Cholesterol in humans

Probucol. Probucol is an antioxidant that is effective in lowering LDL cholesterol. Whereas probucol was known to lower cholesterol after relatively simple clinical trials (160), its mechanism of action as an antioxidant in the treatment of atherosclerosis is quite novel. Probucol has been shown to have the abiUty to produce regression of atherosclerotic lesions in animal models (161). Probucol therefore represents a novel class of pharmaceutical agent for the treatment of atherosclerosis. This effect occurs mechanistically, in part, by preventing oxidation of LDL, a necessary step in foam cell formation. This antioxidant activity has been shown in laboratory experiments and its activity in lowering LDL cholesterol in human studies is well documented (162). 

In Western countries, the total plasma cholesterol in humans is about 5.2 mmol/L, rising with age, though there are wide variations between individuals. The greater part is found in the esterified form. It is transported in hpoproteins of the plasma, and the highest proportion of cholesterol is found in the LDL. Dietary cholesterol equifibrates with plasma cholesterol in days... 

Viard M, Parolini I, Sargiacomo M, et al. Role of cholesterol in human immunodeficiency virus type 1 envelope protein-mediated fusion with host cells. J Virol 2002 76(22) 11584-11595. 

Amphotericin-B is highly toxic as ergosterol is very similar to cholesterol and amphotericin has thus cross-reactivity to cholesterol in human cell membranes. Adverse effects include chills, fever, dyspnea, hepatotoxicity and anemia. However, nephrotoxicity is the most common complication, although adequate hydration can reduce the risk for this toxicity to some extend. Amphotericin induced nephrotoxicity may be irreversible. Liposomal preparations have shown to be therapeutically effective with little or no renal damage. 

Morris, and S. B. Lester. Stabilized rice bran and oat bran lower cholesterol in humans. Nutr Res 1993 13(4) ... 

In 2001, a comparison was undertaken to assess the capability of countries to measure cholesterol in human serum (Welch et al. 2001). After a pilot... 

Regulation of Cholesterol Biosynthesis Cholesterol in humans can be obtained from the diet or synthesized de novo. An adult human on a low-cholesterol diet typically synthesizes 600 mg of cholesterol per day in the liver. If the amount of cholesterol in the diet is large, de novo synthesis of cholesterol is drastically reduced. How is this regulation brought about ... 

Burnett and coworkers have described the synthesis of a very potent class of cholesterol absorption inhibitors (CAI) typified by the original lead compound in this series the compound I showed in Fig. 42 (SCH 48461). This 2-azetidinone has resulted as an effective inhibitor of cholesterol absorption in a cholesterol-fed hamster model [9]. Subsequently, the same molecule has been shown to reduce serum cholesterol in human clinical trials [382]. Although this class of compounds has been initially designed as acyl coenzyme A cholesterol transferases (ACAT) inhibitors, early structure-activity studies demonstrated a striking divergence of in vitro ACAT inhibition and in vivo activity in the cholesterol-fed hamster. A detailed examination of this molecule indicated that the hypocholesterolemic... 

On the basis of these experiments, we anticipated that conformationally constrained analogues of our open chain diamides (1 and 2) may increase activity against cancer cell lines. In (3-lactam chemistry, this kind of hypothesis had been tested, and it was established that certain (3-lactams are more effective at lowering cholesterol in human plasma when compared to open-chain substrates [12-15]. Therefore, preparation of (3-lactams of type 3 and related compounds was necessary to investigate a comparative study with diamides 1 and 2. 

Sarria, A. J., Panini, S. R., and Evans, R. M. (1992). A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells./. Biol. Chem. 267, 19455-19463. 

The determination of cholesterol is important for the diagnosis and prevention of a number of clinical disorders such as hypertension, arteriosclerosis, cerebral thrombosis and coronary heart disease. As the majority of cholesterol in human blood is present in an esterified form, a separate saponification step is required to obtain a total cholesterol analysis early methods for this involved caustic and toxic reagents, long analysis times and a relatively large sample volume. Free cholesterol can be determined chromatographically, although this requires cumbersome and expensive laboratory-based equipment. Modern methods use the enzyme cholesterol esterase to release esterified cholesterol which is then oxidised by a second enzyme, cholesterol oxidase (ChOx, Fig. 23.3) [48]. 

Perez-Urquiza M et al. (2003) Use of reference value for the Proficiency Test scheme in the measurement of glucose and cholesterol in human serum. 

LB Agellon, A Walsh, T Hayek, P Moulin, XC Jiang, SA Shelanski, JL Breslow, AR Tall. Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J Biol Chem 266 10796-10801, 1991. 

