Lower My Cholesterol Naturally

Beat Cholesterol Guide

In Beat Cholesterol in 30 Days, Scott Davis, a medical researcher and expert in alternative health (also a former sufferer of cholesterol), lets out his studies-based discoveries for beating high cholesterol levels with no drugs, no dangers involved, and no side effects to worry about. This program reveals to people some main factors that cause their hypercholesterolemia such as smoking, high blood pressure, diabetes, obesity, and family history of heart disease. The program also covers tips to prevent the recurrence of hypercholesterolemia such as eating a low-fat and low-salt diet, stopping smoking, losing extra pounds, and maintaining a healthy weight. In addition to the program you get a few extra bonuses when you download the e-book. You also get 10 recipes to get you started, an appendix with the symptoms of a heart attack, and an appendix of foods that you cant eat. These are a great addition to the rest of the information provided in this e-book. Read more...

Natural Cholesterol Guide Summary

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My Natural Cholesterol Guide Review

Highly Recommended

All of the information that the author discovered has been compiled into a downloadable ebook so that purchasers of Natural Cholesterol Guide can begin putting the methods it teaches to use as soon as possible.

When compared to other ebooks and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

Statins and Cognition

Preliminary enthusiasm in statins and cognition had been tempered by negative findings from two large cardiovascular studies examining the effects of statins on mortality and cardiovascular events where cognition was assessed as a secondary outcome. In 2002, the Foundation Heart Protection study evaluated effectiveness of 40 mg simvastatin in 20,536 elderly adults, including 5,806 between the age of 70-80 years. A telephone interview for cognitive status was used to assess cognition over the 5-year study period, and no differences in cognition was observed between placebo vs. statin treated groups 64 . The second large, Prospective Study of Pravastatin in the Elderly (PROSPER) evaluated pravastatin use in 5804 70-80 year-old cardiovascular patients at risk for dementia for 3.2 years. A number of cognitive tests were assessed including mini mental state exam (MMSE), Stroop and word learning digit recall memory tests. Again, no effect on cognition was noted 65 . The prior results are in...

Drug Therapy For Hypercholesterolemia And Dyslipidemia

Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-associated conditions, such as coronary heart disease (CHD), ischemic cerebrovascular disease, and peripheral vascular disease. These conditions account for most morbidity and mortality among middle-aged and older adults. Dyslipidemias, including hyperlipidemia (hypercholesterolemia) and low levels of high-density-lipoprotein cholesterol (HDL-C), are major causes of increased atherogenesis both genetic disorders and lifestyle (sedentary behavior and diets high in calories, saturated fat, and cholesterol) contribute to the dyslipidemias seen in developed countries.

Bile acid sequestrants

Colesevelam, colestipol, and colestyramine are bile acid sequestrants used in the management of hyper-cholesterolaemia. They act by binding bile acids, preventing their reabsorption this promotes hepatic conversion of cholesterol into bile acids the resultant increased LDL-receptor activity of liver cells increases the clearance of LDL-cholesterol from the plasma. Bile acid sequestrants effectively reduce LDL-cholesterol but can aggravate hypertriglyceridaemia. Cautions Bile acid sequestrants interfere with the absorption of fat-soluble vitamins supplements of vitamins A, D, K, and folic acid may be required when treatment is prolonged. Interactions Appendix 1 (bile acid sequestrants) Pregnancy and breast-feeding Bile acid sequestrants should be used with caution as although the drugs are not absorbed, they may cause fat-soluble vitamin deficiency on prolonged use. Side-effects As bile acid sequestrants are not absorbed, gastro-intestinal side-effects predominate. Constipation is...

Statins and Ap

Cholesterol can impact A 3 synthesis through both direct and indirect mechanisms and it has been hypothesized that statins, as modulators of cholesterol, should decrease A 3 levels. Indeed, statin induced reductions in A 3 have been supported by cell culture studies. Early in vitro models showed 4uM treatment of lovastatin or simvastatin could reduce beta amyloid secretion of cultured cells 74-76 . Results from in vivo models have been mixed. In guinea pigs, high doses of simvastatin decreased brain A 3 75 . Atorvastatin decreased brain A 3 peptide levels in PSAPP mice 77 and pravastatin and lovastatin reduced brain A 3 in TgCRND8 transgenics 78 . In non-transgenic mice, simvastatin, lovastatin, and atorvastatin all reduced A 3 peptide levels 56 . However, statin effects in transgenic models are not uniform across the board, and other labs have reported increased brain A 3 in Tg2576 females following lovastatin treatment 79 . lovastatin elevated sAPPalpha in TgCRNDA mice 78 , while...

Colestyramine

(Cholestyramine) Indications pruritus associated with partial biliary obstruction and primary biliary cirrhosis diarrhoea associated with Crohn's disease, ileal resection, vagotomy, diabetic vagal neuropathy, and radiation hypercholesterolaemia (section 2.12) Cautions section 2.12 Contra-indications section 2.12 Pregnancy section 2.12 Breast-feeding section 2.12 Side-effects section 2.12 Dose divided doses, then adjusted as required max. 36 g daily CHILD 1-18 years see BNF for Children Counselling Other drugs should be taken at least 1 hour before or 4-6 hours after colestyramine to reduce possible interference with absorption

M Colestyramine

(Cholestyramine) Indications hyperlipidaemias, particularly type Ila, in patients who have not responded adequately to diet and other appropriate measures primary prevention of coronary heart disease in men aged 35-59 years with primary hypercholesterolaemia who have not responded to diet and other appropriate measures (colestyramine) Contra-indications complete biliary obstruction (not Colestyramine (Non-proprietary) A Powder, sugar-free, colestyramine (anhydrous) 4g sachet, net price 50-sachet pack 18.34. Label 13, counselling, avoid other drugs at same time (see notes above) Questran (Bristol-Myers Squibb) A Powder, colestyramine (anhydrous) 4g sachet, net price 50-sachet pack 10.76. Label 13, counselling, avoid other drugs at same time (see notes above) Questran Light (Bristol-Myers Squibb) A Powder, sugar-free, colestyramine (anhydrous) 4 g sachet, net price 50-sachet pack 16.15. Label 13, counselling, avoid other drugs at same time (see notes above)

Statins

The statins (atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin) competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol synthesis, especially in the liver. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration but they are less effective than the fibrates in reducing triglyceride concentration. However, statins reduce cardiovascular disease events and total mortality irrespective of the initial cholesterol concentration. Statins should be considered for all patients, including the elderly, with symptomatic cardiovascular disease such as those with coronary heart disease (including history of angina or acute myocardial infarction), occlusive arterial disease (including peripheral vascular disease, non-haemorrhagic stroke, or transient ischaemic attacks). In patients with diabetes mellitus, the risk of developing cardiovascular disease depends on the duration...

Functional Foods And Disease Prevention

Further, soy protein inclusions are getting highly recognized by women population due to their ability to reduce the risk of heart diseases by lowering blood cholesterol levels, promoting bone health, and easing symptoms of menopause. Further, there is an increasing demand for products targeting children. Active ingredients are added in these products and are capable of supporting brain development of infants, immunity enhancement, and acting against allergy reactions in the body. Also some of these products are aiming at promoting healthier eating habits and active life styles among children to prevent the unprecedented growth of obesity and related complications. Functional protein, peptides, and amino acids from different food sources are also renowned, and among them, soy protein concentrates are gaining much popularity attributed to the functional properties specifically toward women population. Other than that, there are products that are becoming popular for...

Present Situation And Potential Of Seaweeds For Novel Functional Food Product Developments

Successful functional product innovations dealt with other food sources have been mainly launched targeting the markets for nonalcoholic beverages fortified with the vitamins or other functional ingredients, breakfast cereals, cholesterol-lowering spreads, confectionery, biscuits, cereal, cereal bars, soft drinks, probiotic and prebiotic dairy products, isotonic drinks, bakery, and hypoallergenic baby foods. Further, ever-concerning chronic disease-related conditions such as cancer, high cholesterol, coronary heart diseases, atherosclerosis, stroke, hypertension, diabetes (type II), gastrointestinal disorders, osteoporosis, intestinal complications, and immune disorders including allergy have been used as prime focuses when developing these functional food products. When analyzing the supply structure of these functional foods, the main types of successful actors in the commercial functional food segment are multinational food companies with a broad product range and pharmaceutical or...

Roles Of Aquaporins In Mammalian Physiology Deduced From Phenotypes Of Aqpnull Mice

Hydration and skin elasticity, as well as impaired stratum corneum biosynthesis and wound healing (27). The mechanism responsible for the skin phenotype in AQP3 deficiency involves reduced epidermal cell-skin glycerol permeability, resulting in reduced glycerol content in the stratum corneum and epidermis. Interesting recent data suggest involvement of AQP3 in epidermal-cell proliferation by a mechanism that may involve reduced cellular ATP-content and impaired mitogen-activated protein (MAP) kinase signaling (28). As described below, AQP3-dependent cell proliferation has relevance to repair of the corneal epithelium following injury. Another aquaglyceroporin, AQP7, is expressed in the plasma membrane of adipocytes. Aquaporin 7-null mice have a greater fat-mass than wild-type mice as they age, with remarkable adipocyte hypertrophy and accumulation of glycerol and triglycerides (29). As shown in Fig. 2E, hypertrophy of AQP7-deficient adipocytes probably results from reduced plasma...

Transporters Involved In Pharmacokinetics Hepatic Transporters

Statins are cholesterol-lowering agents that reversibly inhibit HMG-CoA reductase, which catalyzes a rate-limiting step in cholesterol biosynthesis (see Chapter 35). Most of the statins in the acid form are substrates of uptake transporters that mediate hepatic uptake and enterohepatic circulation (Figures 2 5 and 2-6). In this process, hepatic uptake transporters such as OATP1B1 and efflux transporters such as MRP2 cooperate to produce vectorial transcellular transport of bisubstrates in the liver. The efficient first-pass hepatic uptake of statins by OATP1B1 helps them to exert their pharmacological effect and also minimizes the systemic drug distribution, thereby minimizing adverse effects in smooth muscle. Recently, two common SNPs in SLCO1B1 (OATP1B1) have been associated with elevated plasma levels of pravastatin.

