Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.
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PMID:A hepatic lipase gene mutation associated with heritable lipolytic deficiency. 167 86

In our opinion, this clinical study demonstrates the intravascular formation of globules, macroglobules and their aggregations both in the association with the type of general anaesthesia and with the operative osteosynthesis of long bones. Within the framework of this study changes in the level of lactic acid in blood serum and of total ketosubstances in blood were followed as well as the levels of total lipids, triglycerides, phospholipides, serum lipase, non-esterified and esterified fatty acids, changes in blood coagulation and 17-ketosteroides in blood. The observed changes supported the opinion that the development of fat globulemia was associated with humoral and physicochemical changes in blood. Repeated evaluations of fat globulemia in plasma are important for studies on pathogenesis and development of fat embolism. In practice, they help: to diagnose especially subclinical forms of fat embolism with non-marked clinical symptoms; to define a suitable term of both primary and delayed operation performed in the period of ending katabolic phase after severe trauma; to define an optimum time for the indication of osteosynthesis to the end of manifest fat embolism; to control positive effects of drugs used for the prophylaction and treatment of fat embolism. In this way it is possible to objective the effectiveness of a rational prophylaxis and treatment of fat embolism. Following factors contribute to macroglobulamia and to manifestation of F. E.: injuries to bones, tissues and organs; stress, posttraumatic shock; severe hemorrhagic hypotension; posttraumatic hypercoagulation with possible binding to the development of a consumption coagulopathy; heavy changes of acid-base balance; increase of catecholamines in plasma; hormonal and general metabolic disturbances; posttraumatic dyslipidemia with special regard to the decrease of beta-lipoproteins and of lipoproteinlipase activity together with the increase of lipoproteins having a very low density and with the occurrence of a significant lipoprotein coalescence. The prospective study on the globulemia changes is based on the following examinations: in 76 injured patients: a short time observation (24 hours) of the globulemia changer after osteosyntheses in general anesthesia. The operative interventions were usually performed 6 to 8 days after injury. in 60 injured patients with fractures (single or multiple fractures, fractures in polytrauma patients): a long-time observation (28 days) of the globulemia changes.
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PMID:Fat globulemia in early diagnostics of traumatic fat embolism. 308 41

We examined the effects of a fibric acid, clinofibrate, on lipoprotein metabolism in 12 hyperlipidemic patients with uremia treated on continuous ambulatory peritoneal dialysis during a 24 week treatment. Daily dose of clinofibrate was 200 mg for the initial four weeks, 400 mg for the second four weeks, and 600 mg for the subsequent 16 weeks. Serum and very-low density lipoprotein (VLDL) triglyceride were decreased by 36% and 48%, respectively. Neither total cholesterol nor apolipoprotein B changed significantly, whereas cholesterol was decreased in VLDL and increased in low (LDL) and high density lipoprotein (HDL) fractions. Post-heparin plasma lipoprotein lipase (LPL) before treatment was not lower than the normal value, and we found no change in LPL activity following clinofibrate. Hepatic triglyceride lipase also did not change. Apolipoprotein (apo) C-II/C-III ratio was low as compared to the normal value before treatment, and the ratio was increased by 38% after the treatment. Decrease in VLDL triglyceride was associated with increase in apo C-II/C-III ratio in all the cases. Abnormal enrichment with triglyceride of LDL and HDL fractions was improved by clinofibrate. Although one patient had a transient and asymptomatic elevation of serum creatine phosphokinase, no patient had muscle pain. There was no accumulation of the drug in the 24 week trial. These results suggest that clinofibrate is an effective and safe approach to the management of dyslipidemia in CAPD patients.
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PMID:Hypertriglyceridemia and lowered apolipoprotein C-II/C-III ratio in uremia: effect of a fibric acid, clinofibrate. 830 36

This paper describes a case of acute pancreatitis occurring in a patient immediately after delivery and in primigravida. The patient had a family case history of dyslipidemia (Type IV). The pregnancy had been complicated by preeclampsia treated at home with nifedipine tablets (one tablet three times a day) with good results on pressure values; lipidic values were high despite dietary measures taken. The baby at birth weighed 3830 g after physiologic labour and a natural delivery. Acute pancreatitis was diagnosed after observation of epigastralgia with irradiation on the left shoulder, vomiting, symptoms of acute abdomen such as sweating, increased pulse rate, hypotension, abdominal pain on palpation, and absence of peristalsis. An analysis of the blood showed high levels of amylase and hyperglycemia, an increase in XDP, and leucocytosis. Instrumental tests such as pancreatic echography revealed an increase in pancreatic volume, uneven structure of the parenchyma and higher levels of liquid in the peritoneum. The patient was moved to intensive-care, a nasal gastric probe inserted, hydroelectrolytic treatment was begun, vital functions monitored, pain kept under control by medical therapy, and antibiotics administered. Subsequent tests showed an improvement in the parameters of pancreatic functions (amylase, lipase, calcium hematic) and their gradual return to normal values. The computerized tomography of abdomen additionally revealed the presence of pancreatic pseudo-cysts and effusion of peritoneal liquid near the right kidney. The patient was discharged after two weeks in the surgical ward. There are many caused of acute abdomen during and immediately after pregnancy, and one of these is acute pancreatitis, though rare (occurring between 1:3800 and 11.467 according to Rabkin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute pancreatitis in pregnancy]. 835 Oct 66

