Improve Cholesterol Levels with These Super Foods

Beat Cholesterol By Scott Davis

Since Scott Davis released the Beat Cholesterol In 30 Days program, many people used it to learn how to manage their hypercholesterolemia quickly and naturally. Due to his personal fight with the disease and the desire to completely avoid prescription meds, he discovered the most effective techniques to overcome this condition and live longer, happier life. Davis discovered that cholesterol medications dont work, and are actually harmful. Statins such as Lipitor can cause brain damage, may actually increase your risk of a heart attack and can also cause kidney damage. Thats a lot of scary side effects for a drug that is supposed to help you. Like all the other Blue Heron Health News promoted health guides, the Beat Cholesterol in 30 Days guidebook will help you achieve better health using an all-natural method. Unlike most prescription drugs, this program ensures a risk-free solution to a reduced cholesterol level in a short span of time. This book will provide you with all there is to know about your silent killer enemy: cholesterol. Read more here...

Natural Cholesterol Guide Summary

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My Natural Cholesterol Guide Review

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Nicotinic acid and cholesterol levels

Niacin is an over-the-counter medication that is arguably the best cholesterol-lowering agent available. In its new formulation, it is safe, inexpensive and effective. It has proved to significantly increase high-density lipoprotein cholesterol (HDL-C) with greater effectiveness than any other medication. In addition, it decreases total cholesterol, low-density lipoprotein cholesterol (LDL-C), lipoprotein (a) and triglycerides.27,35 Niacin has also recently been used in combination with other medications such as lovastatin and, because of their different mechanisms of action, cholesterol profile has improved more than with one medication alone.34,36

Serum cholesterol levels

Ingestion of the high-fat diet led to a marked elevation of serum LDL and VLDL cholesterol from 10.9 to 93.8 mg dl (Table 1). Taurine treatment decreased serum LDL and VLDL cholesterol levels by 49 . Although serum HDL cholesterol tended to decrease by ingestion of the high-fat diet, taurine significantly increased serum HDL cholesterol. Table 1. Effect of taurine on body weight and serum cholesterol levels Table 1. Effect of taurine on body weight and serum cholesterol levels

Regulation of Energy Release from Triglycerides

Carbohydrates Are Preferred over Fats for Energy When Excess Carbohydrates Are Available. When excess quantities of carbohydrates are available in the body, carbohydrates are used preferentially over triglycerides for energy. There are several reasons for this fat-sparing effect of carbohydrates. One of the most important is the fol-lowing The fats in adipose tissue cells are present in two forms stored triglycerides and small quantities of free fatty acids. They are in constant equilibrium with each other.When excess quantities of a-glycerophosphate are present (which occurs when excess carbohydrates are available), the excess a-glycerophosphate binds the free fatty acids in the form of stored triglycerides. As a result, the equilibrium between free fatty acids and triglycerides shifts toward the stored triglycerides consequently, only minute quantities of fatty acids are available to be used for energy. Because a-glycerophosphate is an important product of glucose metabolism, the...

Use of Triglycerides for Energy Formation of Adenosine Triphosphate

About 40 per cent of the calories in a typical American diet are derived from fats, which is almost equal to the calories derived from carbohydrates. Therefore, the use of fats by the body for energy is as important as the use of carbohydrates is. In addition, many of the carbohydrates ingested with each meal are converted into triglycerides, then stored, and used later in the form of fatty acids released from the triglycerides for energy. Hydrolysis of Triglycerides. The first stage in using triglycerides for energy is their hydrolysis into fatty acids and glycerol. Then, both the fatty acids and the glycerol are transported in the blood to the active tissues, where they will be oxidized to give energy. Almost all cells with some exceptions, such as brain tissue and red blood cells can use fatty acids for energy. Synthesis of Triglycerides from Carbohydrates Whenever a greater quantity of carbohydrates enters the body than can be used immediately for energy or can be stored in the...

High Cholesterol Hypercholesterolemia and Hypothyroidism

Hypothyroidism can increase cholesterol in people whose cholesterol levels would ordinarily be normal while euthyroid. But if you have high cholesterol that predates your hypothyroidism, your already high cholesterol level can jump off the charts. High cholesterol is dangerous because the excess cholesterol in your blood can lead to narrowed arteries (ASCVD), which in turn can lead to a heart attack or stroke. In the absence of hypothyroidism, saturated fat (see Chapters 16 and 20) is often a culprit when it comes to high cholesterol, but the highest levels of cholesterol are the result of genetic features affecting the creation or disposal of cholesterol in the liver. Familial hypercholesterolemia refers to a genetic cause for high cholesterol that does not respond adequately to diet modification. Tbtal blood cholesterol levels are often provided as general guidelines only. You also have to look at the relative proportion of high-density lipoprotein (HDL) or good cholesterol...

Digestion of Triglycerides by Pancreatic Lipase By far the

Most important enzyme for digestion of the triglycerides is pancreatic lipase, present in enormous quantities in pancreatic juice, enough to digest within 1 minute all triglycerides that it can reach. In addition, the enterocytes of the small intestine contain still more lipase, known as enteric lipase, but this is usually not needed. End Products of Fat Digestion. Most of the triglycerides of the diet are split by pancreatic lipase into

Serum cholesterol reduction and risk of ischaemic heart disease

Log Odds Ratio

The randomised controlled trials of serum cholesterol reduction have been the subject of a number of meta-analyses1419 20 and much controversy. In conjunction with the review of the 10 prospective studies just described, the results of 28 randomised trials available in 1994 were summarised 14 this omits the results of trials of serum cholesterol reduction, notably those using statins, that have become available more recently. The aim was to quantify the effect of serum cholesterol reduction on the risk of ischaemic heart disease in the short term, the trials having an average duration of about five years. There was considerable clinical heterogeneity between the trials in the interventions tested (different drugs, different diets, and in one case surgical intervention using partial ileal bypass grafting), in the duration of the trials (0-3-10 years), in the average extent of serum cholesterol reduction achieved (0-3-1-5 mmol l), and in the selection criteria for the patients such as...