Bloodbrain And Bloodcsf Barriers

Drugs acting in the CNS must either cross the BBB or the blood-CSF barrier, which are formed by brain capillary endothelial cells or epithelial cells of the choroid plexus, respectively. Efflux transporters play a role in these dynamic barriers. P-glycoprotein extrudes its substrate drugs on the luminal membrane of the brain capillary endothelial cells into the blood, complicating CNS therapy for some drugs (see Chapter 1). Other transporters in the BBB and the blood-CSF barrier include members of organic anion transporting polypeptide (OATP1A4 and OATP1A5) and organic anion transporter (OAT3) families, which facilitate the uptake of organic compounds such as b-lactam antibiotics, statins, PAH, H2-receptor antagonists, and bile acids on the plasma membrane facing the brain-CSF. Further understanding of influx and efflux transporters in these barriers should translate into more effective delivery of drugs to the CNS while avoiding undesirable CNS side effects and may help to define the...

Pharmacokinetic Interactions that Increase Drug Delivery to the Site of Action

Drug interactions mediated by CYP3A inhibition can be severe (e.g., nephrotoxicity induced by cyclosporine and tacrolimus and rhabdomyolysis resulting from increased levels of statins). Whenever an inhibitor of the CYP3A isoforms is administered, the clinician must be cognizant of the potential for serious interactions with drugs metabolized by CYP3A.

Indirect Indicators Of Irs Activation In Major Depression

Other hallmarks of IRS activation are lower serum total cholesterol, high-density-lipoprotein cholesterol (HDL-C), a lower esterified cholesterol total cholesterol ratio, decreased activity of lecithin cholesterol acyltransferase (LCAT EC 2.3.1.43), and specific changes in polyunsaturated fatty acids (PUFAs). There is now some evidence that alterations in fatty acid metabolism and the composition of phospholipids in serum and membranes are involved in the pathophysiology of major depression (Horrobin, 1990 Smith, 1991 Maes, Delanghe, Meltzer, D'Hondt, & Cosyns, 1994a Maes, Smith, Christophe, Cosyns, Desnyder, & Meltzer, 1996a Maes, Vandoolaeghe, Neels, Demedts, Wauters, & Desnyder, 1997c Hibbeln & Salem, 1995 Maes & Smith, 1998 Peet, Murphy, Shay, & Horrobin, 1998). Some (Morgan, Palinkas, Barrett-Connor, & Wingard, 1993 Glueck, Tieger, Kunkel, Hamer, Tracy, & Speirs, 1994), but not all authors (Swartz, 1990 McCallum, Simons, Simons, & Friedlander, 1994)...

Risk factors for chronic disease The metabolic syndrome MetS

The metabolic syndrome (MetS) is a combination of medical disorders integrated to have a useful description of related cardiovascular risk factors which also predict the risk of developing diabetes. Although there have been arguments against the use of a minimalistic view for these diseases, there is currently a unifying definition for the MetS (Fig. 3.1). According to this (Alberti et al., 2006), obesity and insulin resistance appear to be the causative factors in the development of the MetS. General features include obesity, insulin resistance (correlated with the risk of Type 2 diabetes and CVD), atherogenic dyslipidemia (increased triglycerides and HDL cholesterol), elevated BP, elevated C-reactive protein (CRP proinflammatory state), and a prothrombic state, associated with coagulation and fibrinolytic proteins. Scientific effort has been done to clarify associations between MetS factors, and after decades of effort, some facts can be stated Atherogenic dislipidemia,...

An Overview Of Metabolic Syndrome A Precursor Of Diabetes Heart Disease And Stroke

(6) elevated levels of circulating fatty acids, triglycerides and LDL (4) elevated levels of circulating lipids, especially triglycerides and LDL. Adipose cells function not only as energy storage vessels but also as sources of regulatory molecules. One such regulator is the small protein leptin, which after secretion by fatty tissue travels to the brain where it normally induces a signal to decrease food intake. Another regulator is adiponectin, which increases insulin sensitivity, decreases glucose production in the liver, and increases glucose uptake by the muscle, all of which are antidiabetic activities. Adiponectin also decreases circulatory lipid and cholesterol and is anti-inflammatory. Excess body fat (especially abdominal fat) is associated with deregulation and abnormal function, including diminished adiponectin secretion and increased production of the proinflammatory TNF-a. The dysfunctional behavior of adipocytes in excessively heavy or obese individuals may be a...

Natural Oils And Fats

Naturally occurring oils and fats are comprised of mixtures of various triglycerides (TG) which are more correctly (but rarely) referred to as triacylglycerols, since chemically they are fatty acid tri-esters of glycerol (Fig. 3). Table 4 lists trade names and suppliers of several common natural oils, including some that have been hydrogenated to decrease the number of double bonds, thereby conferring resistance to oxidative degradation (4,13-15,24,25). Naturally occurring triglycerides contain fatty acids of varying chain lengths and degrees of unsaturation (Tables 5 and 6). Based on the hydrocarbon chain

Targeting Multiple Functional and Pathological Deficits

PPARy agonists may thus address the amyloid pathology, neuroinflammatory responses and risk factors (e.g. hypercholesterolemia, obesity, and diabetes) of AD (see Chapter 3). An FDA approved drug on the market for the treatment of diabetes, Avandia, has been shown to provide benefits for AD patients who do not carry the apoE4 gene 139 . A phase III clinical trial is ongoing to test its efficacy in AD patients (Table 1). Five different mechanisms of actions for the treatment of AD are discussed separately in the following chapters. In the opening chapter Drs. Jeffrey Kao and George Grossberg review the use of cholinesterase inhibitors currently on the market as symptomatic treatments for AD. The next four chapters discuss potential disease modifying therapeutic opportunnities that have entered clinical studies. In Chapter 2 Drs. Holly Soares and Larry Sparks review the pleiotropic effects of HMG-CoA reductase inhibitors (statins) that may affect AD pathogenesis. In...

Lipids and fatty acids

Terminus and contain up to six double bonds. Sea lettuces are particularly rich in o3 fatty acids (Ortiz et al., 2006). Eicosapentanoic acid (EPA 20 5) and docosahexanoic acid (DHA 22 6) are the two important fatty acids of sea lettuces, along with the precursor a-linolenic acid (ALA 18 3). Both EPA and DHA are basically derived from ALA through elongation and desaturation (Alamsjah et al., 2008 Ortiz et al., 2006 Ratana-arporn and Chirapart, 2006). The o3 fatty acids have been demonstrated to play significant role in human body. In human body, the beneficial effect of o3 fatty acids can be classified into two main areas. First, these fatty acids sustain normal healthy life through the reduction of blood pressure, plasma triglycerides, and cholesterol, together with increased blood coagulation time. Both EPA and DHA are important for maintenance of normal blood flow as they lower fibrinogen levels and also prevent platelet from sticking each other. Second, they alleviate certain...

Vitamin E In Diabetes

About one-half of the total plasma vitamin E is a constituent of circulating LDL. Interindividual variations in plasma vitamin E are closely related to those in LDL (24,25). The concentration of vitamin E per LDL particle is rather low (i.e., in the order of 5-9 molecules compared with 2200 molecules of cholesterol and 170 molecules of triglycerides) (26). Nevertheless, the level of vitamin E in LDL is an independent factor that influences susceptibility of LDL to oxidation. The lagtime of in vitro LDL oxidation was found to be related to the level of vitamin E in LDL when diabetic patients were supplemented with vitamin E (27,28). For persons with usual nutritional habits, the corresponding relationship was observed in two studies (29,30) but not in others (3,31,32).

Cholesterol And The Phospholipids

Cholesterol and phospholipids find pharmaceutical application as solubilizers, surfactants, and emulsifiers in mixed micelles and emulsions (Fig. 4, Table 11) (28,29). In addition, phospholipids have been used as antioxidants for triglycerides (6) and are the primary constituents of liposomes, which have found only limited application in oral drug delivery due to instability in the GI tract. However, liposomes composed of a 7 2 molar ratio of were found to be stable to pancreatic lipase and bile salts in vitro, suggesting potential application of these formulations in oral drug delivery (30).

Problem With Lipid Standardization Of Vitamin E

There are close correlations between the concentrations of vitamin E and lipids (triglycerides, cholesterol, and phospholipids) in plasma. They are due to the lipophilic properties of vitamin E, and moreover they reflect that the antioxida-tive capacity of lipids is regulated in progression with the lipid mass. -2.9 (cholesterol -5.2) -1.5 (triglycerides -1.3)

Functional diversity of G3 and Gy subunits

Reports on defects of Gp functions leading to genetic diseases are scarce. Polymorphism of the Gp3 gene has been detected with a C825T base substitution in some hypertensive patients, which results in an alternatively spliced Gp3 subunit losing 41 amino acids (Siffert et al. 1998). The deleted region corresponds to one of the seven WD repeats. The shortened Gp3 (named Gp3S) can still fold into a functional protein with six blades only. Gp3S promotes Gi-mediated Ca2+ signals in lymphoblasts and enhances Na+ H+ exchanger activity. Gp3S is subsequently correlated to lower renin and elevated diastolic blood pressure levels, obesity, type II diabetes (Siffert 2000), enhanced chemotaxis of human neutrophils in response to interleukin-8 (Virchow et al. 1999), elevated serum potassium and cholesterol levels (Ishikawa etal. 2000), and coronary artery vasoconstriction (Meirhaeghe etal. 2001).

