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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of different routes and modes of administration of niacin (nicotinic acid) on its hypolipidaemic activity has been evaluated. Our working hypothesis was that the major sites of niacin action are located presystemically (i.e. in the gut wall or the liver, or both) which would make niacin a gastrointestinal drug. For such drugs continuous administration to the gastrointestinal tract is expected to augment their efficacy compared with bolus oral administration or parenteral administration. The hypothesis was examined in two rat models of experimentally induced hyperlipidaemia-Model A, based on a cholesterol-enriched diet, and Model B, in which acute hyperlipidaemia is induced by intraperitoneal administration of triton (225 mg kg(-1)). Continuous administration of niacin into the duodenum at 1.66 mg h(-1) (total dose 40 mg kg(-1) day(-1)) for up to 7 days (Model A) or at 2.22 mg h(-1) over 18 h (Model B) had significantly greater lipid-reducing effects both on total cholesterol and on triglyceride levels (15-25%) and elevation of high-density lipoprotein (HDL) cholesterol levels than did bolus oral administration of the same dose. Continuous duodenal infusion of niacin also had an even greater lipid-reducing effect than continuous intravenous infusion of the drug at the same rate and dose. The results indicate that the site(s) of action are located presystemically and that continuous duodenal administration of a low dose of niacin (40 mg kg(-1)) has a greater lipid-lowering effect than a higher dose (200 mg kg(-1)) administered by peroral bolus administration. These conclusions were validated by administration of a specially designed niacin sustained-release matrix tablet formulation that was non-invasively administered to hyperlipidaemic rats. The hypolipidaemic activity of the sustained-release tablet was of similar magnitude to that resulting from continuous duodenal administration, thus providing a pharmacodynamic rationale for this mode of administration.
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PMID:The effect of the mode of administration on the hypolipidaemic activity of niacin: continuous gastrointestinal administration of low-dose niacin improves lipid-lowering efficacy in experimentally-induced hyperlipidaemic rats. 987 8

This article reviews the nutritional requirements of puberty and the clinical assessment of nutritional status, and discusses the nutritional risks imposed by vegetarian diets, pregnancy, and athletic involvement. Energy (calories) and protein are essential in pubertal development. Adolescent females require approximately 2200 calories/day, whereas male adolescents require 2500-3000 calories/day. Additional intake requirements include fat, calcium, iron, zinc, vitamins, and fiber. The clinical assessment of nutritional status begins with obtaining a good diet history of the patient and this could be offered by the body mass index. Nutritional deficiencies and poor eating habits established during adolescence can have long-term consequences, including delayed sexual maturation, loss of final adult height, osteoporosis, hyperlipidemia, and obesity. As for vegetarian adolescents, nutritional risks include lack of iodine, vitamin B12, vitamin D, and some essential fatty acids. In addition, substances in some grains reduce gut absorption, thus increasing mineral deficiencies. Pregnancy may also be a risk factor for poor nutrition during adolescence. A pregnant adolescent has different nutritional needs because she is still growing. Among adolescent athletes many are turning to nutritional supplements in an attempt to improve athletic performance. A balanced, varied diet provides adequate calories and nutrition to meet the needs of most adolescents. They also have greater water needs than do adult athletes. Details on adolescent health concerns are further discussed in this article.
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PMID:Nutrition in the adolescent. 1003 86

Postprandial hyperlipidemia (PH) is recognized as a significant risk factor for cardiovascular disease. The present study, involving rats with streptozotocin (STZ)-induced diabetes, was performed to establish a PH model and to examine the relation between small intestinal acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity and serum lipid levels in the postprandial state. The small intestinal ACAT activities in normal rats during the experimental period were 4 to 5 pmol/mg protein per minute. In contrast, in the diabetic rats, the ACAT activities were 2 to 3 times higher than activities seen in normal rats from 7 to 21 days after the STZ injection in the absence of a high fat diet and hyperplasia in the gut. In an oral fat-loading test that used diabetic rats that had been injected with STZ (60 mg/kg) intravenously 14 days previously, the postloading changes in the serum concentrations of total cholesterol (TC) and triglyceride (TG) were significantly greater in the diabetic rats than in normal rats. Single oral administration of (1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]cyclohexane- 1-yl 3-[(4R)-N-(2,2,5,5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate (F-1394, 3 to 30 mg/kg), a potent ACAT inhibitor, suppressed the post-fat-loading elevation of serum TC levels in the diabetic rats in a dose-dependent manner without affecting serum glucose levels. Furthermore, the small intestinal ACAT activity, serum TG levels, and lymphatic absorption of TC and TG in the rats that were administered F-1394 (30 mg/kg) were reduced by approximately 90%, 70%, 30%, and 15%, respectively. This is the first evidence that elevated ACAT activity in the gut, unlike hyperplasia and hyperphagia, induces PH in rats. Our results strongly suggest that F-1394 may be a potential treatment for PH in humans.
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PMID:Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A:cholesterol acyltransferase activity. 1063 14

