Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotinic acid (niacin) is a water-soluble vitamin widely used for the treatment of lipid disorders. In pharmacologic doses (1 g or more/day), alone or in combination with other lipid-lowering drugs, nicotinic acid lowers very low-density (VLDL) and low-density lipoprotein (LDL) levels, while concurrently increasing high-density lipoprotein (HDL) levels. It may reduce long-term mortality in patients with known coronary artery disease and may slow or reverse the progression of atherosclerosis. A major consideration against using nicotinic acid is the occurrence of frequent, bothersome, adverse reactions such as cutaneous flushing, skin rash, and gastric upset. Careful dosing titration may, however, minimize these effects. The beneficial effects, taken together with the low cost of nicotinic acid therapy and the relative freedom from serious side effects, have made nicotinic acid the agent of choice for the treatment of many patients with hyperlipidemia.
 ...
PMID:Nicotinic acid: a review of its clinical use in the treatment of lipid disorders. 267 60

Modern views of the pathogenesis and natural history of nephrotic syndrome have changed substantially since the early studies by Cotugno and Bright. Contrary to beliefs held 20 years ago, we do not possess a unique satisfying explanation for the induction, maintenance, and resolution of nephrotic edema, and many concepts firmly established as "classic" are now being revised or reconsidered. These include the relationship between urinary protein losses and hypoalbuminemia, which is complicated by several factors such as daily protein intake, albumin catabolism, and the possible role of albumin loss at extrarenal sites. The influence of lowered plasma albumin on the decrease in plasma volume is also quite complex, due to technical difficulties in measuring plasma volume and turnover of radio-labeled albumin. The most contentious areas are how sodium and water retention are initiated and maintained and the relationship between hypoalbuminemia, plasma oncotic pressure, and edema. While aldosterone excretion and plasma concentrations are elevated in nephrotic patients, data on the renin-angiotensin system are controversial and the renal handling of sodium is related to a host of factors including glomerular filtration rate, altered proximal tubular reabsorption, and the role of vasodilators or vasoconstrictors. The complications of nephrotic syndrome are protean and relatively common. Among those are acute renal failure, thrombosis, infections, and hyperlipidemia. Since the introduction of percutaneous biopsy, the spectrum of lesions underlying nephrotic syndrome has widened considerably, the most common being minimal change, especially in children. There are very few prognostic indicators by which response to treatment may be predicted and these include persistent microscopic hematuria.
 ...
PMID:The nephrotic syndrome and its complications. 330 94

In separate experiments, we fed 30 male and 25 female baboons a diet enriched in cholesterol and saturated fat for periods of 3.3 and 2.6 years. Using operant conditioning with water rewards, we trained the animals to puff on smoking machines in a human-like manner. Half of the animals smoked more than 40 cigarettes per day, while the remaining animals (controls) puffed air. Initially, the diet produced twofold (males) and threefold (females) elevations from baseline levels in serum cholesterol concentrations, but over the course of the experiments, the serum cholesterol decreased to 1.5 (males) and 2.0 (females) times baseline levels in both cigarette smokers and controls. Blood carbon monoxide concentration, plasma thiocyanate concentration, and urine cotinine concentration were significantly greater in smokers than in controls. Responses to smoking in males included lymphocytosis, elevated fasting blood glucose concentration, and decreased seminal vesicle weight. In females, hemoglobin and mean corpuscular hemoglobin concentrations were elevated. The extent of atherosclerosis was examined after 2.8 (males) and 1.6 (females) years of smoking. Among males, the extent of lesions in carotid arteries was significantly greater in smokers than in controls, but there were no significant differences in atherosclerosis in the aorta or the brachial, iliac-femoral, or coronary arteries. Among females, there were no significant differences in atherosclerosis between smokers and controls in any artery. These experiments show little effect of 2 to 3 years of cigarette smoke inhalation and concurrent modest elevation of blood carboxyhemoglobin on experimental atherosclerosis in the presence of moderate hyperlipidemia.
 ...
PMID:Cigarette smoking, dietary hyperlipidemia, and experimental atherosclerosis in the baboon. 333 49

