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)

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

Heymann nephritis was induced in rats with spontaneous hypertension (group HN), and renal lesions were investigated at the twentieth and thirty-sixth week. An identical group given antihypertensive drugs (group HN-AH), an identical group given anticoagulant drugs (group HN-AC), and a nonimmunized control group of spontaneously hypertensive rats (controls) were also examined. Massive proteinuria, hypoalbuminemia, and hyperlipidemia were present in groups with induced Heymann nephritis (HN, HN-AH, and HN-AC). Coagulation studies demonstrated a shortening of prothrombin time, an increase in serum fibrinogen and thrombocytes, and a reduction of antithrombin III in the groups HN and HN-AH. Necrotizing lesions were observed only in group HN and without further elevation in blood pressure. Intravascular thrombosis was prominent at the twentieth week, and marked fibrinoid necrosis appeared at the thirty-sixth week. These vascular lesions were not observed in the HN-AH, HN-AC, and control groups. Thus, a state of hypercoagulability in addition to high blood pressure probably contributes to the genesis of necrotizing vascular lesions in spontaneously hypertensive rats with nephritis.
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PMID:Necrotizing vascular lesions in spontaneously hypertensive rats with nephrotic syndrome: hypercoagulability as a contributory factor. 638 12

Prothrombin fragment 1.2 (F1.2) is an activation peptide generated during a critical event of blood coagulation, the conversion of prothrombin to thrombin. As a marker of thrombin generation, F1.2 has clinical potential in assessing thrombotic risk and monitoring anticoagulant therapy. In developing a highly specific, monoclonal antibody-based immunoassay of human plasma F1.2, we generated six murine anti-F1.2 monoclonal antibodies, using as immunogen a synthetic peptide (sequence: CGSD-RAIEGR) similar to the unique carboxyl terminus of F1.2. Each antibody bound F1.2 but not prothrombin. Epitope mapping studies with one antibody (5-3B) showed that optimum binding required six to eight amino acids plus a terminal arginine to emulate the F1.2 carboxyl terminus. A quantitative sandwich ELISA for human plasma F1.2 was configured with monoclonal antibody 5-3B as the capture antibody and peroxidase-labeled polyclonal antibodies to the F1.2 amino-terminal region as detector antibodies. Calibrators were prepared by adding purified F1.2, 0-10 nmol/L, to F1.2-depleted plasma. Assay characteristics included the following: mean (+/- SD) analytical recovery of 98% +/- 13%; no interference from lipemia, hemolysis, icterus, or thrombolytic agents; 0.08 nmol/L sensitivity; and mean intra- and interassay imprecision (three lots) < 12% at both low and high concentrations of F1.2.
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PMID:Monoclonal antibodies specific for prothrombin fragment 1.2 and their use in a quantitative enzyme-linked immunosorbent assay. 847 48

The effect of hyperlipidaemia on endothelial cell haemostatic properties was examined using ex vivo studies on aortic segments obtained from fat-fed Chinchilla rabbits, mounted in a template device which exposed the luminal surface. Exposure of arterial endothelium to lipids resulted in marked enhancement of externally exposed anionic phospholipids, detected using either fluorescence microscopy with the probe merocyanine 540 or by binding of 125I-polymyxin B and 125I-Annexin V. Consistent with the known procoagulant properties of anionic phospholipid, following the lipid and cholesterol-rich diet intake, intact endothelial cells demonstrated enhanced binding of radioiodinated factors IX/IXa and Xa, and enhanced factor IXa/VIII-dependent factor X activation and factor Xa-factor Va-mediated prothrombin activation. Both factor Xa and thrombin formation were blocked, in large part, by polymyxin B, suggesting dependence of the reaction on anionic phospholipids. Consistent with these results, evidence of increased activation of the coagulation mechanism in vivo was observed in hyperlipidaemic animals, as assessed by a three-fold increase in levels of circulating antithrombin-protease complexes, compared with normolipidaemic controls.
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PMID:Intrinsic procoagulant surface induced by hypercholesterolaemia on rabbit aortic endothelium. 829 24

