Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

In a study of structure-activity relationship with drug-induced nephropathy two lipoxygenase inhibitors, the N-hydroxyurea derivative 70C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxyurea) and the N-hydroxamic acid analogue 360C ((E)-N-{3-[3-(4-fluorophenoxy) phenyl]-1-(R, S)-methylprop-2-enyl}-N-hydroxamic acid), were administered to rats. 70C and 360C were dosed to female Wistar rats at 100 mg/kg po daily for 7 days. Another group of rats was given a single intravenous bolus dose of puromycin aminonucleoside (PAN) at 100 mg/kg. Urine samples were collected from all groups during the study and plasma samples were collected after 7 days. Kidneys were excised and fixed for examination by electron microscopy. 70C- and PAN-treated groups both showed early changes in the glomeruli, in which the visceral cells appeared enlarged and showed varying degrees of foot process loss. This foot process loss was associated with decreases in total plasma protein and albumin and increases in the plasma cholesterol, triglycerides, creatinine, and urea were recorded. Marked proteinuria was observed in both the 70C and PAN groups. The foot process loss together with increased proteinuria, hypoalbuminemia, hypercholesterolemia, and lipemia are all characteristic of the human condition, Minimal Change Nephrotic Syndrome. All the biochemical and morphological investigations showed that 360C-treated rats were similar to the control group, suggesting that the hydroxyurea moiety of 70C is responsible, either directly or indirectly, for the induction of the nephrotic syndrome seen in rats.
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PMID:Structure-activity relationship for two lipoxygenase inhibitors and their potential for inducing nephrotic syndrome. 934 98

Twenty-eight mild hypercholesterolemic male and female adults were orally administered psyllium seed for 3 months. After psyllium treatment, the serum total cholesterol, low-density-lipoprotein-cholesterol and atherogenic index significantly decreased, but levels of high-density-lipoprotein-cholesterol, triglyceride and urea nitrogen did not. To determine the parameters associated with the cholesterol-lowering effect in the subjects' backgrounds, both biochemical and hematological parameters, we statistically examined the correlation between pretreatment parameters and the absolute change of total cholesterol level. The absolute change of total cholesterol level showed a direct correlation with the triglyceride level at pretreatment (r=0.41, P=0.03) and had an inverse correlation with urea nitrogen level (r=-0.46, P=0.01) but not with the total cholesterol level (r=-0.18). The change in urea nitrogen level had an inverse correlation with the urea nitrogen level itself at pretreatment (r=-0.82, P=7 x 10[-8]) and had a direct correlation with the triglyceride level (r=0.43, P=0.02). The change in triglyceride level had an inverse correlation with the urea nitrogen level (r=-0.48, P=0.008). Furthermore, the change in total cholesterol level had direct correlations with changes in the triglyceride level (r=0.56, P=0.002) and the urea nitrogen level (r=0.51, P=0.006), but these changes in triglyceride and urea nitrogen level did not correlate significantly. These findings suggest the close association of urea nitrogen and lipid metabolism in hyperlipidemia and psyllium seed treatment.
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PMID:Cholesterol-lowering effects of psyllium seed associated with urea metabolism. 951 18

The aim of the present study was to evaluate the effects of three fibres (sugar-beet fibre, guar gum and inulin) incorporated in the basal diet of healthy dogs at 7 per cent of dry matter (DM). Parameters examined included stool output, water consumption, nutrient digestibility and fasting and postprandial plasma metabolites. All fibres increased wet faecal output; an increase in faecal DM output being observed with sugar-beet fibre only. Sugar-beet fibre and inulin increased daily water consumption. Sugar-beet fibre and guar gum decreased DM digestibility. The three fibres diminished organic matter and crude protein digestibility while ether extract digestibility was decreased by guar gum and inulin. Guar gum induced lower postprandial insulin, alpha-amino-nitrogen and urea plasma concentrations. Guar gum also lowered fasting cholesterolaemia. Sugar-beet fibre and inulin showed no metabolic effects. These physiological properties suggest that guar gum would be a suitable ingredient for dietary therapy of chronic diseases such as diabetes mellitus or hyperlipidaemia in the dog.
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PMID:The influence of sugar-beet fibre, guar gum and inulin on nutrient digestibility, water consumption and plasma metabolites in healthy Beagle dogs. 962 62

The effect of pravastatin on renal function in hypertensive patients with mild renal dysfunction and hyperlipidemia was examined. A total of 57 subjects given dihydropyridine calcium blockers were randomly assigned to placebo (n = 25) and pravastatin groups (n = 32). The period of study was 6 months. In the placebo group, lipid metabolism did not change throughout the study period, but the serum creatinine concentration (Scr) increased from a baseline of 1.6+/-0.07 mg/dl to 2.1+/-0.2 mg/dl in the 6th month of study and blood urea nitrogen (BUN) increased from 26.2+/-1.1 mg/dl to 32.4+/-30.1 mg/dl. In the pravastatin group, the serum total cholesterol decreased from a baseline of 251.4+/-7.3 mg/dl to 218.2+/-6.5 mg/dl in the 6th month of study, while Scr (1.3+/-0.07 mg/dl vs. 1.3 +/-0.09 mg/dl) and BNU (20.5+/-1.2 mg/dl vs. 21.0+/-1.4 mg/dl) did not change. The change in Scr in the placebo group was significantly different from that in the pravastatin group (F = 3.75, p = 0.05). The slope of the change in 1/Scr was 0.02+/-0.07 dl x mg(-1) x month(-1) in placebo group and -0.01+/-0.03 dl x mg(-1) month(-1) in pravastatin group (P<0.05). The results indicate that pravastatin attenuates the deterioration of renal function in patients with mild renal dysfunction, together with an improvement of lipid metabolism.
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PMID:The effect of pravastatin on renal function and lipid metabolism in patients with renal dysfunction with hypertension and hyperlipidemia. Pravastatin and Renal Function Research Group. 1057 17