Lactobacillus sporogenes is a gram-positive, spore-forming, lactic-acid producing bacillus. It was originally isolated and described in 1933. The organism requires a complex mixture of organic substrates for growth, including fermentable carbohydrates and peptides. It has been used clinically for gut dysbiosis, hyperlipidemia, aphthous stomatitis, and vaginitis.
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PMID:Lactobacillus sporogenes. 1219 86

Injection of insulin causes release of HISS (hepatic insulin sensitizing substance) from the liver in the fed state. HISS action accounts for 50-60% of the glucose disposal produced by a wide range of insulin doses (5-100 mU/kg). Although the chemical nature of HISS is unknown, precluding pharmacokinetic studies, the pharmacodynamics of HISS has advanced because of the use of the rapid insulin sensitivity test (RIST) which is a transient euglycemic clamp used following a bolus of insulin. HISS action can be blocked by hepatic denervation and restored by intraportal but not intravenous infusion of acetylcholine or a nitric oxide donor. HISS release is prevented by blockade of hepatic muscarinic receptors, nitric oxide synthase blockers, indomethacin, and animal models of insulin resistance, including chronic liver disease, sucrose feeding, hypertension, aging, obesity, and fetal alcohol exposure. HISS acts on skeletal muscle but not liver, gut, or adipose tissue. HISS is released by insulin in the fed state but decreases to insignificance after 24-hr fasting in rats. Cats and dogs appear to require a longer period of fasting to prevent HISS action. Lack of HISS action is suggested to be the cause of post-meal hyperglycemia and hyperlipidemia in type 2 diabetes and other disease states with similar metabolic dysfunction. The RIST can be carried out up to six times in the same animal, is not affected by pentobarbital anesthesia, and can readily differentiate HISS-dependent and HISS-independent insulin action.
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PMID:Practice and principles of pharmacodynamic determination of HISS-dependent and HISS-independent insulin action: methods to quantitate mechanisms of insulin resistance. 1242 50

Excess calorie intake in industrialized countries has prompted development of fat substitutes and other lower-calorie dietary items to enhance health. DAG cooking oils, with a 1,3 configuration, taste and have the texture of commonly used TAG cooking oils. Because they are not hydrolyzed to 2-MAG in the gut, the absorption and metabolism of DAG oil differs from that of TAG. Among the physiological differences are lower postprandial lipemia and an increased proportion of FA being oxidized instead of stored. Preliminary studies suggest that these differences in energy partitioning between DAG and TAG may be usefully exploited to reduce the amount of fat stored from cooking oil and oil components of food items. Over 70 million bottles of DAG oil have been sold in Japan since its introduction in February 1999, and the product is being test-marketed in the United States. It is hoped that wider use of DAG oil may provide one additional means of preventing obesity.
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PMID:Nutritional characteristics of DAG oil. 1273 44

Effects of acute and chronic alcohol intake on fasted and postprandial lipemia in the rat model are reported. In the acute study, fasted rats are loaded with a 30% w/w olive oil emulsion with or without 8% alcohol in the form of ethanol, beer or whisky. After 3 h, either mesenteric lymph or blood is collected and the TAG-rich lipoprotein fractions are isolated. In the chronic study, animals received, for a period of 10 weeks, 3% alcohol in drinking water in the form of ethanol, beer or whisky. Blood samples were collected from animals in either the fasted state or after being loaded with the fat load as described above. Alcohol ingestion along with a fat load increases the number (increased net apoB48 secretion) and reduces the size (reduced TAG/apoB48 ratio) of CM secreted into the mesenteric lymph duct. It also delays gastric emptying, reduces trans-enterocyte TAG flux rates and increases plasma concentrations of TAG, cholesterol and CM. Similar conditions also results in increased total phospholipid and cholesterol content of CM but not of VLDL, indicating an enhanced liver bile secretion into the gut; however, a significant increase in plasma VLDL concentration is observed. Unlike the acute study, an alcohol-fat load in animals put on chronic alcohol intake results in increased HDL cholesterol concentrations and less pronounced postprandial hypertriglyceridemia and hypercholesterolemia but not hyperchylomicronemia. In the fasted state, plasma TAG and total apoB concentrations are not modified in these animals, and an increase in HDL and a decrease in total and LDL cholesterol concentrations are observed. No liver function impairment is observed following the 10-week period of chronic alcohol intake. In conclusion, unlike binge drinking, chronic moderate alcohol consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.
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PMID:Effect of acute and chronic moderate alcohol consumption on fasted and postprandial lipemia in the rat. 1296 8