Chronic renal failure (CRF) is associated with hypertriglyceridemia, impaired clearance of very low density lipoproteins (VLDL) and chylomicrons and their remnants as well as triglyceride-enrichment of various lipoproteins. These abnormalities are indicative of depressed lipoprotein lipase (LPL)-mediated hydrolysis of triglycerides in VLD and chylomicrons. In fact, impaired post-heparin lipolytic activity and decreased adipose tissue LPL activity has been previously demonstrated in CRF. The reduction in LPL activity in CRF has been attributed to PTH-induced insulin resistance and the presence of excess lipase inhibitors in uremic plasma. However, the effect of CRF on gene expression of LPL has not been elucidated and was studied here. Heparin-releasable, detergent-extractable and total LPL activities, as well as LPL mRNA of the heart, soleus muscle and fat body were determined in male Sprague-Dawley rats at baseline and on weeks 1, 3 and 6 following 5/6 nephrectomy (CRF group) or sham operation (control group). The CRF group exhibited a marked and steady rise in plasma triglycerides along with a steady decline in LPL activities and mRNA levels of all tissues studied. In contrast, the study parameters remained virtually unchanged throughout the study period in the control group. A strong inverse correlation was found between plasma triglycerides and LPL activity in the study animals. LPL activity was directly related to LPL mRNA. We conclude that CRF results in marked down-regulation of LPL expression that can contribute to dyslipidemia and altered energy metabolism in uremia. The effect of depressed LPL expression is compounded by the previously demonstrated elevations in uremic plasma of Apo C-III and pre-beta-HDL, which are potent inhibitors of LPL.
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PMID:Down-regulation of tissue lipoprotein lipase expression in experimental chronic renal failure. 894 76

Recombinant human interleukin-2 (rIL-2) is used to treat refractory cancers. During such treatment, patients develop severe hypocholesterolemia along with striking alterations in the concentration and composition of the circulating lipoproteins. The present study was undertaken to gather information about the pathogenesis of these abnormalities. Patients were studied before-, during- and after a 5-day course of high dose i.v. rIL-2. Whole plasma cholesterol was markedly reduced by rIL-2 administration (52%; P < 0.001), whereas the triglyceride concentration did not change. Thus, the lipoproteins became triglyceride enriched (P = 0.004). Low density lipoprotein cholesterol, apolipoprotein B (apoB), high density lipoprotein cholesterol, and apoA-I concentrations all decreased. Esterified cholesterol levels were markedly reduced. Total plasma apoE increased markedly, and two kinds of abnormal particles appeared: 1) beta-migrating, very low density lipoproteins; and 2) discoidal, apoE- and phospholipid-containing particles with abnormal density and electrophoretic mobility. The activities of two lipoprotein triglyceride hydrolases, lipoprotein lipase and hepatic lipase, fell significantly during treatment and returned promptly to pretreatment levels after rIL-2 was discontinued. Lecithin:cholesteryl acyltransferase (LCAT) activity also decreased significantly (64%) during treatment, but in contrast to the lipases, remained low for at least 5 days after the last dose of rIL-2 (P < 0.001). High dose i.v. rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases and acute LCAT deficiency. Most, if not all, of the lipoprotein changes observed are explained by the LCAT deficiency that follows IL-2-induced hepatocellular injury and cholestasis.
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PMID:Acute dyslipoproteinemia induced by interleukin-2: lecithin:cholesteryl acyltransferase, lipoprotein lipase, and hepatic lipase deficiencies. 914 52

Familial combined hyperlipidemia (FCHL) is characterized by different lipid phenotypes (IIa, IIb, IV) and elevated apolipoprotein B (apo B) levels in affected family members. Despite intensive research, the genes involved in the expression of this complex disorder have not been identified, probably because of problems associated with phenotype definition, unknown mode of inheritance, and most probably genetic heterogeneity. To explore the genetics of FCHL in the genetically homogeneous Finnish population, we collected 14 well-documented Finnish pedigrees with premature coronary heart disease and FCHL-like dyslipidemia. The lipolytic enzymes lipoprotein lipase (LPL), hepatic lipase (HL), and hormone-sensitive lipase (HSL) were selected as initial candidate genes because of their central roles in apo B and triglyceride metabolism. On the basis of the pedigree structures, a dominant mode of inheritance was adopted for linkage analyses, and serum total cholesterol and/or triglyceride levels exceeding the 90th percentile level were set as diagnostic criteria (criterion 1). In pairwise linkage analyses with intragenic markers, no evidence for linkage was found. Instead, the significantly negative LOD scores suggested exclusion of all three loci for single major gene effect. LOD scores were -14.63, -5.03, and -5.70 for the three LPL polymorphisms (theta=0.00); -9.40, -6.30, and -4.74 for the three HL polymorphisms (theta=0.00); and -15.29 for the HSL polymorphism (theta=0.00). The results were very similar when apo B levels over the 90th percentile were used as criteria for affected status (criterion 2). Also, when linkage calculations were carried out using an intermediate or recessive mode of inheritance, the results of pairwise linkage analysis remained negative. Furthermore, when haplotypes were constructed from multiple polymorphisms of the LPL and HL genes, no segregation with the FCHL phenotype could be observed in the 14 Finnish families. Data obtained by the affected sib-pair method supported these findings, suggesting that the LPL, HL, or HSL genes do not represent major loci influencing the expression of the FCHL phenotype.
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PMID:No evidence of linkage between familial combined hyperlipidemia and genes encoding lipolytic enzymes in Finnish families. 915 46