Steps of ClathrinAP2Mediated Endocytosis

Clathrin-mediated endocytosis can be divided into several distinct steps, including a coat nucleation and assembly phase, maturation of the coated pit, and fission of late coated pits to free vesicles. Finally, coat proteins are shed and disassembled in a process termed uncoating that is mechanistically linked to dynamin-medi-ated scission of the vesicle neck (Newmyer et al. 2003). The clathrin coat is assembled at the cytoplasmic face of the plasma membrane, in part by recruitment of coat proteins from a cytoplasmic reserve, but perhaps also by relocalization of pre-existing clathrin from flat lattices. Recruitment is largely dependent on the AP-2 adaptor complex, which links clathrin to the membrane and coordinates the structural assembly of the coat with the selection of membrane cargo proteins. Many of these display sorting motifs, including tyrosine-based (Yxx0, with 0 being a large hydrophobic amino acid) or acidic-cluster di-leucine motifs that are recognized directly by AP-2....

Lppla2 as a new marker for cardiovascular risk

The association of Lp-PLA2 with risk for CAD has been investigated in a number of different human populations. Data from large Caucasian population studies consistently report a positive association of plasma Lp-PLA2 mass or activity and risk for CAD. The West of Scotland Coronary Prevention Study (WOSCOPS)30 reported that, in men with increased plasma LDL-cholesterol levels (174-232 mg dL), plasma levels of Lp-PLA2 mass were significantly associated with development of CAD events. This association was independent of other traditional risk factors or markers of inflammation including C-reactive protein (CRP). More recently, in a prospective case-cohort study, the Atherosclerosis Risk in Communities study (ARIC), authors reported that circulating levels of Lp-PLA2 mass were associated with incident CAD in apparently healthy middle-aged men and women after adjustment for age, sex, and race.31 Similarly, in the monitoring of trends and determinants in cardiovascular disease study...

Comparison of 18FFDG and 99mTcAnnexin A5 in ApoE mice

Atherosclerotic lesions and for determining lesion vulnerability. Thus, we compared the intralesional distribution of 99mTc-annexin A5 and 18F-FDG in relation to lesion development in ApoE- - mice 10 . ApoE- - mice have been widely used in studies of atherosclerosis, because they spontaneously develop hypercholesterolemia and atherosclerotic lesions similar to those found in humans 11, 12 . These data suggest that ApoE- - mice could be a useful model for the evaluation of tracers for detecting unstable atherosclerotic lesions.

Detection of Increased Metabolism of Inflammatory Cells with 18FFDG

Cholesterol and 18F-FDG accumulation in the simvastatin treatment group. Ogawa et al. 18 treated rabbits exhibiting spontaneous atherosclerosis with an antioxida-tive agent, probucol, and performed 18F-FDG PET before and 1, 3, and 6 months after the initiation of treatment. They found that 18F-FDG accumulation in the arterial wall slowly increased in the control group, but decreased with the reduction of inflammatory reaction in the treatment group, and the accumulation in the arterial wall was undetectable 6 months after the initiation of treatment. These findings indicate the potential of 18FDG PET to evaluate the therapeutic effects of statins and probucol on atherosclerosis, based on the reduction of inflammatory reactions in aortic tissues.

Biological Activity of Fungal 130Glucans

Recently have these antitumour properties been attributable to P-glucans and their derivatives 123 . Schizophyllan (SPG, sizofilan or sizofiran) from S. commune and lentinan from basidiocarps of Lentinus edodes are both approved in Japan for the clinical treatment of several cancers 122 . In addition, there is now well-documented evidence for the effectiveness of P-glucan in treating a range of infectious microbially mediated diseases in humans, and in lowering blood pressure and cholesterol levels in humans 124 .

Supplementation and Drug Interactions

P-Hydroxyl-p-methyl glutarate-CoA reductase inhibitors (statins) in combination with niacin are often the initial therapy prescribed for dyslipidemia to reduce LDL cholesterol and raise high density lipoprotein (HDL) cholesterol. A recent clinical trial examining the efficacy of different lipid-altering and or antioxidant strategies on coronary artery disease indices demonstrated that when statin niacin therapy was combined with antioxidant use (p-carotene, 12.5 mg vitamin C, 500 mg vitamin E, 268 mg) the beneficial response of HDL to the statin niacin therapy was markedly attenuated (P 0.057) (93). Although these results must be verified, they demonstrate the importance of investigating interactive effects of popular drug therapies and high-dose vitamin supplementation.

Coronary Heart Disease

Coronary heart disease (CHD) is a multifactorial disease, for which the main established risk factors are raised serum cholesterol, raised blood pressure and smoking. The proportion of both men and women who are hypertensive steadily increases with age. Compared with men, serum cholesterol levels are lower in women up to the age of 50 years. After the menopause, levels of serum cholesterol in women exceed those of men. In women, therefore, the relative importance of CHD as a cause of death steadily increases with age, whereas in men, its importance declines after 55-64 years of age 181 . CHD accounts for 23 of deaths in women in the UK, and 30 of deaths in men, although rates have been falling since the late 1970s. Rates are low in Far East countries, such as Japan, and also declining 181,182 . Postmenopausal estrogen replacement has been shown to decrease lipoprotein (a) Lp(a) 183, 184 . The synthetic anti-estrogen, tamoxifen, has also been shown to beneficially alter serum lipid and...

Biorelevant Lipids and Surfactants

In the small intestine, the main relevant amphiphiles are bile acids salts, lyso-phospholipids and cholesterol, secreted from the bile, and fatty acids and monoglycerides from lipid digestion. Based on their ability to interact with water, the amphiphiles are characterized as soluble, insoluble swelling, or insoluble non-swelling (Carey and Small, 1970). Bile salts and lyso-phospholipids are characterized as soluble amphiphiles, and they possess an enormous capacity to solubilize insoluble swelling amphiphiles. Only soluble amphiphiles are able to form micelles on their own. Other lipids can be solubilized and transported by these micelle-forming amphiphiles. Phospholipids and monoglycerides belong to the class of insoluble swelling amphiphiles. However, above their phase transition temperature, water can be incorporated between the polar groups, which create a swollen lipid structure. Triglycerides, diglycerides, cholesterol and pro-tonated long-chain fatty acids are insoluble as...

Uptake Distribution and Metabolism of Vitamin E

It should be mentioned that serum levels of vitamin E correlate with cholesterol levels, and hence do not necessarily correlate with vitamin E intake (16). However, except for non- or poorly responding subjects, serum levels of vitamin E can usually be increased up to threefold by intake of dietary supplements reaching a saturation level (20).

Epidemiological Studies of Cholesterol and AD

Initial interest in cholesterol and Alzheimer's disease stemmed from a lengthy historical backdrop. One of the first studies linking cholesterol to AD stemmed from an observation that senile plaques were quite prevalent in the brains of non-demented patients who had died from coronary heart disease 21 , a population known to possess elevated cholesterol levels. Additional studies soon followed demonstrating that the ApoE4 allele of the ApoE cholesterol transporter was a major risk factor for AD 13-16 . Is there a clear association between cholesterol and Alzheimer's disease Although a few studies have observed an association between elevated cholesterol, dementia and AD 22,23 , the majority of cross-sectional studies typically report no association or lower levels of cholesterol in patients with AD compared to controls or VaD patients 24-30 . In two longitudinal population-based studies, higher midlife cholesterol levels were reported to be associated with an increased risk of AD...

Epidemiological Studies of AD and Statin

Although the association between elevated cholesterol and increased risk of AD remains unclear, pharmacologically based epidemiological studies examining statin use have provided informative insights. Statins are a class of drugs known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors 40 . HMG-CoA reductase is the first enzyme in the cholesterol synthesis pathway and inhibition essentially blocks de novo synthesis of cholesterol 40 . As expected, the first HMG-CoA reductase inhibitors were shown to be efficient inhibitors of cholesterol 41,42 . Today, statins are one of the most prescribed medications for lowering blood cholesterol. In 2000, two seminal epidemiological studies were published raising hopes that statins may have some utility in the prevention of dementia presumably through cholesterol lowering mechanisms. These studies utilized a case-control and a nested case-control analysis to examine the relationship between statin use and the prevalence of...

L Protease Inhibitors PIs

Each of the protease inhibitors that have been studied to date has a low incidence of side effects that appear to be class related (Kaul et al., 1999). These rare adverse reactions include hyperlipidemia, lipodystrophy, hemo-lytic anemia, hyperglycemia, and spontaneous bleeding in hemophiliacs. Each reaction has been associated with each of the protease inhibitors. The PI-associated hyperlipidemia is usually an elevation of the triglycerides. In PI-associated lipodystrophy, patients develop aberrant fat deposits around their waists and on the back of their necks (''buffalo humps''). This problem is more cosmetic than medical and may resolve with discontinuation of the PI. PI-associated hyperglycemia can be mild or can present as ketoacidosis with new onset diabetes mellitus.

Influence of the Lipid Dose

The amount of lipid contained in a formulation will influence drug absorption primarily via solubilization in the GIT and potentially, through activation of GI lipid digestion resulting in increased secretion of pancreatic juice and bile. Although the minimum lipid quantity required to activate lipid digestion has not been fully elucidated, oral administration of the poorly soluble antimalarial drug, halo-fantrine, to dogs in a small, pharmaceutically relevant lipid volume 0.3 g of long chain triglycerides (LCT) or mixed long chain mono- and diacylglycerols , triggered the processes of GI lipid digestion and lymphatic drug transport (24). In another study in which conscious, restrained rats received single oral doses of benzo(a)pyrene administered as a solution in 50 or 500 mol olive oil, the lipid volume had no effect on benzo(a)pyrene bioavailability (25).

