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)

It has been established previously that nephrotic hyperlipidemia is characterized by both an increase in lipid synthesis and a defect in removal of lipoproteins. The relationship between these defects and altered albumin metabolism is uncertain. One hypothesis is that hepatic lipogenesis increases in parallel with albumin synthesis. To test this hypothesis, albumin synthesis was increased in nephrotic rats fed an 8.5% protein diet (LPN) by increasing dietary protein to 40% (HPN). Proteinuria was modulated in half of the rats fed 40% protein by enalapril (HPE). Albumin synthesis was the same in both HPN and HPE, but proteinuria was reduced in HPE compared to HPN, and so were serum cholesterol and triglycerides (TG). To examine the effect of serum albumin on lipid clearance in the absence of proteinuria, plasma clearance of chylomicrons (CM) and VLDL was measured in Nagase analbuminemic rats (NAR) and found to be no different than in normal SD rats. When proteinuria was induced in NAR and in SD rats, a severe and identical defect in both CM and VLDL clearance was acquired in both groups and blood lipid levels were increased to a similar degree in both groups. Neither hyperlipidemia nor defective removal of lipoproteins from the circulation are linked to albumin synthesis or serum albumin concentration but result, at least in part, from proteinuria. Postheparin lipoprotein lipase (LPL) activity was reduced slightly in nephrotic animals compared to nonnephrotic controls, but the most striking finding was a highly significant decrease in postheraprin LPL activity in normal NAR compared to SD rats (P less than 0.001), suggesting that reduced LPL activity is not responsible for reduced clearance of CM and VLDL in nephrotic rats.
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PMID:Proteinuria, not altered albumin metabolism, affects hyperlipidemia in the nephrotic rat. 238 6

To elucidate the mechanism for thrombus formation in hypoalbuminemic and hyperlipidemic subjects, the experimental thrombus formation was analyzed in Nagase analbuminemic rats (NAR). The mutant rat reveals similar biochemical findings to those of NS, such as hyperlipidemia. When thrombus was induced in a small branch of the mesenteric artery by inserting a glass micropipette, thrombus formation was observed within 4 min in NAR and Sprague-Dawley rat (SDR). In SDR, the thrombus gradually grew up in size and detached from the inserted glass micropipette within 4 min after its formation. In contrast, the thrombus formed in NAR did not dissociate from the micropipette until 10-13 min after its formation. The maximum size of the thrombus formed in NAR was about 4 times larger than that in SDR. In the presence of fibrin, the plasma samples from NAR inhibited the activity of tissue-plasminogen activator (t-PA) 1.7 times more potently than did SDR plasma. Plasma gamma 2-plasmin inhibitor activity was significantly higher than that in SDR. Albumin significantly enhanced the t-PA-catalyzed activation of plasminogen, suggesting that the serum albumin might contribute, at least in part, to the plasma fibrinolytic activity. Thus, the higher thrombogenic potential in NAR than in SDR might be due to the reduced thrombolytic activity in NAR.
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PMID:Dynamic aspects of thrombus formation in mutant analbuminemic rats. 238 31

Hyperlipemia is a common manifestation of the nephrotic syndrome. Serum lipid concentrations have been observed by others to be negatively correlated with serum protein concentration. Hyperlipemia has been postulated to result from a coordinate increase in the synthesis of both albumin and lipoproteins, as well as from their decreased catabolism. Simultaneous measurements of serum lipid concentration and the rate of albumin synthesis have not been previously reported. We measured the rate of albumin synthesis, urinary albumin loss, serum albumin, protein, cholesterol and triglyceride concentration in 13 nephrotic patients. Changes in the rate of albumin synthesis and in urinary albumin excretion were induced in eight patients by alteration in dietary protein intake. The resultant changes in serum triglyceride and cholesterol were analyzed by multiple regression analysis. The rate of albumin synthesis measured while patients were eating a low protein diet was 12.61 +/- 1.20 g/1.73 m2/day, well within normal limits, yet both serum triglyceride and cholesterol concentrations were markedly elevated (265 +/- 65 mg/dl and 325 +/- 44 mg/dl, respectively). Albumin synthetic rate increased to 17.60 +/- 1.25 g/1.73 m2/day when dietary protein intake was increased, while serum triglyceride and cholesterol concentrations changed little; triglyceride concentration was 306 +/- 75 mg/dl and cholesterol 376 +/- 55 mg/dl. Serum cholesterol concentration, by multiple regression analysis, was dependent only upon the renal clearance of albumin P less than 0.0001, and changes in serum cholesterol concentration was dependent only upon changes in the renal clearance of albumin, P less than 0.001. Serum cholesterol concentration was completely independent of the rate of albumin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Albumin synthesis, albuminuria and hyperlipemia in nephrotic patients. 361 8