Women with polycystic ovary syndrome (PCOS) appear at increased cardiovascular risk due in part to a dyslipidemia characterized by increased plasma triglyceride and reduced high density lipoprotein (HDL) cholesterol levels. This is a detailed exploratory study of HDL composition in 35 obese [body mass index (BMI), > 27] and 22 nonobese subjects with PCOS and in 14 healthy obese and 18 nonobese women. Although we found reduced levels of total and HDL2 cholesterol in obese women with PCOS, HDL composition was modified by depletion of lipid relative to protein, with reduced ratios of HDL total cholesterol and HDL phospholipids to apolipoprotein A-I (apoA-I) compared to those in obese controls (P = 0.008 and P = 0.012, respectively). This was explained by reduced cholesterol (P = 0.004) and phospholipid (although not significant, P = 0.07) in HDL with no change in the content of apoA-I, its major protein. Obesity, insulin resistance, and hyperandrogenemia are features of PCOS and potentially affect lipid metabolism. Insulin sensitivity was assessed by the reduction in endogenous glucose concentration after exogenous insulin; the insulin, glucose, and fatty acid responses to oral glucose; and the fasting insulin concentration. When age, BMI, free androgen index, insulin sensitivity determined by all methods, and the presence of PCOS were subjected to stepwise multivariate regression analysis, the presence of PCOS was the most consistent predictor of lipid-depleted HDL (HDL total cholesterol/apoA-I and HDL phospholipids/apoA-I). We speculate that altered activity of hepatic lipase or lipid transfer protein could explain this aspect of the dyslipidemia. Obesity has an important influence on the lipid profile. Obese PCOS and control subjects had higher levels of cholesterol, triglyceride, apoB, and fatty acids than their lean counterparts, and BMI proved the best predictor of blood levels on multiple regression analysis. In contrast, lean PCOS patients had normal sensitivity to insulin and lipid profiles similar to those of the lean controls and did not manifest the HDL abnormalities. Although in PCOS, correlations were obtained between the free androgen index and cholesterol, triglyceride, and apoB levels and between the integrated glucose and insulin responses after oral glucose and fasting fatty acid and triglyceride levels, when age and adiposity were included as covariates only fatty acids and the integrated glucose response remained significantly correlated. Among the controls, total, low density lipoprotein cholesterol, triglycerides, and apoB were related to aspects of insulin sensitivity independent of age and BMI. Lipid metabolism in PCOS is dependent on several related factors, but subjects with PCOS who are obese show a specific reduction in HDL lipid, suggesting a reduced capacity for cholesterol removal from tissues with diminished antiatherogenic potential. Efforts should be directed toward reducing obesity in PCOS to improve the metabolic disturbance in addition to ameliorating the presenting symptoms.
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PMID:Altered composition of high density lipoproteins in women with the polycystic ovary syndrome. 932 74

Catecholamines are the only hormones with pronounced lipolytic action in man. A number of in vivo and in vitro studies suggest that there is lipolytic resistance to catecholamines in subcutaneous adipose tissue, which is the major fat depot in obese subjects. This is due to multiple alterations in catecholamine signal transduction, involving decreased expression and function of beta2-adrenoceptors, increased function of alpha2-adrenoceptors and decreased ability of cyclic monophosphate (AMP) to stimulate hormone sensitive lipase. A sedentary life-style, which usually characterizes obesity, may contribute to the catecholamine resistance. However, hereditary/genetic factors may also be involved. Recently, decreased expression and function of hormone sensitive lipase has been found in subcutaneous adipocytes of non-obese subjects with heredity for obesity. In addition, polymorphisms in the genes for beta2-adrenoceptors, beta3-adrenoceptors and hormone sensitive lipase, associate with obesity. On the other hand, catecholamine-induced lipolysis in visceral adipose tissue is increased in obesity due to increased function of beta3-adrenoceptors (major finding), decreased function of alpha2-adrenoceptors and increased ability of cyclic AMP to stimulate lipolysis. When the findings in different adipose regions are considered together, it appears that there is a redistribution of lipolysis and thereby fatty acid mobilization in obesity, favouring the visceral fat depot. This leads to an increase in the circulating fatty acid levels in the portal vein, which connects visceral fat with the liver. As a consequence, the liver function may be altered leading to hyperinsulinemia, hyperglycemia and dyslipidemia, which usually accompany the obese state.
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PMID:Catecholamine-induced lipolysis in obesity. 1019 56

Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk.
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PMID:Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients. 1021 33


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