Roles Of Estrogen In Angiogenesis

Artery diseases in order to maintain blood flow to bypass the blocked coronary artery and protect from heart ischemia and attacks. Uncontrolled and persistent changes in the angiogenic process switch can occur at different stages of tumor progression, depending on tumor type and the surrounding environment.103 Physiological and pathophysiological angiogenesis can be regulated by various positive and negative regulators, including vascular endothelial growth factor (VEGF), fibroblast growth factors (FGFs), platelet-derived growth factors (PDGFs), epidermal growth factors (EGFs), thrombospondin-1 (TSP-1) and various types of statins, and inhibitors of HMG-Co and A-reductase.103 Although, the molecular mechanisms associated with physiological and pathophysiological angiogenesis have not been fully elucidated, it is assumed that angiogenesis is the result of imbalanced expression and function of positive and negative regulators.103105 The angiogenic switch induced by imbalanced functions...

Natural Products as Lead Compounds for Drug Discovery

Another excellent example of commercial drugs developed from natural products includes a class of compounds known as the statins. These molecules represent a remarkable class of cholesterol lowering agents which act as enzyme inhibitors 1 . The statins have been exploited extensively by the pharmaceutical industry as they reduce the risk of heart attacks and strokes 6, 7 . Mevastatin, Fig. 1.2, was the first molecule to be isolated from this class of compound and it became known as a Type I statin. Its isolation from Penicillium citrinum in 1970 sparked widespread interest as it was found to be an effective and potent statin 1 . However, largely due to problems in preclinical trials, Mevastatin never reached market. Nevertheless, it can be regarded as a landmark for drug discovery as it has paved the way for synthetic Type II statins. Atorvastatin, Fig. 1.3, a Type II synthetic statin, is currently marketed as Lipitor and holds the position as the best selling drug worldwide....

Endocrine Active Compounds Interactions and Adverse Endpoints

Endocrine active compounds (EACs), or sometimes called endocrine disrupting chemicals, are a wide class of compounds defined by the EPA as Exogenous agents that interfere with the production, release, transport, metabolism, binding action or elimination of natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes. Despite the negative title, endocrine disrupting agents with an anti-estrogenic action can be used in clinical applications, especially for fertility control or treatment of certain hormone-dependent cancers. The main anti-estrogen being used to date is tamoxifen. This non-steroidal EAC has turned out to be effective in the treatment of breast cancer because of its partial agonist effect in decreasing the action of estrogen in breast tissue 26 . It also has several beneficial side effects like maintaining bone-density and reducing blood cholesterol levels. However, while tamoxifen works as an antagonist in...

Recent Studies Of Ketogenic Diet Efficacy

Although various other medications became available in the ensuing years, clinical researchers continued to publish KD efficacy results (8-11). Livingston (9) reported that 54 of his patients on the classic KD achieved complete seizure control, and an additional 26 achieved partial control. The Sills study (10) featured a modification of the classic KD by substituting medium-chain triglycerides (MCTs) in an emulsion form for better palatability. MCTs served as the primary source of calories from fat, after the changes proposed by Huttenlocher (8), and this diet was a viable alternative method of achieving ketonemia. Forty-four children of 50 who started on the Sills diet tolerated it, with the following results 8 achieved complete, i.e., 100 , control and half were able to stop all anticonvulsants 4 had excellent (> 90 ) control 10 had

SHydroxycholesterol Cerebrosterol

Previously, a prospective placebo-controlled, randomized intent-to-treat study had been run to test atorvastatin for benefit in the treatment of mildmoderate AD patients. Preliminary results from the Alzheimer's disease cholesterol lowering trial (ADCLT) has been described in detail 73 . In brief, 67 AD subjects were randomized to either 80 mg atorvastatin or placebo and treated for one year. Blood for biomarker analysis was collected at baseline, 3, 6, 9 and 12 months post-dosing. To determine whether atorvastatin might impact brain cholesterol, a subset of samples was analyzed by GCMS for changes in 24S-hydroxycholesterol (also known as cerebrosterol). Statistical analysis utilizing a repeated measures approached identified no statistical differences in 24S-hydroxycholesterol concentration over time between atorvastatin and placebo treated groups. However, 24S-hydroxycholesterol levels were slightly increased at 9 and 12 months in the placebo group and were unchanged at the same...

In Vitro Characterization of Seddssmedds

Pouton (4) classified lipid-based formulations into three categories based on the polarity of the excipient blends (Table 2). Due to their relative simplicity Type I formulations, which are simple solutions of the drug in triglycerides and or mixed glycerides, are a reasonable starting point in the search for a lipid-based formulation. Type II formulations that add a lipophilic surfactant (HLB < 12), are employed when Composition ( ) Triglycerides or

Mechanisms of Absorption

That interact strongly with albumin might show enhanced uptake from the interstitial space through mechanisms that drive albumin reuptake from the interstitial space. Thus, absorption characteristics of an injected protein or peptide can be altered on the basis of its interactions with albumin (104). Also, a lipid-modified protein or peptide that specifically interacts with the fatty acid-binding sites of serum albumins or the lipid phospholipids transport protein a-1 lipoprotein might have enhanced uptake (105). Similarly, b-lipoprotein is capable of transferring cholesterol and triglycerides proteins or peptides associated with such materials could have altered uptake characteristics from an SC injection site (106), and proteins or peptide therapeutics that contain or are associated with the fraction-crystallizable (Fc) domain of an antibody provide another strategy to alter PK, PD, and metabolic events at an SC injection site (107,108).

Preparation and effect of HfPS1 in SD rats

The abuse of ethanol is associated with detrimental effects on several bodily organs and is one of several factors causing gastrointestinal disorders. For the treatment of gastrointestinal symptoms such as ulcerative hemorrhages and perforations, many pharmaceutical products (e.g., non-steroidal anti-inflammatory drugs, NSAIDs) have been developed (Higham et al., 2002). However, NSAID group presents many important medical problems relating to their expense and side effects, despite recent pharmaceutical advances that have generally improved their therapeutic effects. Therefore, many researchers are investigating the natural materials that have pharmaceutical effects with fewer side effects. Among these natural materials, seaweed compounds, many of which are polysacchar-ides, have been studied for their various pharmaceutical effects and diverse biological activities. Sulfated galactans from the red marine alga Champia feldmannii show acute anti-inflammation, anticoagulation, and...

Ketogenic Diet In Adults

Both partial and generalized seizures responded favorably. All patients noted constipation and bloating, and women reported menstrual irregularities. Cognitive improvement was observed, similar to what has been reported in children. Seven patients noted improved cognition and mood, whereas 2 patients reported worsened concentration. Cholesterol and triglyceride levels increased, with an increased ratio of cholesterol to high-density lipoprotein (HDL). One patient with long-standing high cholesterol discontinued the diet after 5 mo and 5 mo later experienced a myocardial infarction. Although it is doubtful that the KD was responsible for this adverse event, it must be asked whether the diet contributed to this cardiovascular morbidity. The high fat content of the diet and the paucity of healthy foods such as vegetables and fruit raised concerns regarding the potential metabolic consequences of the KD. Cholesterol levels tended to rise over time in patients on the diet (mean pre-diet...

Cautions And Potential Complications

A recent study in children (15) found that the KD was associated with increases in serum lipids. This included elevations in serum low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglycerides, apolipoprotein B, and apolipoprotein A-1 levels. HDL cholesterol was modestly reduced, so the mean cholesterol HDL ratio changed from 3.36 at baseline to 5.20, a significant increase. These alterations in serum lipids persisted for 24 mo, the duration of therapy. These findings raise

Influence of Lipid Components on Lymphatic Transport

The mesenteric lymphatic transport of halofantrine, administered in SMEDDS containing either MCT or LCT as the lipid component, has been studied in conscious dogs (24). The fraction of the administered dose of halofantrine transported in the lymph after administration of the LC-SMEDDS was 28.3 compared with only 5.0 after administration of the MC-SMEDDS. The marginal lymphatic transport of halofantrine associated with the MC-SMEDDS formulation is explained by its content of mono- and diglycerides of MCTs, which unlike long chain fatty acid (LCFA), are not lymphotropic. The foregoing study was repeated by Holm et al. (50) using SMEDDS formulations in which the MCT and LCT lipid components were replaced with structured triglycerides medium long medium chain fatty acid (MLM) C8.0-C18.2-C8.0 and long medium long chain fatty acid (LML) C182-C80-C182 , respectively . Structured triglycerides are prepared by selectively esterifying medium and long chain fatty acids to specific positions on...

Secondary Stroke Prevention

Include the identification and modification of risk factors. In most instances, data on the potential benefits of risk-factor management for secondary stroke prevention have been extrapolated from studies focused on primary prevention. In the last few years, however, a body of evidence has shown that antihypertensive therapy decreases recurrences by one-third among subjects who have already suffered a first stroke.99-101 Cigarette smoking increases the risk of stroke 1.5-fold and should be intensely discouraged.102 Although specific evidence regarding the benefits of secondary stroke prevention is still lacking, it has been suggested that statins may reduce the incidence of first stroke by 30 in patients with symptomatic coronary artery disease or hypercholesterolaemia, and a similar efficacy might be expected to occur in patients with prior stroke.103 Nevertheless, there is still a large gap between the benefits of risk-factor control in reducing recurrences as reported by several...

Oxidized Lipid and Atherosclerosis

Comparison of atherogenicity of crystalline and amorpous cholesterol showed the latter to be less cholesterolaemic but more atherogenic. The broad melting point of amorphous cholesterol suggests the presence of impurities (Kritchevsky et al., 1969). The angiotoxicity and atherogenicity of cholesterol oxides has been reviewed by Peng et al. (1991). Hodis et al. (1991) reported that normal rabbit plasma contains 81 mol l-1 of cholesterol oxides. After feeding a high cholesterol diet to rabbits for 6 weeks the level of plasma cholesterol oxides rose by a factor of 5, while total plasma cholesterol rose by a factor of 64. Aortic levels of total cholesterol oxides rose 150 . Several compounds that had not been present in arteries of the control group were isolated from arteries of cholesterol-fed rabbits, namely, cholesterol p-oxide, 7-ketocholesterol and 25-hydroxy-cholesterol. There have been earlier reports of isolation of 26-hydroxy-cholesterol (Smith and vanLier, 1970) and polar...