Nine patients (aged 18+/-1 years) on maintenance hemodialysis with metabolic acidosis and hyperlipidemia were studied before and after 2 weeks of oral sodium bicarbonate (NaHCO(3)) treatment to correct the acidosis. To control for the effect of additional sodium, they were also studied after 2 weeks of an equivalent amount of oral sodium chloride (NaCl). Oral NaHCO(3 )treatment led to significant increases in venous pH, serum bicarbonate, and serum 1, 25-dihydroxyvitamin D(3) concentrations, but no significant change in total and ionized calcium, phosphate, sodium, potassium, creatinine, blood urea nitrogen, and intact parathyroid hormone concentrations. Oral NaCl did not change any of the biochemical parameters. Before treatment of acidosis, these uremic patients had high serum triglycerides, low serum high-density lipoprotein (HDL) cholesterol, but normal total cholesterol compared with controls. Following 2 weeks of NaHCO(3) treatment, there was a significant decrease in the serum concentrations of triglycerides (P<0.01). HDL and total cholesterol did not change. There were no changes in triglycerides, HDL or total cholesterol from baseline values following 2 weeks of NaCl. Thus treatment of metabolic acidosis ameliorated hypertriglyceridemia but had no effect on HDL and total cholesterol in patients with uremia on hemodialysis. The underlying mechanism may involve 1,25-dihydroxyvitamin D3.
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PMID:Effect of metabolic acidosis on hyperlipidemia in uremia. 1060 43

Renal dysfunction is one of the most common and threatening complications in heart transplant recipients. Even if ciclosporin seems to play a central role in inducing renal damage, other factors may concur or predispose to renal injury. In order to identify factors responsible for renal dysfunction, we retrospectively studied a cohort of 114 cardiac transplant recipients during a follow-up period of at least 3 years. The patients had a normal renal function before and 0.5 months after heart transplantation. Doubling of baseline serum creatinine or attainment of serum creatinine steadily above 176.8 micromol/l (2.0 mg/dl) was used as criterion to define the end-point renal dysfunction. A series of clinical and laboratory variables were obtained from the patients' charts at different time intervals, and their prognostic value for the occurrence of renal dysfunction was calculated by Cox proportional hazards models. 23 out of 114 patients reached the end point after a median time period of 21 months. High serum triglyceride, alanine aminotransferase, alkaline phosphatase, ciclosporin, urea, glucose, and hemoglobin levels were shown to be associated with the development of renal dysfunction. Four variables, i.e., triglyceride, ciclosporin, urea, and alkaline phosphatase, had an independent prognostic value. Our results confirm a role for ciclosporin in inducing renal dysfunction and identify hyperlipidemia and an increased plasma urea level as risk factors for renal dysfunction in heart transplant recipients.
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PMID:Risk factors for chronic renal dysfunction in cardiac allograft recipients. 1064 4

The effect of thymoquinone (TQ), the main constituent of the volatile oil of Nigella sativa seeds, on the nephropathy and oxidative stress induced by doxorubicin (DOX) in rats was investigated. A single intravenous injection of DOX (6 mg/kg) induced a severe nephrotic syndrome (after 5 weeks) associated with hypoalbuminemia, hypoproteinemia, elevated serum urea, hyperlipidemia, and a high urinary excretion of protein, albumin and N-acetyl-beta-D-glucosaminidase (NAG). In the kidney, DOX induced a significant increase in total triglycerides (TG), total cholesterol (TC), and lipid peroxides and a significant decrease in non-protein sulfhydryl (NPSH) content and catalase (CAT) activity. Treatment of rats with TQ (10 mg/kg per day) supplemented with the drinking water for 5 days before DOX, and daily thereafter, significantly lowered serum urea, TG, and TC. Similarly, TG, TC and lipid peroxides in the kidneys of TQ-treated rats were decreased significantly compared with DOX alone. Moreover, NPSH content and CAT activity in the kidneys of TQ-treated DOX group were significantly elevated compared with DOX alone. Treatment with TQ significantly suppressed DOX-induced proteinuria, albuminuria, and urinary excretion of NAG. The results confirm the involvement of free radicals in the pathogenesis of nephropathy induced by DOX. Likewise, the study demonstrates the high antioxidant potential of TQ and its marked effect on the suppression of DOX-induced nephropathy. The data suggest that TQ might be applicable as a protective agent for proteinuria and hyperlipidemia associated with nephrotic syndrome.
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PMID:The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. 1075 8

Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.
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PMID:Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats. 1083 Nov 67

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.
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PMID:Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. 1098 61

Verapamil SR (180 mg) plus trandolapril (2 mg) is a potent antihypertensive combination but the efficacy and safety of this treatment has not been studied fully in hypertensive patients with metabolic disorders. We enrolled 298 patients with mild to moderate hypertension who had at least one of the following disorders: diabetes mellitus, hypercholesterolaemia or mild renal failure. The sitting systolic pressure and diastolic blood pressures were significantly decreased after 12 weeks of treatment. Blood pressure was inadequately controlled in only 24 patients (8.8%). Progressive decreases in blood glucose, total cholesterol, low-density lipoprotein and triglyceride levels were observed during the study. There was no significant change in blood urea nitrogen, creatinine and transaminase levels (p > 0.05). There was a significant decrease in microalbuminuria levels. There was no significant change in glycosylated haemoglobin levels in diabetic patients. Verapamil SR plus trandolapril is an effective drug combination in the treatment of hypertension. It may be used safely in patients with diabetes mellitus, hyperlipidaemia and mild renal failure.
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PMID:Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders. 1121 19


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