minimal release of metabolic substrates from endogenous fuel stores. Periodically, they spontaneously warm themselves to regain the euthermic state. These arousals are, by contrast, times of high release and consumption of endogenous substrates. Insulin and glucagon may contribute to the control of both contrasting metabolic periods. The secretion and metabolic effects of these two hormones were investigated in two hibernators: the hedgehog (Erinaceus europaeus) and the edible dormouse (Glis glis). During lethargy, blood glucose, insulin and glucagon concentrations were low. In vivo and in vitro studies showed that the secretion of both hormones was markedly depressed by low temperatures. Insulin secretion was not stimulated by glucose, although glucagon secretion remained reactive to arginine. Blood glucose was not regulated by insulin but pharmacological doses of glucagon increased blood glucose concentrations. The tissues were found to be highly insulin-resistant, preventing the fall of blood glucose and consequently limiting the depletion of glucidic substrates during the long periods of starvation. During arousal, blood glucose, insulin and glucagon levels increased at the end of rewarming while glucose turnover gradually increased above a body temperature of 15 degrees C. The effects of glucagon and insulin on glucose metabolism increased markedly beyond this stage. Thus the metabolic effect of both hormones are temperature-dependent. Insulin and glucagon allow an increase in glucose availability for the active metabolic processes which occur during arousal.
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PMID:[Regulation of endocrine pancreas secretions (insulin and glucagon) during the periodic lethargy-waking cycle of the hibernating mammal]. 330 41

1. At 30 weeks of age, homozygote diabetic C57 BL KsJ (db/db) mice were grossly obese, lethargic and displayed moderate hair loss relative to heterozygote control C 57 BL KsJ (db/+) mice. 2. In diabetic mice, compared to control, the total body weights, liver weight: body weight ratios, and blood glucose levels were increased 2.3 fold, 20% and 3.1 fold, respectively. 3. Analysis of plasma membranes isolated from control and diabetic mouse liver established that comparable purity levels were achieved since relative specific activities of the plasma membrane markers 5'-nucleotidase and gamma-glutamyltranspeptidase were similar: 10.2 and 11.4 fold with respect to 5'-nucleotidase in control and diabetic states respectively; and 8.0 and 8.3 fold with respect to gamma-glutamyltranspeptidase in control and diabetic states respectively. 4. A select effect of diabetes on gamma-glutamyltranspepetidase, however, was observed. The activity of this enzyme was found to be reduced 16% in diabetic liver compared to control liver. 5. Assessment of [3H]prazosin and [3H]dihydrolalprenolol binding to mouse liver plasma membranes indicated that although there was no difference in beta-adrenergic receptor binding in control and diabetic states, alpha 1-adrenergic receptor binding was found to be reduced 43% in diabetic mouse liver plasma membranes. 6. Scatchard analyses of kinetic studies indicate that the reduction is a reflection of decreases in alpha 1-adrenergic receptor numbers with no change in alpha 1 receptor affinity in the diabetic state: since for diabetic and control liver plasma membranes, Kd values were 3.41 +/- 0.02 nM and 3.40 +/- 0.01 nM respectively; and Bmax were 650.12 +/- 16.44 fmol mg-1 and 380.76 +/- 12.92 fmol mg-1, respectively.
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PMID:Hepatic adrenergic receptors in the genetically diabetic C57 BL/KsJ (db/db) mouse. 343 80

T-2 toxin at 0 (6 pigs) or 15 mg/kg (8 pigs) in 0.75 ml of dimethyl sulfoxide was topically applied to 9- to 10-week-old, male castrated, specific-pathogen-free derived pigs which were immunized subcutaneously with sheep red blood cells (SRBC) on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic evaluations. The pigs were observed daily and weighed weekly; their rectal temperatures were measured periodically. The T-2-treated pigs displayed anorexia, lethargy, posterior weakness and paresis, persistent high fever, and reduced body weight gain. Prominent neutrophilia, decreased serum glucose, albumin, and alkaline phosphatase activity, and increased serum globulin were seen in the T-2-treated group. The responses of enriched peripheral blood mononuclear cells to mitogens concanavalin A, phytohemagglutinin, and pokeweed mitogen of the T-2-treated group were significantly lower than those of the control group both at early (3 to 5 days) and late (20 to 28 days) postdosing intervals. No significant effects were noted in the hemagglutination titer to SRBC. Thus, in addition to the severe local dermal injury reported previously, topical exposure of swine to a sublethal dose of T-2 toxin, 15 mg/kg, can cause significant systemic effects on parameters such as body weight gain, rectal temperature, hematology, serum biochemistry, and cellular immune response.
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PMID:The toxicity of T-2 toxin in swine following topical application. II. Effects on hematology, serum biochemistry, and immune response. 362 63


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