Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic disturbances in glucose-6-phosphatase deficiency (von Gierke's disease) are the consequence of hypoglycemia, occurring mostly during the night. Continuous provision of glucose is the aim of every recently introduced treatment procedure. We studied the influence of continuous ambulatory peritoneal dialysis (CAPD) on the metabolic disturbances in a 42-year-old female patient with von Gierke's disease and end-stage renal disease. During six months of CAPD, there were no dialysis-related complications. The metabolic acidosis didn't worsen: arterial bicarbonate and lactate were not changed. Mean glycemia was 118.6 +/- 14.4 mg%. Total lipemia, cholesterol and triglycerides were not different from those before CAPD, despite the fact that all hypolipidaemic drugs were stopped. Three different exchange procedures were compared during the night: no dialysis, one exchange with a 2 L solution without buffer containing glucose 15 g/L and containing glucose 42.5 g/L. The results show that the 4.25% glucose solution prevents hypoglycaemia, and diminishes the increase in lactate and pyruvate concentration. Intraperitoneal glucose normalizes the plasma free fatty acid concentration. A very important result is the disappearance of hypo-insulinism. We conclude that, from a clinical point of view, CAPD is a well-tolerated treatment in von Gierke's disease. The limited results provide some evidence that the use of a 4.25% glucose solution as an overnight exchange, instead of the usual 1.5% solution, can prevent at least partly the glycogenolysis and consequently the metabolic disturbances of von Gierke's disease.
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PMID:Continuous ambulatory peritoneal dialysis (CAPD) in a patient with glucose-6-phosphatase deficiency. 248 95

As is obvious from the previous discussions, obesity is associated with a wide variety of changes in endocrine parameters (Table 1). Some of these changes, such as the reduction in SHBG without change in serum free testosterone levels, reflect merely laboratory abnormalities that may influence interpretation of diagnostic tests but have no important physiologic relevance. Other abnormalities have major clinical impact, such as hyperestrogenemia-endometrial carcinoma and hyperlipidemia-coronary artery disease. In some cases, endocrine changes in obesity are beneficial--that is, hyperestrogenemia leading to lower incidence of osteoporosis. In other cases, such as the profound suppression of growth hormone output in obesity, the physiologic relevance is unknown. Several endocrine changes in obesity, such as the impaired response of many hormones (growth hormone, prolactin, vasopressin, corticotropin) to insulin-induced hypoglycemia and elevated endorphin levels, suggest hypothalamic dysfunction. Furthermore, the failure of all of these abnormalities to be normalized after weight reduction raises the possibility of an underlying disorder leading to both endocrine dysfunction and obesity, rather than the endocrine dysfunction being simply a consequence of the obesity. Successful elucidation of the pathogenesis of obesity, which might then lead to much needed specific treatment modalities, may be advanced if we can solve some of these puzzles.
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PMID:Endocrine aspects of obesity. 264 1

Salmon (Oncorhynchus kisutch) somatostatin (sSS; 4 or 8 ng/g body wt) or synthetic Gillichthys urotensin II (UII; 2 or 4 ng/g body wt) were injected intraperitoneally into juvenile freshwater coho salmon. Both sSS and UII caused a dose-dependent increase in plasma free fatty acids (FFA) which diminished with time. sSS induced an initial (1 hr) transient hyperglycemia. By contrast, UII tended to induce hypoglycemia, this effect being significant 5 hr after injection of the higher dose. Both sSS and UII depressed plasma insulin titers 1 hr after injection. By 3 hr, the sSS-associated insulin depression was no longer observed. UII treatment induced a hyperinsulinemia which was present 3 and 5 hr after peptide administration. Although no decreases in liver total lipid concentration or in mesenteric fat total tissue mass were observed, lipolytic enzyme activity within each depot was significantly enhanced by both peptides. Neither sSS nor UII altered 3H2O incorporation into fatty acids or neutral lipids. However, enhanced lipogenesis, particularly by UII, was indicated by increased NADPH production resulting from glucose-6-phosphate dehydrogenase activity. Both sSS and UII enhanced glucose mobilization, as indicated by decreased liver glycogen content and increased liver glucose-6-phosphatase activity. UII, but not sSS, stimulated glycogen synthetase activity. These results suggest that both sSS and UII stimulate hyperlipidemia by enhancing depot lipase activity and that although both factors are potentially gluconeogenetic, sSS seems to be glycogenolytic and hyperglycemic, whereas UII may channel glucose to FFA synthesis.
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PMID:Effects of somatostatin-25 and urotensin II on lipid and carbohydrate metabolism of coho salmon, Oncorhynchus kisutch. 288 97