Anthropometric measurements, sixteen specific plasma proteins, triglycerides, cholesterol, urea and creatinine were measured at 4-monthly intervals for 1 year in 15 patients on CAPD. Delayed hypersensitivity skin tests were performed on 11 patients at the start and after 4 and 12 months. Body weight increased due mainly to a mean increase in 'calculated' body fat of 2.0 kg with increases in cholesterol, triglycerides and apolipoprotein B. Gain in fat correlated with the daily supply of dextrose in the dialysis fluid. Albumin, transferrin, prealbumin and retinol-binding protein decreased in 8 patients who intermittently ate less than 1.3 g protein/kg/day. A high concentration of dextrose in the dialysis fluid probably caused loss of appetite. Peritonitis resulted in increases in acute phase proteins although other plasma proteins decreased. Skin test responses indicated improvement in cell-mediated immunity during continuous ambulatory peritoneal dialysis (CAPD). The incidence of peritonitis and length of stay in hospital were greater in the patients who were hypoalbuminaemic probably due to impairment of the humoral mechanism. Dextrose in dialysis fluid may contribute to hyperlipidaemia and malnutrition with impairment of immunocompetence.
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PMID:Nutrition and delayed hypersensitivity during continuous ambulatory peritoneal dialysis in relation to peritonitis. 372 25

A colorimetric method was developed for the determination of nonenzymatically glycated albumin and adapted to a Flexigem centrifugal analyzer. Albumin was separated from serum or plasma using Sepharose-blue dextran affinity chromatography. The stable ketoamine linkage in glycated albumin reduced a tetrazolium salt to its colored formazan. Glycated human serum albumin was used as the standard and optimum conditions for the assay were established. Recovery of glycated albumin was quantitative. The coefficients of variation for within-run and day-to-day precision were 4.6% and 8.5%, respectively. The labile aldimine fraction, lipemia, icterus, hemolysis and type of anticoagulant used did not affect the results. The non-diabetic reference interval for this method was 7.9-11.6% glycated albumin, and normal and diabetic populations can be clearly discriminated (p less than 0.005). Values obtained with this method correlated well with a thiobarbituric acid assay (r = 0.974) but less so with those for glycated hemoglobin (r = 0.35).
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PMID:Colorimetric determination of non-enzymatically glycated albumin. 395 2

A case report of cholestatic jaundice in a 25 year old woman, who had had jaundice at age 4 years, and had taken Stediril (a combined oral contraceptive) for 1 month, implicates either the pill or a possibly hereditary hyperlipidemia. The jaundice developed in 2 weeks with vomiting, epigastric pain, anorexia, then discolored urine and feces, and intense pruritus. On hospitalization the patient had moderate bilirubinemia (56 mg/1), low alkaline phosphatase (13 U.K.) and slightly high serum glutamate pyruvate transaminase (270 U.W.). There were elevated serum cholesterol (3 gm/1), triglycerides (2.05 gm/1), total lipids (10.6 gm/1), and a definitely increased pre-beta lipoprotein, suggesting hyperlipidemia type IV (Frederickson classification). Liver biopsy showed fibrosis of the portal spaces lymphocytic infiltration, canalicular and intrahepatocytic thrombi. On laparoscopy the liver had a regular lower border, normal volume color and surface. Albumin, prothrombin and flocculation tests were normal. The patient's jaundice lasted about 1 month, then liver function slowly improved, although pruritus remained intense. Probably this jaundice was due to oral contraceptives, in a patient predisposed either by jaundice in childhood or endogenous hyperlipidemia.
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PMID:[Cholestatic icterus due to oral contraceptives]. 426 76

