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)

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromatography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or section, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.
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PMID:Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids. 874 May 80

1. The best way to prevent early growth failure in children with renal disease is by the use of specified nutrition and appropriate buffer, activated vitamin D, and calcium-containing phosphate binders as needed. With prenatal diagnosis of anatomically abnormal kidneys available, this type of early intervention may be much more feasible in the 1990s. 2. Supplemental sodium and water in children with polyuria and intravascular volume depletion may prevent growth failure. Cow milk is detrimental in this group of individuals because of high solute and protein load, often causing intravascular volume depletion, hyperphosphatemia, and acidosis. 3. Children with acquired glomerular disease may need sodium restriction and, if treated with steroids, a diet low in saturated fat. 4. Children with nephrotic syndrome and severe edema should be evaluated for malabsorption and subsequent malnutrition. Protein intake should be supplemented only at the RDA and to replace ongoing losses. Long-term sodium restriction is appropriate. Hyperlipidemia should be monitored: if nephrosis is chronic, a low saturated fat diet should be instituted. Angiotensin-converting enzyme inhibitors can decrease urinary protein loss and may ameliorate hyperlipidemia. Children resistant to therapy can have very high morbidity. 5. Children with <50 % of normal creatinine clearance should have PTH measured and activated vitamin D therapy should be started if PTH is elevated more than two to three times normal. Thereafter careful monitoring of calcium, phosphorus, and PTH is crucial to prevent renal osteodystrophy, low turnover bone disease, and hypercalcemia with hypercalciuria and nephrocalcinosis. 6. Children with tubular defects with severe polyuria also may benefit from low-solute, high-volume feedings. 7. All physicians caring for children with renal disease should have pediatric nephrology consultation available. Prevention of growth failure is much more cost effective than pharmacologic therapy. Before initiating growth hormone treatment for growth retardation, assiduous treatment of co-existing renal osteodystrophy and provision of optimal nutritional intake should be accomplished.
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PMID:Nutritional management of the child with mild to moderate chronic renal failure. 876 44

The increasing prevalence and far-reaching medical, social, and economical implications of obesity have made it a national health-care crisis in the United States. About one in every three persons is at least 20% above "ideal" body weight, and approximately 5% have direct weight-related serious health problems (morbid obesity), including hypertension, hyperlipidemia, coronary artery disease, adult-onset diabetes mellitus, degenerative osteoarthropathy, and obstructive sleep apnea. Morbidly obese patients have an estimated 6- to 12-fold increase in mortality. In addition, they have a substantially diminished quality of life, not only physically but also psychosocially due to overt and occult prejudice. Weight reduction must be aggressively pursued in these patients. Medically supervised weight-control programs have been ineffective because patients cannot maintain pronounced long-term weight loss. In contrast, current operative methods have been proved to be effective in helping patients achieve and maintain permanent weight reduction. Several operations have been designed and assessed; with these procedures, weight loss is achieved by inducing malabsorption, maldigestion, early satiety, or a combination of these outcomes. Although these operations have associated side effects and limitations, the expected benefits outweigh the risks. For optimal results, patients must be carefully selected and treated by a multidisciplinary group.
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PMID:Surgical treatment of obesity: who is an appropriate candidate? 917 40

The success of vertical banded gastroplasty (VBG) in the obese transplanted population is measured by a low operative morbidity and mortality in the context of a good record of permanent weight loss and an enhanced quality of life. Selection of transplanted patients for gastroplasty should be guided by the prevailing standards for the general population. VBG is the procedure of choice because of proven efficacy and has the benefit over gastric bypass of not producing malabsorption. The operation causes early satiety while allowing consistent absorption of immunosuppressive medication from the upper gastrointestinal tract, essential in these patients. This risk of hypertension, diabetes mellitus, hyperlipidemia, and immunosuppressive medication toxicity may be decreased by substantial long-term weight loss afforded morbidly obese transplant patients by gastric restrictive surgery. Cardiac risk factors associated with morbid obesity and immunosuppressive therapy are lessened with sustained weight reduction.
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PMID:Gastroplasty for Morbid Obesity after Cardiac and Renal Transplantation. 1077 50

Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.
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PMID:Orlistat in the treatment of obesity. 2694 9

Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 +/- 8 [mean +/- SD] kg x m(-2)) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet (n = 9). At 6 months, BPD had caused the loss of 33 +/- 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 +/- 8 kg x m(-2)), insulin resistance (23 +/- 3 micromol/min per kg of fat-free mass; P < 0.001 vs. 53 +/- 13 of control subjects) was fully reversed (52 +/- 11 micromol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular-but not perivascular or interfibrillar-lipid accumulation decreased (1.63 +/- 1.06 to 0.22 +/- 0.44 score units; P < 0.01; NS vs. 0.07 +/- 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 +/- 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.
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PMID:Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. 1175 34

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

Statins effectively inhibit cholesterol synthesis and are currently the most commonly used drugs for the treatment of hypercholesterolemia. However, patients with familial hypercholesterolemia and those unwilling to take, or who cannot tolerate statins, and patients with combined hyperlipidemia require a combination treatment. Statins combined with cholesterol malabsorption, caused, e.g., by plant stanol esters or ezetimibe (Schering-Plough Corp/Merck & Co Inc), or with bile acid malabsorption, caused by bile acid binding resins or guar gum, inhibit compensatory increases in cholesterol synthesis and effectively lower LDL cholesterol levels. Combination therapy of statins with fibrates should be controlled by lipidology experts. Recent information on indications and advantages of combining statins with n-3 fatty acids, hormone replacement therapy, or niacin, will also be discussed.
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PMID:Combination therapy with statins. 1249 7

Obesity is a life-long, progressive, life-threatening, genetically related, costly, multifactorial disease manifested by excessive fat storage. It is often accompanied by multiple comorbidities including mainly hypertension, diabetes, hyperlipidemia, hypoventilation, obstructive sleep apnea, degenerative arthritis and psychosocial impairment which influence the patients quality of life and ultimately limit their life expectancy. Conservative treatment of morbid and extreme obesity including diet, physical activity, behaviour modifications or pharmacotherapy is not effective in achieving a medically significant long-term weight loss. The costs of such therapy often exceed the costs of the surgical procedure. Surgical treatment of obesity was initiated over 50 years ago. Then the surgical methods were to lead to an increased excretion but finally did not prove useful. They were replaced by restrictive and malabsorption procedures. The first methods including vertical banded gastroplasty (VBG) were introduced in 1982 while gastric banding in 1985. The second method including gastric bypasses or biliopancreatic diversion were implemented in the years 1966-1986. There are also some methods joining these two techniques. Nowadays as a results of minimally invasive surgery development, most of the operations can be performed laparoscopically.
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PMID:[Obesity and surgery]. 1292 68

Antiretroviral regimens are complicated and difficult for patients to follow, and they can have serious side effects, such as osteonecrosis and bone demineralization. Protease inhibitor therapy has been associated with hyperlipidemia, hyperglycemia, gastrointestinal symptoms, and body-fat distribution abnormalities. Nonnucleoside reverse transcriptase inhibitors can cause rashes and hepatotoxicity, and nucleoside reverse transcriptase inhibitors can cause lactic acidosis, hypersensitivity reactions, neuropathies, pancreatitis, anemia, and neutropenia. Malabsorption can occur if antiretroviral agents are taken improperly with regard to meals or if they are taken with certain other drugs or herbal remedies. Some commonly prescribed drugs can cause dangerous drug toxicities if they are taken by patients who are also taking certain antiretroviral medications. Suboptimal exposure to antiretrovirals because of noncompliance or malabsorption can result in viral resistance and loss of future treatment options.
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PMID:Managing issues related to antiretroviral therapy. 1295 84


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