The glomerulus is a complex structure containing a remarkable capillary bed which is freely permeable to water and solutes up to the size of inulin. Many small proteins are filtered, reabsorbed, and catabolized by the kidney; but most large proteins, such as albumin or immunoglobulins, are almost entirely excluded from the glomerular ultrafiltrate due to the charge-size permselectivity of the glomerular capillary basement membrane. These large proteins appear in the urine when diseases reduce the charge selectivity or result in the development of large pores in this membrane. The reabsorptive capacity of the renal tubules for these proteins is overwhelmed. Hypoalbuminemia results when increased synthetic and decreased catabolic rates of albumin fail to compensate for the urinary loss of the protein. The resulting decrease in serum oncotic pressure increases the flux of fluid out of systemic capillaries into the interstitial space, a process that increases lymphatic flow and returns the relatively protein-poor ultrafiltrate to the plasma compartment. Interstitial proteins are swept into the plasma by the increased lymphatic flow, leading to a depletion of the extravascular pool of albumin even more severe than the depletion of albumin in the plasma compartment. The rate of albumin synthesis is increased but not sufficiently to replace losses and restore the serum concentration to normal. The rate of albumin catabolism is decreased. This decrease from the normal catabolic rate is as important as the increased rate of albumin synthesis in maintenance of albumin homeostasis in nephrosis. Whereas the reduced serum oncotic pressure certainly contributes to edema formation, sodium retention may result from processes intrinsic to the kidney itself; and plasma volume may actually be expanded despite hypoalbuminemia. The hyperlipemia that occurs in nephrosis is due to a combined defect in lipoprotein metabolism: increased hepatic synthesis of VLDL and decreased removal of TG and highly atherogenic remnants of incompletely metabolized CMs. The defects in lipoprotein metabolism may in part be the end result of the urinary loss of highly negative-charged macromolecules of the mucopolysaccharide called orosomucoid, which carries with it heparan sulfate, and important cofactor for LPL.
 ...
PMID:Mechanisms and consequences of proteinuria. 351 85

The hyperlipidemia accompanying infection has been attributed to production of tumor necrosis factor. This cytokine inhibits adipose tissue lipoprotein lipase, which could decrease clearance of lipoproteins. Infections also increase hepatic lipogenesis. We now have demonstrated that tumor necrosis factor-alpha stimulates lipid synthesis in vivo. 2 h after administration of tumor necrosis factor (25 micrograms/200 g), plasma triglycerides increase 2.2-fold and remain elevated for 17 h. Plasma cholesterol also increases, but this effect appears after 7 h. Tumor necrosis factor rapidly stimulates incorporation of tritiated water into fatty acids in the liver (1-2 h), which persists for 17 h. Also, tumor necrosis factor stimulates hepatic sterol synthesis. Of note, tumor necrosis factor treatment does not stimulate lipid synthesis in other tissues, including adipose tissue. Labeled fatty acids rapidly increase in the plasma, raising the possibility that stimulation of hepatic lipogenesis by tumor necrosis factor contributes to the hyperlipidemia of infection.
 ...
PMID:Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo. 359 72

The association of obesity and hyperlipidemia does not mean that fatness per se is the primary determinant of the lipid abnormality. To evaluate the contribution of fatness to fasting levels of serum triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), we analyzed data on 368 caucasian adults (286 women, 82 men) consecutively entering a weight control program. Although most subjects were overweight, the population represented a wide spectrum of body weights and lipid levels. Study variables included body fat mass (by total body water), fat free mass (FFM), body build (chest to height ratio), fat cell size and number (from bilateral buttock biopsy specimens), upper-lower body fat pattern by arm to thigh circumference ratio, central-peripheral fat pattern by subcapsular to triceps skinfold ratio, waist to hip ratio, and the presence or absence of diabetes. Our results concurred with previously noted correlations of body weight with TG (r = 0.29, P less than 0.0001) and with HDL-C (r = -0.28, P less than 0.0001) at least in the larger sample of women, but there was no significant correlation with LDL-C (r = -0.06). In order to evaluate the relative contribution of the various components of body composition and fat distribution to lipid levels, stepwise regression analyses were performed on the subgroups of women and men. Among women: TG level was predicted best by FFM, upper body fat pattern, age, and diabetes (explaining 30 percent of TG variance); LDL-C level was predicted by age only (explaining 12 percent of variance); and HDL-C level was predicted by body build only (8 percent). Among men: TG level was predicted best by central and upper body fat patterns and diabetes (31 percent of variance); LDL-C and HDL-C levels were not significantly predicted by any of the 11 study variables. These results, obtained from cross-sectional analysis of a predominantly obese sample, suggest that lipid levels may be more directly related to body fat pattern, fat free mass and body build than to body fatness itself.
 ...
PMID:Obesity and serum lipids: an evaluation of the relative contribution of body fat and fat distribution to lipid levels. 361 Apr 68