Carnitine facilitates the transport of activated fatty acids across the mitochondrial membrane and regulates energy metabolism through regeneration of intramitochondrial coenzyme A. In carnitine deficiency it may be a limiting factor for fatty acid oxidation and ketogenesis. Primary myopathic carnitine deficiency is characterized by low carnitine concentrations usually restricted to muscle; whereas systemic carnitine deficiency shows decreased concentrations in other organs and plasma as well. The latter condition features recurrent metabolic crises similar to those seen in Reye's syndrome and nonketotic hypoglycemia. A therapy with L-carnitine should be undertaken, but does not always prove effective. Similar symptoms may be caused by defects in beta-oxidation, Krebs cycle or respiratory chain enzymes. The conditions may be associated with secondary carnitine deficiency. Patients with organic acidurias exhibit an increased excretion of carnitine esters and an insufficiency of free carnitine. Carnitine supplementation may ameliorate the metabolic disturbance. Secondary carnitine deficiency has also been described in patients receiving chronic valproic acid therapy. Hemodialysed chronic renal patients may benefit from L-carnitine therapy and show improvement of their hyperlipidemia. Nutritional carnitine deficiency can be primarily expected in premature infants receiving a carnitine free diet, since these infants have an impaired capacity for carnitine biosynthesis.
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PMID:[Carnitine deficiency]. 301 17

The multisystem involvement in acute pancreatitis (AP) is a reflection of the pancreatic gland's capacity to produce a number of potent vasoactive peptides, hormones, and enzymes. The various prognostic criteria are early evaluations of these metabolic derangements. The pathogenesis of hypocalcemia, long recognized as an indicator of severity of AP, is multifactorial. Imbalances of parathyroid hormone (PTH)-calcitonin, the interactions of glucagon, gastrin and other pancreatic hormones with PTH-calcitonin, the role of free fatty acids in binding serum calcium with albumin, and the translocation of calcium ion in muscles and liver, have been recently described but remain conflicting theories. Yet, the time-honored theory of calcium-soap formation enjoys wide acceptance. Hyperglycemia, hypoglycemia, and occasional ketoacidosis in acute pancreatitis have been studied thoroughly. The complex cause-and-effect relationship between hyperlipidemia with acute pancreatitis needs further study. The coagulation abnormalities seem to be initiated by activated trypsin, and their role in microvascular coagulation appears to form a unifying hypothesis for major organ dysfunction, but this requires further investigation. Adult respiratory distress syndrome may be the result of active enzymes that digest pulmonary surfactant and/or microvascular thrombosis. The depression of cardiac function and shock are suspected to be secondary to vasoactive peptides such as bradykinin, or myocardial depressant factor, whose structure has yet to be elucidated. The renin-angiotensin alterations and renal complications in acute pancreatitis have received scant attention in the literature. The onset of moderate visual disturbances, or even blindness, in a patient with acute pancreatitis as a result of retinal vessel thrombosis is fortunately uncommon. Rare but interesting are the manifestations such as subcutaneous fat necrosis, arthralgia, and pancreatic encephalopathy. Despite the extensive literature on the complexities of the pathogenesis of complications of acute pancreatitis, there have been very few advances in the prevention and management of specific complications. It is hoped that further work on modification of enzymatic disturbances induced in acute pancreatitis will result in its effective treatment and prevention of serious complications.
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PMID:Systemic complications of acute pancreatitis. 328

Patients with deficient activity of hepatic glucose-6-phosphatase (glycogen storage disease type I [GSD-I]) have fasting-induced hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and a markedly increased capacity for ethanol elimination. The mechanism(s) responsible for the rapid ethanol elimination is not known but has been thought to be directly related to the enzyme defect. We postulated however, that the increased elimination of ethanol was an adaptive phenomenon that would revert toward normal with correction of other blood abnormalities by long-term maintenance of normal blood glucose concentration. Six patients were observed before treatment (group A), and four of the six were observed again 3 to 6 months after dietary treatment had normalized all blood abnormalities (group B). Patients received 16 ml/m2 absolute ethanol as a 5% solution in 0.9% sodium chloride over a 20-minute period. The rate of ethanol elimination was significantly greater (P less than 0.03) in group A than in group B (55.1 +/- 11.1 vs. 37.5 +/- 8.6 mg/dl/hr). Changes in lactate level after ethanol were also significant between the two groups (P less than 0.005). Group A showed a decrease from 9.4 +/- 0.5 to 6.4 +/- 0.4 mEq/L, whereas group B showed an increase in lactate level from 2.7 +/- 0.2 to 4.4 +/- 0.64 mEq/L. Ethanol induced no significant change in blood glucose concentration in group A, whereas there was a significant increase (P less than 0.03) in group B from 93 +/- 6 to 123 +/- 9 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid ethanol elimination in patients with type I glycogen storage disease is an adaptive change resulting from recurrent hypoglycemia. 345 5