Question And Answer Session

PHILIPPART I have one comment on the triglycerides. Many years ago, I did an experiment by exposing cultured fibroblasts to various lipids, including triglycerides. You get very good uptake, but EM on these cells shows it's mostly in the form of droplets. So we get it in, and then probably it remains quite inert. So that may not be the whole story.

Biologic Activity of the Tocotrienols Importance of Metabolism

No differences were observed in plasma cholesterol levels, LDL cholesterol levels, or LDL apolipoprotein B concentrations, suggesting that the tocotrienols were ineffective in modulating cholesterol synthesis. Importantly, tocotrienyl supplements did not affect plasma a- or y-tocopherol concentrations. Twelve hours after the last dose of supplemental tocotrienyl acetates, fasting plasma concentrations of a-, y-, and S-tocotrienols were 1, 0.5, and 0.1 mol L, respectively. Apparently, tocotrienyl acetate supplements are hydrolyzed and absorbed, but plasma tocotrienol concentrations remain barely detectable. The reason for these relatively low concentrations compared with the 20 mol L a-tocopherol concentration is the very fast clearance of the plasma tocotrienols, as demonstrated by Yap et al. (29).

Antagonizing MicroRNAs for Therapeutics

The changes in liver-gene expression were normalized to control levels coinciding with normalized miR-122 and plasma cholesterol levels. Previously, cholesterol conjugated 2'-O-Me AS ONs (antago-mirs) have been used to silence miRNAs, including miR-122.143 In a similar study, unconjugated 2'-MOE AS ONs were used to inhibit miR-122 in both normal and diet-induced obese mice.144 Both studies reported a low plasma cholesterol loss-of-function phenotype.143,144 Antagonism of miR-122 by LNA-antimiR confirmed this phenotype, resulting in reduction of plasma cholesterol by 40 .142 The decrease in plasma cholesterol levels was maximal one week post-treatment and then returned slowly to baseline. Thus, the observed changes in gene expression appear to precede reduction in cholesterol, which, in turn, appears longer lasting than changes in miR-122 target gene expression. This suggests that coordinated changes in miR-122-associated gene networks are responsible for the control of cholesterol and...

Restricted Ovulatory Hens

Restricted Ovulator (RO) hens carry a genetic defect which results in the cessation of egg laying when these hens were exposed to a prolonged photoperiod (Smith and Kummerow, 1989). Such hens developed an extreme hyperlipidaemia compared with laying hens. The plasma cholesterol concentration increased to 1380 compared with 118 mg dl-1 for laying hens (Table 14.1). The triglycerides concentration increased to 8160 mg dl-1 and the oxidized lipids, as measured by thiobarbituric acid reaction (TBAR) concentration, increased to 40.9 mol ml-1. When the diet of RO hens was supplemented with vitamin E (1000 IU kg-1), the plasma level of triglycerides and cholesterol did not decrease significantly, but the TBAR level and the intimal thickness of the coronary arteries did decrease by 79 and 37 , respectively. Therefore, hyperlipidaemia without lipid peroxidation either did not promote atherogenesis or did so at a much reduced rate. Triglycerides (mg dl 1)

Adverse Effects During Maintenance Of The Ketogenic Diet

2-4 ), gastrointestinal symptoms (vomiting, constipation, diarrhea, abdominal pain) (12-50 ) irritability, lethargy (4-9 ), and refusal to eat (2,7-12). Carnitine deficiency has also been demonstrated in some children on the KD (13-15). Hypercholesterolemia has been reported in 29-59 of children on the KD (10-12). Theda et al. (16) found an elevation of very-long-chain fatty acids in 13 of 22 plasma samples from KD patients.

Lipids and Biological Membranes

Triglycerides are the chemical form in which most fat exists in food as well as in the body. A triglyceride is made up of a three-carbon molecule called glycerol, which is bonded to three fatty acids. Fatty acids contain long chains of 12 to 24 carbon atoms. The carbons in fatty acids are bonded to varying numbers of hydrogen atoms. Liquid triglycerides are called oils and are found chiefly in plants, although triglycerides from fish are also mostly oils. Triglycerides that are solid or semisolid at room temperature are called fats, and they are mostly found in animals. There are two kinds of fats saturated and unsaturated. Unsaturated fats have at least one double bond between the carbons of the fatty acids. In a double bond, two pairs of electrons are shared by two atoms. This makes double bonds much stronger than single bonds. Saturated fats have no double bonds and have more hydrogens than unsaturated fats. Fats have differing properties depending on whether their fatty acids are...

Longchain Polyunsaturated Fatty Acids Their Role In A Ketogenic Diet

Thus, at first glance, the possibility that KDs exert their anti-convulsant effects via an LC-PUFA-based mechanism seems unlikely. Interestingly, however, an elevation in LC-PUFAs has been reported in subjects fed a KD. Anderson et al. (39) reported significantly elevated serum levels of ALA, docosapentaenoic acid (DPA, 22 5rn6), docosapentaenoic acid (DPA, 22 5rn3), and docosatetraenoic acid (DTA, 22 4rn6) in rats fed a KD. More recently, Fraser et al. (25) documented a significant increase in LA, AA, and DHA in serum free fatty acids, triglycerides, and phospholipids in nine pediatric patients on a KD for treatment of refractory seizures. Seizure reduction in these patients was positively and significantly correlated with serum total AA (r2 0.53, p < 0.05), and a similar relationship between seizure reduction and serum total DHA approached significance (r2 0.41, p 0.09). Taken together, these two studies indicate that the high-fat KD elevates serum LC-PUFA...

Antiobesity effects of seaweeds

The parauterus adipose tissue weight, and hepatic TG, serum TG, and TC levels in the HFD-TK group were significantly less than those in the HFD-NSK group. The fecal TG and TC levels in the HFD-TK group were significantly higher than those in the HFD group, and fecal TG in the HFD-TK-group was significantly higher than that in the HFD-NSK group. Consequently, it was demonstrated that TK consumption reduced the accumulation of visceral fat caused by HFD, and this effect of TK was more powerful than that of NSK, due to TG and cholesterol excretion in the feces. This report concluded that alginate may be one of the active components in Laminaria sp. In previous reports, alginate has been reported to have hypoglycemic and cholesterol-lowering effects by acting as a viscous soluble dietary fiber (Kimura et al., 1996 Pasquier et al., 1996 Paxman et al., 2008).

CoQ10 and lipoproteins

In one experimental study, Singh et al. (1997) demonstrated that lovastatin has a modest antioxidant activity. However, statin drugs lead to a reduction in CoQ10 status due to their inhibition of endogenous CoQ10 synthesis. This indicates that treatment of hypercholesterolaemia with these drugs should be combined with CoQ10 to prevent its depletion.

Solubilizing Excipients and Mixtures

There is a wide selection of solubilizing excipients that can be generally categorized into various types including water-soluble organic solvent excipients, water-insoluble organic solvents excipients, triglycerides, semi-solids, surfactants, phospholipids, and cyclodextrins (Table 3). The question as to which solubilizing vehicle to choose for a particular drug molecule depends on many factors, but in general the formulation philosophy and approach is from simple to complex, meaning to minimize the formulation components. The reasons to minimize the excipients include overall simplicity, cost of goods, ease of procurement, ease ofmanufacture, and very importantly to minimize toxicity. Table 4 is a flow chart of a suggested order of solubilization approaches for oral formulations arranged in a simple to more complex manner. Tables 5 and 6 are listings of solubilizing vehicles used in oral formulation filled into capsules and in oral solutions, respectively. The salt form of the drug...

Highdensity Lipoproteins

Mature HDL can be separated by ultracentrifugation into HDL2, which are larger, more cholesterol-rich lipoproteins, and HDL3 which are smaller and denser. Newly formed HDL3par-ticles are converted to HDL2 by accepting more free cholesterol, which is then esterified by lecithin cholesterol acyltransferase (LCAT). As the cholesteryl ester content of the HDL2 increases, the cholesteryl esters of these particles begin to be exchanged for triglycerides derived from any of the triglyceride-containing lipoproteins (chylomicrons, VLDL, remnant lipoproteins, and LDL). This exchange is mediated by the cholesteryl ester transfer protein (CETP), which in humans accounts for the removal of about two-thirds of the cholesterol associated with HDL. The transferred cholesterol subsequently is metabolized as part of the lipoprotein into which it was transferred. The triglyceride transferred into HDL2 is hydrolyzed in the liver by HL, regenerating smaller, spherical HDL3 particles that recirculate and...

Hyperlipidemia And Atherosclerosis

The major conventional risk factors for CHD are elevated LDL-C, reduced HDL-C, cigarette smoking, hypertension, type 2 diabetes mellitus, advancing age, and a family history of premature (men < 55 years women < 65 years) CHD events in a first-degree relative. Control of the modifiable risk factors, which account for 85 of excess risk, is especially important in preventing premature CHD. When total cholesterol levels are < 160 mg dL, CHD risk is markedly attenuated, even in the presence of additional risk factors. This pivotal role of hypercholesterolemia in athero-genesis gave rise to the almost universally accepted cholesterol-diet-CHD hypothesis elevated plasma cholesterol levels cause CHD diets rich in saturated fat and cholesterol raise cholesterol levels and lowering cholesterol levels reduces CHD risk. Clinical trials with effective cholesterol-lowering drugs, the statins, have documented the safety and efficacy of cholesterol-lowering therapy in preventing CHD. Patients...