Dichloroacetate (DCA) reduces blood glucose, lactate and lipids in diabetes or during fasting. Chronic use of DCA, however, is limited by toxicity, probably due in part to its rapid conversion to oxalate in vivo. In theory, therefore, DCA's efficacy may be retained and its toxicity minimized by controlling its rate of metabolism. We attempted to alter DCA pharmacokinetics and bioavailability by synthesizing various derivatives comprising DCA esters with polyols and DCA ionic complexes. Twenty-four hour fasted, nondiabetic rats received single, orogastric doses of saline (control) sodium DCA (100mg/kg) or the following derivatives (D1-4): the esters D1-D3: potassium tetra (dichloroacetyl) glucuronate (D1), inositol-monophosphate-tetradichloroacetate (D2), inositol-hexadichloroacetate (D3) and inositol-hexa [N-methylnicotinate] hexadichloroacetate salt (D4). Each derivative was administered at a dose that would ultimately provide 100 mg/kg DCA as the anion. All derivatives were orally effective in significantly decreasing blood glucose and lactate. D4 exerted the most potent and long-lasting glucose- and lactate-lowering effects, yet increased plasma DCA concentrations less than an equivalent dose of the sodium salt. When administered to reverse light-cycled rats, D4 markedly inhibited the incorporation of tritiated water into cholesterol and triglycerides. We conclude that derivatives of DCA retain the biological activity of the parent compound, but may exhibit different pharmacokinetics. They may eventually prove useful in the treatment of diabetes mellitus, hyperlipidemia and lactic acidosis in man.
 ...
PMID:Dichloroacetate derivatives. Metabolic effects and pharmacodynamics in normal rats. 366 16

Sodium nitrite administered in the drinking water to Long-Evans rats during pregnancy and lactation severely affected erythropoietic development, growth, and mortality in their offspring. Pregnant rats were maintained throughout gestation on 0.5, 1, 2, or 3 g NaNO2/liter. There were no significant differences between treated and control litters at birth. Thereafter, pups of treated dams on 2 and 3 g NaNO2/liter gained less weight, progressively became severely anemic, and began to die by the third week postpartum. By the second week postpartum, hemoglobin levels, RBC counts, and mean corpuscular volumes of these pups were all drastically reduced compared to controls. Blood smears showed marked anisocytosis and hypochromasia. Gross chylous serum lipemia and fatty liver degeneration were noted. Histopathology demonstrated cytoplasmic vacuolization of centrilobular hepatocytes and decreased hematopoiesis in bone marrow and spleen. Administration of 1 g NaNO2/liter resulted in hematological effects but did not affect growth or mortality. NaNO2 (0.5 g/liter) was at or near the no observed effect level. Cross-fostering indicated that treatment during the lactational period was more instrumental in producing lesions than treatment during the gestational period. The data presented are consistent with the lactational induction of severe iron deficiency in the neonate.
 ...
PMID:Evaluation of the developmental toxicity of sodium nitrite in Long-Evans rats. 369 23

In 260 male farmers (40-45 years) divided into 9 groups from different areas in France and Britain, coagulation, platelet aggregation, lipemia, fatty acids from plasma lipids and platelet phospholipids were determined in relation to the food intake evaluated by recall, weighing and chemical analysis of the diet. The clotting activity of platelets and their response to thrombin aggregation was significantly correlated on an individual basis with the intake of saturated fatty acids both in subsamples as well as in the whole study. Serum cholesterol was also significantly correlated with saturated fats but only on a group basis or on the totality of the study. Calcium, linolenic acid and alcohol in the diet were inversely related to certain platelet functions. Linoleic acid was inversely related to serum cholesterol and triglycerides. Dietary saturated fats were associated, with an increase in the platelet phospholipids not in saturated fatty acids but in 20:3 (n-9), known to promote platelet aggregation to thrombin, with a decrease in platelet cholesterol, also apparently regulating platelet functions. The present studies indicate that dietary saturated fats, calcium (hard water) and alcohol, influence platelet behaviour in a way strictly parallel to their known effect on coronary heart disease.
 ...
PMID:Nutrients, platelet function and composition in nine groups of French and British farmers. 370 72

The optical aberrations due to the presence of the turbidity caused by hyperlipidemia has been eliminated in two serum glucose procedures. This has been accomplished by incorporating lipase and alpha-cyclodextrin into the two glucose reagents. The hydrolytic action of the lipase generates water soluble glycerol and insoluble fatty acids. By including the chemical scavenger alpha-cyclodextrin into the reagent the fatty acids are solubilized and thus the production of a second turbidity is avoided. Because the clearing reagents are incorporated into the glucose reagents, this is an on-line process and no additional labor is required to clear the sample-reagent mixture. Furthermore, no additional time is required as the clearing occurs in the same period of time that it takes for the indicator reactions to reach equilibrium.
 ...
PMID:On-line clarification for the measurement of serum glucose in hyperlipidemic specimens. 370 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>