The chemical measurements on our Technicon SMAC of lipemic sera before and after clearing lipemia by ultracentrifugation showed that uric acid, creatinine, carbon dioxide, calcium, phosphorus, potassium, and alkaline phosphatase were not affected significantly by lipemia, whereas sodium, urea, glucose, chloride and total protein showed small but significant increases with averages of less than 1.9 percent. Albumin showed a significant decrease of 1.2 percent. In contrast, the results for the enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) showed striking differences between pre- and post-centrifuged sera in a number of specimens. With lactate dehydrogenase, thirty-two of fifty specimens registered an increase in activity while with the aminotransferases, thirty-five and forty-one out of fifty specimens showed a decrease in aspartate aminotransferase and alanine aminotransferase activities, respectively. Although much of the lipemic interference can be explained by the volume displacement of serum by lipids or by interference by lipemia with colorimetry, the anomalous effects observed with the enzymes indicate the possibility of other, as yet, undetermined factor(s).
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PMID:The effect of hyperlipidemia on Technicon SMAC measurements. 712 23

OBJECTIVE--To determine the prevalence of incipient and overt nephropathy in African-American subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic. Contributory factors, such as blood pressure (BP), duration and age at onset of diabetes, hyperglycemia, hyperlipidemia, and body mass index (BMI) also were evaluated. RESEARCH DESIGN AND METHODS--We recruited 116 African-American subjects with NIDDM for this cross-sectional, descriptive, and analytical study. BP, BMI, 24-h urine albumin excretion, creatinine clearance, serum creatinine, lipids, and GHb levels were measured. Albumin excretion rate (AER) was calculated, and subjects were divided into three groups: no nephropathy (AER < 20 micrograms/min), incipient nephropathy (AER 20-200 micrograms/min), and overt nephropathy (AER > 200 micrograms/min). Frequency of hypertension and nephropathy was analyzed by chi 2 testing, group means were compared using analysis of variance, and linear correlations were performed between AER and other variables. Multiple regression analysis was used to examine the association of these variables while controlling for the effects of other variables. RESULTS--Increased AER was present in 50% of our subjects; 31% had incipient and 19% had overt nephropathy. Hypertension was present in 72.4%; nephropathy, particularly overt nephropathy, was significantly more prevalent in the hypertensive group. Mean BP and diastolic blood pressure (dBP) were higher in the groups with incipient and overt nephropathy, and systolic blood pressure (sBP) was increased in overt nephropathy. Men with either form of nephropathy had higher sBP, dBP, and mean BP, whereas only women with overt nephropathy had increased sBP and mean BP. Subjects with incipient or overt nephropathy had a longer duration of diabetes, and those with overt nephropathy had a younger age at onset of diabetes. By multiple regression analysis, AER correlated with younger age at diabetes onset, but not with diabetes duration. No correlation with age, lipid levels, or GHb was noted. BMI correlated with AER. CONCLUSIONS--Incipient and overt nephropathy were observed frequently in these African-American subjects with NIDDM. Albuminuria correlated with BP, younger age at diabetes onset, and BMI. Association of albuminuria and increased cardiovascular mortality may place 50% of inner-city African-American patients with NIDDM at risk for developing cardiovascular complications.
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PMID:Incipient and overt diabetic nephropathy in African Americans with NIDDM. 802 85