Adverse Effects And Drug Interactions

The resins are generally safe, as they are not systemically absorbed. Since they are administered as chloride salts, rare instances of hyperchloremic acidosis have occurred. Since they increase triglyceride levels, severe hypertriglyceridemia is a contraindication to the use of cholestyramine and colestipol. At present, there are insufficient data on the effect of colesevelam on triglyceride levels. Cholestyramine and colestipol both are available as a powder that must be mixed with water and drunk as a slurry. The gritty sensation is unpleasant to patients initially but can be tolerated. Colestipol is available in a tablet that reduces the complaint of grittiness but not the GI symptoms. Colesevelam is available as a hard capsule that absorbs water and creates a soft, gelatinous material that allegedly minimizes the potential for GI irritation. Patients taking cholestyramine and colestipol complain of bloating and dyspepsia, which can be substantially reduced if the drug is...

HPLC Analysis of Plasma a and yTocopherol

The plasma concentration of a- and y-tocopherol were measured by high-performance liquid chromatography (HPLC) as described previously (33). Briefly, an internal standard of a-tocopherol acetate (Sigma, Dorset, UK) was added to 200 L of plasma and vortexed. This was then mixed with cold hexane (500 L) and vortexed again. The hexane layer was removed and evaporated to dryness under nitrogen. The dry extract was resuspended in methanol (400 L) for analysis on a Gilson HPLC system (Anachem, Beds, UK) using reverse-phase HPLC. The extracted sample (100 L) was then injected onto an Apex II Octadecyl 5- .m 10-cm column preceded by an Apex Bio300 Guard column 4.6-mm i.d. cartridge (Jones Chromatography, Glamorgan, UK). The separation was achieved using a mobile phase of 98 methanol 2 water set at a flow rate of 1 mL min. The a-tocopherol, y-tocopherol, and tocopherol acetate were measured using ultraviolet light detection at 292 nm. External standards of a-tocopherol (Sigma) and y-tocopherol...

Dietary intervention trials and secondary prevention

Clinical trials using dietary intervention with clinical endpoints are, up to the present, from secondary prevention. In a study using an a-linolenic acid-rich diet patients were randomly assigned after first MI to the experimental (n 302) or control group (n 303) (de Lorgeril et al., 1994 Renaud et al., 1995). Subjects in the experimental group were advised to eat more bread, more vegetables and legumes, more fish, less meat (beef, lamb and pork), it being replaced by poultry, to have no day without fruit, and to replace butter and cream with a margarine comparable with olive oil. The experimental group consumed considerably less lipids, saturated fat, cholesterol and linoleic acid, but more oleic acid and a-linolenic acid and had increased plasma concentrations of these nutrients and also of vitamins C and E. The diet was also rich in folic acid. After follow-up of 27 months those in the experimental group had a relative risk of 0.27 (95 CI 0.12-0.59, P 0.001) of MI or cardiac death...

Discovery of Tyrosine Based Sorting Signals

The cloning of several genes encoding endocytic receptors in the early 1980s failed to reveal the presence of conserved sequences that could correspond to the hypothetical endocytic signals. This perplexing finding began to be explained with the discovery by the group of Brown & Goldstein that substitution of a cysteine codon for a tyrosine codon in the cytosolic domain of the LDL receptor, detected in a patient with familial hypercholesterolemia, abrogated the rapid internalization of the receptor (17). Later studies demonstrated that the critical tyrosine residue was part of the sequence motif NPXY (18), found not only in the LDL receptor but also in other cell surface proteins such as the LDL receptor-related protein 1 (LRP1), megalin, the 3 subunits of integrins, and the -amyloid precursor protein (Table 3). Many other receptors known at the time, such as the transferrin receptor, the asialoglycoprotein receptor, and the cation-dependent and cation-independent mannose...

Effects of Fruit and Vegetables Biochemical Observations

By contrast, Singh et al. (1992b) found over a 12-week period that fruit and vegetable administration in subjects at high risk of CHD lowered totaland LDL-cholesterol and triglyceride levels, and increased HDL-cholesterol (see Chapter 16). Another study by Wise et al. (1996) using dehydrated fruit and vegetable extracts over a period of 28 days in 15 healthy adults aged 18-53 years produced increases of the order of 50- to 2000-fold in carotenoid and tocopherol levels, while serum lipid peroxides decreased fourfold during the intervention period, with much of this lowering taking place during the first week.

Therapeutic Implications

Cholesterol as well as triglycerides through the use of HMG-CoA reductase inhibitors, better known as statins. However, it has been noted that statins likely have vasoprotective properties outside of control of serum lipids and have immunomodulating effects that also lead to regression prevention of atherosclerotic disease. Statins inhibit HMG-CoA reductase preventing the synthesis of cholesterol from mevalonic acid, and this has long been believed to be the main mechanism of cardioprotection. There are now data suggesting that statins also have anti-inflammatory effects that include inhibition of leukocyte recruitment and adhesion (143-147), reduction in chemokine production, upregulation of peroxisome proliferator-activated receptor (PPAR)-a and -y (144-149), down-regulation of MMPs with concomitant upregulation of TIMP-1 (145,146), subversion of Th response toward a Th2 response through inhibition of proin-flammatory cytokine production (e.g., TNF-a and IL-1P) (144-147), and...

Bioavailability Enhancement by Means of Physicochemical Mechanisms

As a consequence of the intestinal processing that lipids undergo before absorption, there has been significant interest in assessing the ''digestibility'' of formulation lipids as a potential indicator of in vivo bioavailability enhancement. In this regard, digestible lipids such as dietary fats (triglycerides, diglycerides, fatty acids, phospholipids, cholesterol, etc) are generally more effective in terms of bioavailability enhancement than indigestible oils such as mineral oil 2931 . However, more complex correlations of lipid chain length (medium chain versus long chain lipids) or lipid class (triglycerides versus diglycerides or mono-glycerides) with digestibility and bioavailability enhancement have met with little success. Perhaps the most well-known example of the bioavailability-enhancing effects of microemulsion formulations is that of cyclosporin. Cyclosporin (CY) is a cyclic undecapeptide with potent immunosuppressive activity, which is lipophilic (log P 2.92) and poorly...

Extraarticular Disease Manifestations

Cardiovascular (CV) morbidity and mortality in RA occur at rates greater than would be expected from the profile of established CV risk factors. Diabetes mellitus, hypercholesterolemia, hypertension, cigarette smoking, and obesity are generally powerful classifiers of CV risk and when comparing the profiles of these risk factors in people with and without RA, they are similar. Thus, there must be RA-specific factors explaining the increased risk. Dividing the patients in younger and older patients demonstrates that such factors are more common in the younger age group. In older patients, the

Concluding Remarks

The information reviewed in this article illustrates how far we have come in the understanding of the molecular mechanisms of signal-mediated protein trafficking to endosomes and lysosomes. Many issues remain unresolved, but with the powerful tools now available we can expect these to be elucidated in the not too distant future. Among the outstanding questions are the identification of the complete repertoire of sorting signals and their binding partners, the explanation of the structural bases for the recognition of all signals, the demonstration of the exact sorting events mediated by particular signals and recognition proteins, the detailed molecular description of complex pathways of signal addition and detection (as is the case for ubiquitin), the regulation of signal recognition, and the contribution of luminal extracellular and transmembrane domains to sorting. The current knowledge of the mechanisms of signal-mediated protein sorting has already contributed to the elucidation...

Arterial Imaging Studies

Using data from the Cholesterol Lowering Atherosclerosis Study (CLAS) (14), less carotid IMT progression was found for high supplementary vitamin E users compared with low vitamin E users (15). However, in the Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), no vitamin E-induced differences in atherosclerosis progression (16) were observed. The majority of these studies indicate that vitamin E protects against carotid thickening.

Controlled Intervention Trials

The ATBC trial (24) indicated that in heavy smokers, vitamin E produced a 32 lower risk of prostate cancer and a 41 lower mortality from prostate cancer (25). SPACE, Secondary Prevention with Antioxidants of Cardiovascular Disease in Endstage Renal Disease (26), showed a 46 reduction in myocardial infarction, ischemic stroke, peripheral vascular disease, and unstable angina. The HPS Medical Research Council (MRC) British Heart Foundation (BHF) Heart Protection Study demonstrated that statins can reduce the risk of heart attack or stroke by up to one third, but vitamin C and or Vitamin E were without benefit (Congress of the American Heart Association Scientific Sessions, 2001, November 11-14, Anaheim, California).

Water Soluble Solubilizing Vehicles in Capsules Two Solubilizing Excipients

A mixture of PEG 400 and propylene glycol is commonly used in over-the-counter soft gelatin capsules, as is a mixture of PEG 400 and medium-chain triglycerides. Some prescription products contain a mixture of peppermint oil and PEG 400. 2) A mixture of PEG 400 and medium-chain triglycerides solu-bilizes 200 mg of ibuprofen and 30 mg of pseudoephedrine in over-the-counter liquid Advil Cold & Sinus liquid gel-caps.

Reduction of plasma lipid levels

One proposed mechanism by which tea may protect from CVD is via its effects on lipid and lipoprotein levels, and a number of epidemio-logical studies have studied the relationship between tea consumption and a possible cholesterol-lowering potential.15 A further inverse relationship between green tea consumption and serum cholesterol and triglyceride levels has been identified in another epidemiological study, also conducted in Japan. While ingestion of ten cups of green tea per day (estimated to contain 360-540 mg of epigallo-catechin gallate) did not lower total plasma cholesterol levels of post-menopausal women, male subjects were found to have decreased serum levels of both total cholesterol and triglycerides.17 One study was conducted to determine the effects of black tea consumption on the blood lipid profiles of a group of mildly hyper-cholesterolaemic adults, and showed significant reduction in cholesterol levels. Ingestion of five servings of black tea per day during the...