Mortality rates associated with cardiovascular disease (CVD) are high in long-term dialysis patients. Increased levels of plasma fibrinogen (FBG), coagulation factor VII (FVII), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) as well as hyperlipidemia are regarded as important risk factors for CVD. To investigate whether there are differences in the risk of CVD between chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients, serum lipid levels and plasma FBG, FVII, t-PA, and PAI-1 levels were measured in 17 patients on HD and 17 patients on CAPD. FBG was measured by the thrombin time method, FVII activity (FVIIc) by the chromogenic prothrombin time method, and t-PA and PAI-1 activity by the chromogenic substrate assay. No difference was found in body mass index (BMI) between HD and CAPD patients. Total cholesterol (TC), TC/high-density lipoprotein (HDL)-C ratio, low-density lipoprotein (LDL)-C, and triglycerides (TG) were significantly increased, and HDL-C was significantly decreased in CAPD patients compared with HD patients. FBG and FVIIc were significantly elevated in CAPD patients compared with controls or HD patients. T-PA activities were significantly higher in HD and CAPD patients than in controls. CAPD patients showed significantly higher PAI-1 activities than controls or HD patients. Significant positive correlations were found between FBG or FVIIc and TC, between FBG and LDL-C or TG, and between FVIIc and LDL-C in these patients. T-PA showed significant negative correlations with FBG, PAI-1, TC, LDL-C, and TG. There was a significant positive correlation between PAI-1 and TG and a significant negative correlation between PAI-1 and HDL-C. We conclude that CAPD patients may have a greater risk of CVD than do HD patients, and that coagulation and fibrinolytic activity are correlated with lipid disorders in these patients.
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PMID:Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. 865 Dec 50

Out of 12 patients with primary hyperlipidemia (HL) included in the study ischemic heart disease was diagnosed in 4 and hypertension stage I-II in 6 patients. HL stage II B, III, IV and V was registered in 7, 2, 2 and 1 patients, respectively. Hypolipidemic therapy included hypolipidemic diet and Lipanor (Sanofi-Chinoin-Winthrop, France) in a dose 100 mg once a day after evening meal. The course lasted 3 months. Blood serum was examined for concentrations of total cholesterol (CS), triglycerides (TG), CS of HDLP, glucose, uric acid, prothrombin, fibrinogen, alanine and asparagine transaminase, alkaline phosphatase, creatinine, total bilirubin. After 1 month of lipanol treatment mean total CS concentration in the serum fell by 21.9% and remained such for 2-3 months of treatment. 1 month after the drug discontinuation mean concentration of total CS was under the initial one by 4.65%. Mean serum concentrations of TG 1 month after treatment decreased by 41.7%, after 2 months by 48.8%. Mean concentration of HDLP CS after 1 month of treatment rose by 19.2% and by 33.1% after one more month. 1 month after Lipanor discontinuation mean HDLP CS concentration exceeded the baseline level by 16%. Fibrinogen and prothrombin index declined. Hypolipidemic effect of Lipanor varied from case to case.
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PMID:[A trial of the use of the hypolipidemic preparation Lipanor (ciprofibrate) in patients with primary hyperlipidemia]. 877 89