Increased postprandial lipemia is a risk marker of cardiovascular disease (CVD). While moderate alcohol drinking is associated with a reduced risk of CVD in nondiabetic and type 2 diabetic patients, it is also known that alcohol increases postprandial triacylglycerol levels. The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are important hormones from the gut that enhance nutrient-stimulated insulin secretion. Their responses to a moderate alcohol dose in type 2 diabetes have not previously been studied. We sought to determine how alcohol influences postprandial lipid and incretin levels in patients with type 2 diabetes when taken in combination with a fat-rich mixed meal. Eleven patients with type 2 diabetes ingested on 3 separate days in random order 3 different meals containing: 100 g butter alone or 100 g butter in combination with 40 g alcohol and 50 g carbohydrate, or 100 g butter and 120 g carbohydrate. The meal with alcohol and 50 g carbohydrate was isocaloric to that of 120 g carbohydrate. Triacylglycerol levels were measured after separation by ultracentrifugation into a chylomicron-rich fraction with Svedberg flotation unit values (Sf) > 1,000, and a chylomicron-poor fraction with Sf < 1,000. Supplementation of a fat-rich mixed meal with alcohol in type 2 diabetic subjects suppressed GLP-1 early in the postprandial phase and increased the late triacylglycerol responses compared with the 2 other meals. In the chylomicron-rich fraction, both triacylglycerol and cholesterol were increased by alcohol. No significant differences in high-density lipoprotein (HDL)-cholesterol levels were seen. Isocaloric amounts of carbohydrate and alcohol suppressed equally the postprandial free fatty acid levels, but carbohydrate increased the postprandial glucose, GIP, and insulin levels the most. Early in the postprandial phase, alcohol suppresses the incretin responses and increases the late postprandial triacylglycerol levels in type 2 diabetic patients. Whether this reflects an alcohol-induced suppression of the incretin response, which adds to the alcohol-induced impairment of triacylglycerol clearance in type 2 diabetic patients, remains to be elucidated.
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PMID:Ethanol with a mixed meal decreases the incretin levels early postprandially and increases postprandial lipemia in type 2 diabetic patients. 1468 46

For about a century there has been recognition that calcium and lipids bind to one another in the gut, each interfering with the other's absorption. Calcium also causes malabsorption of bile acids, which is likely to contribute further to malabsorption of fat. High dietary calcium intakes may also have stimulatory effects on lipolysis. These mechanisms provide a basis for hypothesising that calcium supplementation may impact on circulating lipid concentrations, and there is now a significant amount of observational and trial data indicating that this is the case. The largest randomised controlled trial of calcium effects on lipids was carried out in 223 healthy postmenopausal women, and found that low density lipoprotein-cholesterol (LDL-C) decreased 6.3% and high density lipoprotein-cholesterol (HDL-C) increased by 7.3% at 1-year. The resultant 16.4% increase in HDL-C/LDL-C ratio would be predicted to reduce cardiovascular event rates by 20-30%, which is consistent with the available observational data. There are no trial data addressing this question and it is possible that other lipid-lowering agents, such as hydroxymethylglutaryl coenzyme A reductase inhibitors, might impact on cardiac event rates by mechanisms other than by lowering cholesterol levels. Therefore, caution is appropriate in incorporating these findings into clinical practice, but the balance of evidence suggests that calcium is a cost-effective adjunct to the dietary management of hyperlipidaemia.
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PMID:Effects of calcium supplementation on circulating lipids: potential pharmacoeconomic implications. 1471 41

The polyol isomalt (Palatinit) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0.03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0.006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. In addition, the study data indicate that isomalt could be useful in improving bowel function.
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PMID:Effects of isomalt consumption on gastrointestinal and metabolic parameters in healthy volunteers. 1619 83


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