Vitamin E As An Antioxidant

Frontiers in atherosclerosis research are thus moving from lipoprotein metabolism and control of hyperlipidemia to the cellular events in the artery wall. Emerging hypotheses, including the oxidative modification hypothesis of LDL, suggest a new approach, with antioxidants, that could complement and be additive to the control of hypercholesterolemia in the prevention of atherosclerosis (Steinberg and Witztum, 1990).

Consumption Of Vitamin E And The Development Of Atherosclerotic Modifications Of The Arterial Wall

Although the amount of plaque formation in the aorta of WHHL rabbits (undergoing spontaneous atherosclerosis) did not differ significantly in vitamin E-supplemented and nonsupplemented animals, the concentration of cholesterol in lesions of the aortic arch was approximately 25 lower in vitamin E-supplemented animals. Plasma levels of total cholesterol, LDL cholesterol, and triglycerides were 20-30 lower in the vitamin E-supple-mented group compared to the control group. Blood and aortic tissue levels of lipid peroxides decreased in vitamin E-supplemented rabbits on high cholesterol diets or on regular rabbit chow. Atherosclerotic plaques were significantly smaller in cholesterol-fed rabbits on vitamin E supplementation than in nonsupplemented rabbits (Prasad and Kalra, 1993).

Commentary to Intervention Studies

The lack of a consistent association among serum selenium, vitamin A or vitamin E levels, and risk of death from coronary heart disease was reported in only epidemiological studies in Finland and the Netherlands (Kok et al., 1987 Salonen et al., 1985). However, it was also noted that these data must be considered with reservation due to several methodological problems, including lack of standardization for cholesterol and triglycerides (Gey et al., 1991).

Direct Capsule Filling Technique

Dispersions into hard gelatin capsules was not described until 1987 (102). Since melting an excipient can alter its crystallinity by converting to metastable crystalline or amorphous states, Hawley et al. (103) evaluated the effects of melting and subsequent congealing on the rheology and crystalline structure of various poloxamers, polyethelene glycols, myristic acid, triglycerides, and selected block copolymers of polyethylene oxide polypropylene oxide. It was observed that these manufacturing unit operations did not substantially change the crystalline structure of the studied excipients. For a successful scale-up, excipients selected for direct filling operations and the drugs dissolved in the molten formulation should remain physically and chemically stable for the duration of the capsule filling operation. In addition, the viscosity of the molten fill can not change and must be within a range that allows accurate filling by the liquid handling apparatus. In one study, Robinson...

New Chemical Entities

When a potential therapeutic approach is investigated, molecules will be synthesised which are considered likely to have the required activity. For example if one wanted to suppress an enzyme involved in a harmful biological process, then if one understands the structure, 3-D shape and actions of the enzyme, it may be possible to design chemicals that will inhibit this activity. The discovery that high levels of cholesterol were associated with premature death from coronary heart disease was soon followed by the discovery that the enzyme HMG CoA reductase was the rate limiting enzyme in the endogenous synthesis of cholesterol. Several pharmaceutical companies then invested many millions of dollars looking for agents that would inhibit this enzyme. Through intelligent screening of many molecules, it was discovered that molecules of a particular class had the desired activity. These molecules would be further divided to find those with most activity. This class of compounds are now...

Vitamin E Supplementation and CVD Risk Factors in Diabetes

We have recently carried out the first trial on type I diabetic patients. We examined the effects of daily supplementation with vitamin E on blood GHb, glucose, TG and cholesterol levels. Since blood GHb can be affected by the red cell count, we also determined the effect of vitamin E on red cell indices, not previously examined in any of the clinical trials with diabetic patients. In a randomized double-blind study 35 diabetic patients visiting the clinic were assigned to a modest dose of oral vitamin E 100 IU day-1 or placebo capsule daily for 3 months. There was no control on the diet of these patients.

Brain Metabolism Of The Ketone Bodies Relationship To Glutamate Metabolism

Although glucose ordinarily is the sole fuel of the brain, when the plasma concentration of the ketone bodies rises into the range of 2-4mM, these organic acids can satisfy as much as 70 of the metabolic requirements of the brain (26). Such intense ketone-mia occurs most commonly during starvation, when hepatic glycogen stores become depleted and the breakdown of triglycerides in adipose tissue favors the delivery of fatty acids to the liver. The liver first oxidizes these lipids to acetyl-coenzyme A (acetyl-CoA), and from this intermediate the liver synthesizes the major ketone bodies 3-hydroxybutyrate and acetoacetate. Liver does not utilize ketone bodies to satisfy its own metabolic needs. This requirement is met primarily by the large influx of fatty acids from adipose tissue. Instead, the liver releases the ketone bodies into the bloodstream, where they are taken up by a number of tissues, primarily skeletal muscle, kidney, and the brain.

Active Transports and Efflux

Cell-based models represent the next level of sophistication of permeability assays as they address both the physical and the biochemical barrier aspects. The most commonly used systems are the Caco-2 and P-glycoprotein transfected MDCK monolayer models. While the importance oftransporters in GI tract absorption is probably not major (unless a low dose is considered) there is growing evidence of their importance in drug elimination and distributionproperties. The impact of P-glycoprotein onbrain exposure is well documented in the literature. Perhaps less well known is the organ-specific distribution induced by transporters in some cases this transporter-driven organ-specific accumulation of drug is beneficial as in the case of statins 22 while in other cases it can lead to deleterious effects such as the renal accumulation of beta lactams in tubular cells 23 , both mediated by organic anion transporter uptake.

Effects of soy consumption on plasma lipids

Content soy protein significantly decreased total and LDL-C levels in subjects with the highest baseline LDL-C concentrations.31 A study of premenopausal women found that subjects taking high isoflavone soy protein had lower LDL-C concentrations and lower ratios of total to HDL-C and of LDL-C to HDL-C than those women taking the low isoflavone soy protein.31 These studies support the view that the iso-flavone content of soy protein is responsible for the cholesterol-lowering capacity of soy products.28 In postmenopausal women oestrogen replacement therapy causes a decrease in their plasma cholesterol concentrations.32 Consequently, the oestrogenic activity of isoflavones, particularly genistein and daidzein, has been hypothesised to cause a reduction of cholesterol levels observed in mild hypercholesterolaemia.32 A number of mechanisms implicated in the cholesterol-lowering activity of the isoflavones include altered thyroid status, enhanced bile acid excretion, leading to reduced...

Abcr Is A Member Of The Atp Binding Cassette Abc Transporter Family

Human genetic studies have demonstrated that the different classes (A to G) of ABC transporter genes correlate with a variety of inherited diseases, all of which are commonly characterized by defects in the transport of specific substances. Cases in point, in addition to ABCA4, include the ABCG gene associated with accumulation of dietary cholesterol in sitosterolemia (54-63), the cystic fibrosis transmembrane conductance regulator gene (CFTR) (64-71) and the P-glycoprotein multidrug resistance gene, which

Plantprovided polyunsaturated fatty acids

It is clear that there are benefits derived from substituting n-6 PUFAs for saturated fats, which leads to a reduction in cardiovascular deaths, via reduction in cholesterol levels. It is not known whether the benefits associated with consumption of ALA are independent, or are related to its biotransformation to EPA and DHA.

Cyclodextrins and Lipidbased Systems

Emulsions are thermodynamically unstable liquid liquid dispersed systems that cause phase separation. Although natural CD do not possess any surface-active properties, they are able to stabilise simple oil-water 127-130 and multiple oil-water-oil emulsions 131-133 . At the oil water interface, a partial inclusion is formed between the main components of the vegetable oils (triglycerides) and CD. Only one fatty acid chain of the triglyceride can be entrapped with two or three CD molecules depending on the length of the hydrocarbon chain. The two other fatty acid chains are not included in the CD. Due to its amphiphilic property (a hydrophilic head and a hydrophobic tail), the partial inclusion complex could play the role of a surface-active agent 134 . The best emulsifying effect is observed with a- and P-CD whereas the y-CD is too wide to lead to an optimal interaction with the fatty acid chains 127, 133 . Active ingredients may be added to emulsions formulated with CD and vegetable...

Special Considerations

Mineral oil, cholesterol-reducing drugs (such as cholestyramine and colestipol), the obesity drug Orlistat, Colchicine (used for treatment of gout), and regular use of plant sterol- or stanol-containing margarines have been shown to reduce carotenoid absorption from food sources and supplements. There is some evidence that alcohol may also inhibit ( -carotene conversion to retinol.

Proteincoated artificial cells in immunoadsorption

Albumin can bind tightly to the ultrathin collodion membrane of adsorbent artificial cells, and was initially used to increase the blood compatibility of the adsorbent artificial cells for hemoperfusion (Chang, 1969a). This albumin coating has also been applied to synthetic immunosorbents, resulting in blood compatible synthetic blood group immunosorbents (Chang, 1980d). The albumin-coated synthetic adsorbent has been applied clinically for removing blood group antibodies from plasma for bone marrow transplantation (Bensinger et al., 1981). In addition, albumin-coated collodion activated charcoal (ACAC) was found to effectively remove antibodies to albumin in animal studies (Terman et al., 1977). This principle has become a basis of one line of research in which other types of antigens or antibodies are applied to the collodion coating of the activated charcoal to form immunosorbents. Other immonosorbents based on the same principle have also been developed for the treatment of human...