The major function of LTP-I in human plasma may be to distribute es-terified cholesterol from the HDL fraction, where cholesterol is esterified, to other lipoprotein fractions. LCAT activity is responsible for the production of some 50-100 nmol esterified cholesterol per milliliter of plasma per hour (Gil). The concentration of esterified cholesterol in human HDL is about 1000 nmol/ml of plasma. Only 0.5-1.0% of HDL apoprotein is removed from plasma per hour (B41), probably mainly in intact HDL particles. If so, then the uptake of HDL particles can account for the removal from plasma of only about 10-20% of the esterified cholesterol formed in HDL in the LCAT reaction. 

K19. Kostner, G., The influence of various lipoproteins and apolipoproteins on the in vitro esterification of cholesterol in human serum by the enzyme lecithimcholesterol acyltransferase. Scand. J. Clin. Lab. Invest. 38 (Suppl. 150), 66-71 (1978). 

Their synthesis and subsequent excretion in the faeces represents the only significant mechanism for the elimination of excess cholesterol. In humans, roughly 500 mg of cholesterol is converted to bile acids and eliminated in bile every day. 

Most, M.M. Tulley, R. Morales, S. Lefevre, M. 2005. Rice bran oil, not fiber, lowers cholesterol in humans. Am. J. Clin. Nutr. 81 64-68. 

The initial interest in rice bran oil resulted from work with the stabilized rice bran. Rice bran was shown to be equivalent in serum cholesterol reduction to oat bran in hamster trials (Table 15) (1). Two clinical studies showed rice bran reduced serum low-density lipoprotein (LDL) cholesterol in humans (49,50). Defatted bran was less effective in lowering cholesterol than full fat bran (1). The cholesterol-lowering activity was concentrated in the unsaponifiable fraction of rice bran oil (Table 16) (51). Oryzanol was found to contribute to the hypocholesterolemic activity of rice... 

An interesting species difference might be pointed out. The above HMG-CoA reductase inhibitors inhibit HMG-CoA reductase from a variety of animals, and reduce serum cholesterol in humans, rabbits and dogs, but do not reduce serum chr lesterol in rats and mice (Sakono et ai, 1996). 

Eahsoluble vitamins, carotenoids, and cholesterol in human serum. ... 

Lipids in frozen human serum (freeze dried) f Cholesterol in human serum (freeze dried)... 

EUerbe P, Myers GL, Cooper GR, Hertz HS, Sniegoski LT, Welch MJ, White Et. A comparison of results for cholesterol in human serum obtained by the Reference Method and by the Definitive Method of the National Reference System for cholesterol. Clin Chem 1990 36 370-5. 

Kritharides L, Jessup W, Mander EL, et al. (1995) Apohpoprotein A-I-mediated efflux of sterols from oxidized LDL-loaded macrophages. Arterioscler ThrombArterioscler Thromb Vase Biol 15 276-289 Kruth HS (1984) Localization of unesterified cholesterol in human atherosclerotic lesions. Demonstration of... 

CYP-inhibiting amines (e.g., SKF 525A) have been used to control elevated levels of cholesterol in humans. They are also toxic to fungi by the same mechanism. SKF 252A has been extensively used as a specific inhibitor of CYP enzymes in research and is a particularly strong inhibitor of CYP51, but has not been used as a commercial fungicide. 

During the more than two decades that pectin research has been carried out, two areas of investigation with potential benefit to human health have been in lipid metabolism (Table II) and carbohydrate metabolism (Table III). Pectin has been shown to decrease serum cholesterol in humans (6-11) as well as other animal species (10). High levels of serum cholesterol are generally considered to be a risk factor associated with ischemic heart disease (11-13). Consumption of pectin to reduce cholesterol levels in the blood might be expected to reduce the incidence of heart disease especially when serum cholesterol is elevated. 

Ketoconazole is a weak inhibitor of enzymatic conversion of lanosterol to cholesterol in humans. 

Taku, K. K. Umegaki Y. Sato Y. Taki K. Endoh S. Watanabe. Soy isoflavones lower serum total and LDL cholesterol in humans A meta-analysis of 11 randomized controlled trials. Am. J. Clin. Nutr. 2007, 85, 1148-1156. 

WollT-Briche, C.S.L., Carter, D. and Webb, K.S. A comparison of GC/MS and LC/MS measurements for high accuracy analysis of cholesterol in human senun by isotope dilution mass spectrometry, Rapid Commun. Mass Spectrom, 16, 848-853 (2002). 

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