In vitro studies in purified plasma systems have suggested that triglyceride-rich lipoproteins such as chylomicrons, very low density lipoproteins, and their remnants promote activation of factor VII through activated factor XII (XIIa) and the intrinsic coagulation pathway. We specifically examined the roles of factors XII, XI, and IX in activation of factor VII during alimentary lipemia in vivo in humans and addressed the issue of whether generation of activated factor VII (VIIa) is accompanied by increased thrombin production. For this purpose XIIa, factor IX activation peptide (IXP), VIIa, prothrombin fragment 1 + 2 (F1 + 2), and thrombin-antithrombin complex (TAT) were determined in plasma samples taken before and 3, 6, and 9 hours after intake of a mixed meal type of oral fat load in 24 healthy men The VIIa response to fat intake was also determined in 7 patients with single coagulation-factor deficiency, of whom 2 were deficient in factor XII, 2 in factor XI, and 3 in factor IX. Postprandial activation of factors IX and VII occurred in the healthy individuals, whereas the plasma levels of XIIa did not change in response to the test meal. Of note, plasma concentrations of F1 + 2 were unaltered during alimentary lipemia, and TAT levels showed a small decrease (P < .05) in the 3-hour sample compared with the fasting level, indicating that thrombin generation is not stimulated in the postprandial state, despite the generation of activated factor IX (IXa) and VIIa. Factor VIIa increased in the postprandial period in the 2 factor XII-deficient patients who underwent the oral fat tolerance test but appeared to remain unchanged in the factor XI- and factor IX-deficient patients. Therefore, the current concept that activation of factor XII plays a pivotal role in initiating the sequence of events linking postprandial lipemia to activation of factor VII is contradicted by the present study. Whether activation of factor XI by triglyceride rich lipoproteins initiates these reactions needs to be demonstrated in future studies.
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PMID:In vivo demonstration in humans that large postprandial triglyceride-rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway. 891 Dec 71

We investigated the usefulness of the fluorogenic prothrombin time (FPT) for detection of hypercoagulability and its association with hyperlipidemia in 19 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy control subjects, compared with plasma levels of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and D-dimer. We also evaluated the effect of bezafibrate on hypercoagulability in 10 hyperlipidemic NIDDM patients. The plasma levels of FPT and fibrinogen were significantly higher in hyperlipidemic NIDDM patients than in normolipidemic NIDDM patients and controls. Plasma levels of PAI-1 and D-dimer were significantly higher in normolipidemic and hyperlipidemic NIDDM patients compared with controls. The FPT was correlated with the HbA1c, the body mass index, and levels of total cholesterol, fibrinogen and PAI-1. Six-months therapy with bezafibrate reduced the levels of FPT, triglycerides and basal insulin, but did not alter levels of fibrinogen, PAI-1 and D-dimer. Our results showed that the FPT was useful for detection of hypercoagulability and evaluation of the effect of drugs. The increased FPT in patients with NIDDM suggested that hypercoagulability was present in association with hyperlipidemia.
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PMID:Effect of bezafibrate on hypercoagulability assessed by fluorogenic prothrombin time in hyperlipidemic patients with non-insulin-dependent diabetes mellitus. 921 24

Metabolism in man is regulated by complex hormonal signals and substrate interactions, and for many years the clinical focus has centred on the metabolic and hormonal picture after an overnight fast. More recently, the postprandial state, i.e. 'the period that comprises and follows a meal', has received more attention. The oral glucose tolerance test (OGTT), although highly non-physiological, has been used largely as a model of the postprandial state. Epidemiological studies have shown that, when 'impaired', oral glucose tolerance is associated with an increased risk of cardiovascular disease. Postprandial hyperlipidaemia has been investigated more recently in epidemiological, mechanistical and intervention studies, most of which indicate that high postprandial triglyceride levels, and particularly postprandial rich triglyceride remnants, constitute an increased risk for cardiovascular disease. Recent studies have shown that excessive postprandial glucose excursions are accompanied by oxidative stress and, less well known, activation of blood coagulation (increase in circulating D-dimers and prothrombin fragments). The mechanisms through which increased postprandial glucose levels and lipid concentrations may damage endothelial cells on blood vessel walls appear to be complex. These mechanisms include the activation of protein kinase C, increased expression of adhesion molecules, increased adhesion and uptake of leucocytes, increased production of proliferative substances such as endothelin, increased proliferation of endothelial cells, increased synthesis of collagen IV and fibronectin, and decreased production of nitric oxide (NO). In conclusion, the 'postprandial state' cumulatively covers almost half of the nycthemeral period, and its physiology involves numerous finely regulated motor, secretory, hormonal and metabolic events. Epidemiological and mechanistical studies have suggested that perturbations of the postprandial state are involved in cardiovascular disease. Correcting the abnormalities of the postprandial state must form part of the strategy for the prevention and management of cardiovascular diseases, particularly those that are associated with diabetes mellitus.
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PMID:The postprandial state and risk of cardiovascular disease. 986 96

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.
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PMID:Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats. 1089 50


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