Digestion of Cholesteryl Ester

The bulk of dietary cholesterol intake occurs as the absorbable, free sterol form, with only 10 to 15 occurring as CE, which must first be hydrolyzed to free cholesterol prior to absorption (87). Pancreatic cholesterol esterase (3.1.1.13), also known as carboxylic ester hydrolase or sterol ester hydrolase, has been purified from porcine (88,89), rat (90), and human pancreas (91,92) and rat, bovine, and human pancreatic cholesterol esterases have been cloned (93-95). Human and rat cholesterol esterases have molecular weights of about 100 kDa and 70 kDa, respectively, and share 78 structural homology (90,91). Using site-directed mutagenesis, DiPersio et al. (96) demonstrated that substitution of threonine or alanine for serine at position 194 in rat cholesterol esterase abolished enzymatic activity. Using a similar approach, DiPersio et al. (97) further demonstrated that, in addition to serine, histidine in position 435 and aspartic acid (98) at position 320 formed a triad of amino...

Vitamins and Memory Function New Results from the Basel Longitudinal Project IDA

High systolic blood pressure is one of the major risk factors for stroke and vascular dementia (Binswanger disease). High cholesterol is also related to stroke, TIA, and indirectly reflects apoEe4 status. Thus, both are to some extent risk-related to cognitive function and dementia. They therefore have to be allowed for in evaluating the effect of antioxidants on cognitive functioning. Ferritin is an indicator of tissue iron stores and thus of the pro-oxidative potential in the presence of free radicals (Volicer and Crino, 1990 Evans, 1993). In addition, ascorbic acid may have pro-oxidative activity in the presence of high endogenous ferritin content (Sram et al., 1993). Thus, since these measurements were available for 1971 and 1993, it was important to include them in the analyses.

Spinal cord stimulation

Spinal cord stimulation (SCS) has been used since the early 1970s and applied to refractory angina pain since 1985.38 Studies have shown improved quality of life,31,32,35,38 reduction in hospital admission rates,33,38 comparable mortality for patients with similar degree of coronary artery disease, and symptoms controlled by medical or surgical means.31,5556 Studies have also demonstrated that these do not mask the symptoms of an acute coronary event.33 A review by a Working Group of the European Society of Cardiology recommend spinal cord stimulation treatment for refractory angina pectoris.34 V Despite evidence in favor of the use of spinal cord stimulators, they are only effective in around 75 percent of patients with refractory angina pectoris.19,57 Factors predictive of good outcome have been suggested as left ventricular ejection fraction > 40 percent, low cholesterol levels, fewer attempts at revascularization before the procedure, and a lower New York Heart Association...

Industrial Applications

Lipases have been utilized to hydrolyze triglycerides into diglycerides, mono-glycerides, fatty acids and glycerol (Houde et al., 2004). Lipases are a subset of esterases. The detergent industry utilizes lipases to remove fat containing stains and formulates them at pH extremes in the presence of surfactants (Houde et al., 2004). The active site contains an Ser-His-Asp(Glu) catalytic triad that is shielded from the solvent by a flap (Gonzales-Navarro et al., 2001 Houde et al., 2004 ). In an aqueous environment, the flap is closed. When bound to a lipid, or other interface, the flap is open and the active size is exposed to the solvent (Gonzales-Navarro et al., 2001). Researchers have utilized the concept of molecular memory to kinetically trap (freeze-drying) the enzyme conformation in its activated form and subsequently utilizing it in an organic media (Gonzales-Navarro et al., 2001). The benefits of utilizing an organic solvent include stabilizing the transition state and minimizing...

Drug And Other Interactions

The list of drugs and other factors that may affect the action of oral anticoagulants is prodigious. Any substance or condition is potentially dangerous if it alters (1) the uptake or metabolism of the oral anticoagulant or vitamin K (2) the synthesis, function, or clearance of any factor or cell involved in hemostasis or fibrinolysis or (3) the integrity of any epithelial surface. Patients must be educated to report the addition or deletion of any medication, including nonprescription drugs, herbal remedies and food supplements. Some of the more commonly described factors that cause a decreased effect of oral anticoagulants include reduced absorption of drug caused by binding to cholestyramine in the GI tract increased volume of distribution and a short t 2 secondary to hypoproteinemia, as in nephrotic syndrome increased metabolic clearance of drug secondary to induction of hepatic enzymes, especially CYP2C9, by barbiturates, carbamazepine, or rifampin ingestion of large amounts of...

Exopolysaccharide Biosurfactants

The exopolysaccharide biosurfactants form an important group of marine biosurfactants. Microbial genera such as Alcaligenes, Pseudomonas, Halomonas and Antarctobacter have been reported as the main producers of this type of biosurfactants. For example, tetradecan degrading Alcaligenes sp. PHY 9L.86 was isolated from hydrocarbon polluted sea-surface water. This marine bacterium produced surface active exopolysaccharides (extracellular carbohydrates) and lipids which caused foam formation and emulsification of the culture medium.9 The extracellular lipid concentration was found to attain a maximum value of 7.91 mg L-1 in the early stationary phase, whereas maximum concentration of exopolysaccharides reached 12.63 mg L-1 at the stationary phase. The extracellular lipids produced by this strain was composed mainly of phospholipids, free fatty acids, triglycerides, monoglycerides and wax esters amongst which the percentage of free fatty acids (73 ) was the highest. Electron microscopy...

Surface Properties of Artificial Cell Membranes

Albumin can bind tightly to the ultrathin collodion membrane of adsorbent artificial cells. This is initially used to increase the blood compatibility of the adsorbent artificial cells for hemoperfusion (Chang, 1969a). This albumin coating has also been applied to synthetic immunosorbents, resulting in blood compatible synthetic blood group immunosorbents (Chang, 1980d). In addition, Terman etal. (1977) showed in animal studies that albumin-coated collodion activated charcoal (ACAC) can remove antibodies to albumin. This has become a basis of one line of his research in which other types of antigens or antibodies are applied to the collodion coating of the artificial cells to form immunosorbents. Other immunosorbents based on this principle have also been developed for the treatment of human systemic lupus erythematosus removal of antiHLA antibodies in transplant candidates treatment of familial hypercholesterolemia with monoclonal antibodies to low-density lipoproteins (Terman, 1980

Metabolic And Cardiovascular Effects

Although they may slightly elevate plasma triglycerides, estrogens generally have favorable overall effects on plasma lipoprotein profiles. However, concurrent administration of progestins may reduce these favorable actions. Currently prescribed doses of estrogens do not increase the risk of hypertension.

HDLAtherosclerosis Treatment Study HATS

In this 3-y, double blind study, 160 patients with CAD and low HDL-cholesterol (women and men, values < 40 and 35 mg dL, respectively) were entered into the study (27). Coronary artery disease was defined as previous MI, coronary interventions, or confirmed angina and with at least 3 stenoses of at least 30 of the luminal diameter or 1 stenosis of at least 50 . The four groups included a placebo group, a group that received simvastatin and niacin, an antioxidant group, and a simvastatin, niacin, and antioxidant group. The antioxidant supplement that was given twice daily resulted in doses of 800 IU d of RRR-AT, 1000 mg d of vitamin C, 25 mg d of p-carotene, and 100 g d of selenium. The patients were followed up for 3 y and the end point was arteriographic evidence of a change in coronary stenosis and occurrence of a first cardiovascular event (death, MI, stroke, and revascularization). The average age of the patients was 53 y, and 13 were women. The antioxidant supplementation...

Other medicinal benefits

Dietary fibers support to reduce cholesterol levels and recent studies have shown that dietary fibers with ion-exchange capacity contain more potent effects on cholesterol lowering (Guillon and Champ, 2000). Ulvan, which belongs to the SP group from Ulva pertusa, is a potential antihy-perlipidemic agent and has significantly reduced serum triglyceride (TG), total and low-density lipoprotein cholesterol (LDL-cholesterol), and elevated high-density lipoprotein cholesterol (HDL-cholesterol) in mice (Yu et al., 2003a). According to Yu et al. (2003b), antihyperlipidemic activity of ulvan depends on the molecular weight of ulvan fractions high molecular weight fraction is more effective on serum total and LDL-cholesterol, whereas low molecular weight fractions are more effective on TG and HDL-cholesterol. Ulvan contains uronic acid and sulfates, with potential capability of sequestering or binding bile acids (Lahaye, 1991).

Broad Range of Genetic Diversity Impinges on Statin Hypolipidemic Therapy

Several large, multicenter trials have demonstrated that statin therapy reduces both primary and secondary coronary artery disease. Worldwide, the statins represent one of the most widely prescribed classes of drugs. Although they interact with a variety of cellular processes, the statins derive their primary therapeutic effect by attenuating lipoprotein synthesis and upregulating the expression of low-density li-poprotein cholesterol receptors. Currently, there are at least half a dozen statin drugs on the market, and despite their clinical efficacy, statin therapy can be complicated by differential properties of individual statins. Some are highly lipophilic while others are hydrophilic, and the resultant profiles differ from one statin to another. Wilke et al.59,79 have summarized the pharmacokinetics of several statins of particular interest. Each of three common Phase I enzymes, CYP2C9, 2D6, and 3A4 5, interacts differently with each of the currently available statins....

Capsules Filled with Liquids and Semisolid Matrices

LBDDSs are complex compositions of three main classes of components lipids, surfactants, and cosolvants (196). The lipid component may be a single lipid or a blend of fatty materials. The most important lipids in this application are fatty acids or their derivatives (e.g., mono-, di- and triglycerides, propylene glycol esters). These can be either solid or liquid at room temperature, depending on such factors as their chain length and degree of unsaturation of the fatty acid chains. Lipid-based formulations frequently also include a surfactant (emulsifier) to assist in the breakup and dispersion of the capsule content in gastrointestinal fluids. Typically, these are nonionic surfactants (e.g., polyoxyl 40 stearate, polysorbate 80, and sorbitan monopalmitate) of varying hydrophilic-lipophilic balance (HLB). Lipid-based systems may also include cosolvants (e.g., alcohol, PEG 400, 1. Water immiscible, volatile or more likely nonvolatile liquids such as vegetable oils, aromatic and...

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