The nephrotic syndrome is a consequence of urinary loss of intermediate-sized plasma proteins and the resulting homeostatic responses to those losses. Plasma protein composition is changed greatly. Pathophysiologic changes are a consequence of the nature of the proteins lost and of the proteins that are increased in plasma to replace them. Plasma oncotic pressure (pi) falls because of the replacement of relatively small plasma proteins by larger ones. Decreased pi increases transudation of fluid into the interstitium and favors edema. This is exacerbated by causing renal insensitivity to atrial natriuretic factor (ANF), primary renal sodium retention, and plasma volume expansion. Many proteins lost in the urine, such as erythropoietin and IgG, are not defended by increased synthesis. Their loss may result in reduced immunity, anemia, and endocrinopathies. Albumin synthesis can be increased by dietary protein augmentation; however, urinary protein losses also increase, offsetting any palliative effect of increased albumin synthesis on albumin stores. The synthesis of many other proteins secreted by the liver is also increased, causing an elevation in plasma levels of several large proteins, including lipoproteins and elements of the coagulation cascade. This results in hyperlipidemia and, in conjunction with the urinary loss of smaller proteins that impede coagulation, a hypercoagulable state. Lipoprotein catabolism is also reduced as a consequence of proteinuria contributing to increased lipid levels.
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PMID:Nonrenal complications of the nephrotic syndrome. 819 77

Albumin deficiency is accompanied by a reduction in red cell deformability and blood hyperviscosity. Albumin deficiency increases plasma fibrinogen and triglyceride levels and may alter red cell membrane lipid composition. These options, which could all contribute to reduced red cell deformability (RCD) and hyperviscosity, were studied in the Nagase analbuminemic rat (NAR), a mutant Sprague Dawley rat (CON), characterized by normal total protein levels, with an absolute deficiency of albumin, but elevated levels of non-albumin proteins and hyperlipidemia. Plasma protein-binding of the polar phopholipid lysophosphatidylcholine (LPC) was markedly decreased. LPC comprised only 26 +/- 1% of total plasma phospholipids as compared to 42 +/- 2% in CON. NAR red cells in CON plasma had a viscosity that was similar to CON red cells in CON plasma. Conversely, CON red cells in NAR plasma show an increased viscosity as compared to CON red cells in CON plasma. The maximum deformation index of both NAR and CON red cells was markedly decreased in NAR plasma as compared to either NAR or CON cells in CON plasma (0.04 +/- 0.03 and 0.02 +/- 0.02 vs. 0.22 +/- 0.06 and 0.15 +/- 0.04, respectively; P < 0.05). Thus, plasma composition causes hyperviscosity and reduced RCD in NAR. Fibrinogen is not responsible since red cells in serum and red cells in plasma had a similar viscosity and differences in viscosity and RCD between NAR and CON were maintained. Plasma triglycerides are also not responsible since the viscosity of red cells in serum with a 50% reduction in triglycerides was not reduced. LPC levels in red cells were increased in NAR (8.7 +/- 0.2 vs. 5.5 +/- 0.3% of total phospholipids; P < 0.01). Adding albumin to NAR blood dose-dependently decreased whole blood viscosity, despite marked increases in plasma viscosity, and increased RCD of NAR cells (from 0.04 +/- 0.03 to 0.21 +/- 0.01; P < 0.05). There was also some effect on CON RCD of similar albumin addition to CON blood (from 0.15 +/- 0.04 to 0.29 +/- 0.03; P < 0.05). Adding albumin to NAR blood reduced red cell LPC content and increased plasma LPC content in a dose-dependent fashion, whereas there were only slight effects of adding albumin to CON blood. There was a reciprocal relation between red cell LPC and the other polar phospholipids in the red cell membrane, probably indicating exchange. The maximum deformability index of either NAR or CON cells was not affected much by adding LPC to CON plasma (NAR, from 0.22 +/- 0.06 to 0.18 +/- 0.10; CON, from 0.15 +/- 0.04 to 0.12 +/- 0.05; NS), whereas adding LPC to NAR plasma caused the red cells to become rigid. Adding LPC to CON red cells in NAR plasma caused a much stronger increase in relative LPC content (from 6.6 +/- 0.7 to 10.9 +/- 0.9%; P < 0.05) than adding LPC to CON red cells in CON plasma (from 5.6 +/- 0.4 to 6.4 +/- 0.8%; NS). Thus, in the absence of albumin, LPC in red blood cells is increased. As a consequence of the latter, RCD is decreased and whole blood viscosity increased. Alterations in red cell phospholipids are far more important than increases in plasma fibrinogen or triglycerides in determining hyperviscosity of blood and reduced RCD in NAR.
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PMID:Hypoalbuminemia causes high blood viscosity by increasing red cell lysophosphatidylcholine. 929 Nov 98


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