A 3-year-old child with glycogenosis due to hepatic phosphorylase kinase deficiency is described. His clinical presentation was unusually severe. Biochemical studies revealed a lack of hypoglycemia, the presence of marked ketosis and hyperlipidemia, and a normal glycemic response to glucagon and to loading with galactose, fructose, and alanine. The ketosis was reversed by glucagon administration. Changes in plasma concentrations of lactate, pyruvate, beta-OH butyrate, and alanine in response to glucagon, galactose, fructose, and alanine administration are reported. The child responded poorly to a high protein diet. His condition improved markedly with a high carbohydrate diet. The significance of the findings is discussed.
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PMID:Clinical and laboratory observations in a child with hepatic phosphorylase kinase deficiency. 345 48

The toxicities of free doxorubicin (F-DOX) and liposome-associated doxorubicin (L-DOX) were investigated in inbred BALB/c and outbred Sabra mice treated iv with 5, 7.5, and 10 mg doxorubicin (DOX)/kg body weight every 2 weeks up to 8 injections and observed for 6 months. Sonicated liposomes containing phosphatidylcholine, phosphatidylglycerol, and cholesterol were used. The lethal effect was reduced in mice treated with L-DOX as compared to mice treated with F-DOX. At a dose of 7.5 mg DOX/kg, 100% of mice receiving the L-DOX survived a cumulative dose of 60 mg/kg administered over 98 days, while 92% of mice receiving the F-DOX died. Two distinct patterns of death were observed: an acute phase type occurring early after injection of high doses of DOX and apparently related to gastrointestinal toxicity and a delayed phase type requiring a long latency after initial drug exposure and characterized by a complex pattern of abnormalities. Delivery of DOX by liposomes effectively protected against both types of lethal effects. Reduced toxicity of L-DOX resulted in reduced body and organ weight losses, reduced severity of pathologic changes, and fewer blood biochemical alterations. The pathological damage to the heart muscle found in mice treated with L-DOX was less severe than with F-DOX, and in some cases it was reversible. Nephrotoxicity was extremely frequent and severe among F-DOX-treated mice, while it was totally insignificant among L-DOX-treated mice. Hyperlipidemia, hypoglycemia, and glycogen-depleted hepatocytes were characteristic findings in mice treated with F-DOX. Altogether, the data obtained in this study indicate that liposomes significantly diminish the toxicity of DOX with the use of an intermittent schedule of chemotherapy. In addition to changes in tissue distribution as a mechanism of reduced toxicity, it is proposed that DOX associated with liposomal lipids interacts less efficiently than the free drug with target intracellular phospholipids.
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PMID:Comparative long-term study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. 346 Dec 7

The effect of body weight excess and hyperlipidemia on stimulated growth hormone (GH) secretion and serum somatomedin activity (SSA) has been investigated. Among 40 obese men gradually impairment of GH secretory response during the insulin hypoglycemia test was shown. Propranolol-L-DOPA administration elicited satisfactory GH secretory response only in the subgroup of patients with the mild weight excess. SSA was found to be in the normal range among the whole group of obese patients, however, it was significantly depressed in subjects with average weight excess higher than 100%. Obese men with hypertriglyceridemia and hypercholesterolemia presented low SSA even when their weight excess was relatively moderate, i.e., 52% and 57%, respectively.
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PMID:Serum somatomedin activity and growth hormone level in obese men: dependence on degree of obesity and hyperlipidemia. 355 17

1. GSD-I is described in a child with partial deficiency of hepatic glucose-6-phosphatase. 2. Growth retardation and hepatosplenomegaly were major clinical features. 3. Hyperlipidaemia, lactic acidaemia, hyperuricaemia and reduced uric acid clearance were major biochemical findings. 4. Although the glucose response to glucagon and galactose was impaired, there was a striking absence of hypoglycaemia which may be attributable to residual catalytic activity of the enzyme. 5. Preliminary studies of the crude liver enzyme showed it to have a normal pH inactivation profile and apparent Km with a reduced Vmax. 6. No evidence of increased PP-ribose-P availability in fresh liver tissue was detected. 7. Continuous glucose feeding resulted in accelerated growth without complete correction of lactic acidosis or hyperuricaemia. 8. GSD-I with partial deficiency of hepatic glucose-6-phosphatase should be considered in patients with gout or hyperuricaemia associated with hypertriglyceridaemia and lactic acidaemia even in the absence of hypoglycaemia.
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PMID:Clinical and enzymological studies in a child with type I glycogen storage disease associated with partial deficiency of hepatic glucose-6-phosphatase. 615 47


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