High Cholesterol

Hypothyroid people often have high cholesterol that can lead to a host of other problems, including heart disease. This should be controlled through diet until your thyroid problem is brought under control. It's generally recommended that anyone with high cholesterol be tested for hypothyroidism. Cholesterol-lowering medications should not be started unless the high cholesterol levels persist a few months after sufficient thyroid hormone replacement therapy. We discuss cholesterol more in Chapter 25.

Cardiovascular Changes

More severe or prolonged hypothyroidism could raise your cholesterol levels as well, and this can aggravate blockage of coronary arteries. In severe hypothyroidism, the heart muscle fibers may weaken, which can lead to heart failure. This scenario is rare, however, and one would have to suffer from severe and obvious hypothyroid symptoms long before the heart would be at risk.

Confidence intervals for other parameters 321 Difference between two means

At the end of the previous chapter we saw how to extend the idea of a standard error for a single mean to a standard error for the difference between two means. The extension of the confidence interval is similarly straightforward. Consider the placebo controlled trial in cholesterol lowering described in Example 2.3 in Chapter 2. We had an observed difference in the sample means x1 x2 of 1.4 mmol l and a standard error of 0.29. The formula for the 95 per cent confidence interval for the difference between two means 2) is

How Much Physical Activity is Beneficial for Subjects with the Metabolic Syndrome

To answer this question we have recently examined the 2-year impact of different increments in EE through leisure-time physical activity on several physiological and biochemical outcomes, on direct medical costs and on direct and indirect social costs in a group of type 2 diabetic subjects who were randomized to a physical activity counseling intervention 12 . The intervention resulted in remarkable cost savings health benefits and financial advantages were significantly related to increased amounts of EE. Our results confirmed that the advice of several scientific societies 1-4,29 recommending 30 min or more moderate-intensity physical activity ( 10 METs h week) on most days, if not every day, is also valid for type 2 diabetic subjects and demonstrate a significant dose response relationship. Post-hoc analysis showed that EE must be 10 METs h week for significant beneficial effects. In fact, EE ranging between 11 and 20 METs h week significantly reduced HbA1c, total cholesterol,...

Dimensions of external validity

External validity relates to the applicability of the results of a study to other populations, settings, treatment variables, and measurement variables .14 External validity is a matter of judgement which will depend on the characteristics of the patients included in the trial, the setting, the treatment regimens tested, and the outcomes assessed (Box 5.1).14 In recent years large meta-analyses based on individual patient data have demonstrated that important differences in treatment effects may exist between patient groups and settings. For example, antihypertensive treatment reduces total mortality in middle-aged hypertensive patients40 but this may not be the case in very old people.41 The benefits of fibrinolytic therapy in suspected acute myocardial infarction has been shown to decrease linearly with the delay between the start of symptoms and the initiation of treatment.42 In trials of cholesterol lowering the benefits in terms of reduction of non-fatal myocardial infarction and...

The Insulin Connection

It is impossible to live without it, but it is possible to live much better without too much insulin. Insulin has many actions, but some of the most important affect body fat, cholesterol levels, and cardiovascular health. Insulin y promotes storage of free fatty acids as triglycerides (fat) and fat cells

Tolerance of Nicotinic Acid

Large doses of nicotinic acid have been used to bring about changes in cholesterol levels for more than 50 years,32 despite annoying side effects. Flushing, a reddening of the skin with the sensation of heat or itching, is the most common side effect. This flushing response mainly affects the upper body and face, occurring 1 to 2 h after ingestion, and the symptoms usually disappear after repeated nicotinic acid administration. Reduced oral glucose tolerance has also been commonly reported in the past with ingestion of nicotinic acid, but recent evidence demonstrates that niacin can be used safely and effectively in diabetics who have good glucose control.33,34 Although the use of pharmacologic doses of niacin have been associated with adverse side effects like flushing, liver dysfunction and gastrointestinal stress, newer formulations of niacin (extended-release) demonstrate minimal side effects with comparable effectiveness.35

Summary And Recommendations For Exercise And Sports Performance

Although niacin has an important role in energy metabolism, few studies cite enhanced performance with administration of small amounts of niacin. Frankau8 used 40-50-mg doses of nicotinamide and reported improved performance in an agility test. Hilsendager and Karpovich9 showed no effect of 75 mg of niacin on a cycle or hand ergometer endurance test, and there certainly has been no research to show improved performance with doses of nicotinic acid large enough to impact cholesterol levels (3 g d is the typical dose).

How Does Alcohol Reduce the Risk of Heart Disease

We have identified many of the biologic and physiologic effects of wine and alcohol that relate to protection against CAD. Alcohol affects blood lipids it increases HDL-cholesterol, the good cholesterol that lowers the risk of heart disease. Alcohol also tends to slightly decrease LDL-cholesterol, the bad cholesterol that increases atherosclerosis. Thus, individuals who have consumed moderate amounts of alcohol for most of their adult years tend to have less atherosclerosis.

Metaregression examining gradients in treatment effects

The clinical trials included in a meta-analysis often differ in a way which would be expected to modify the outcome. In trials of cholesterol reduction the degree of cholesterol lowering attained differs markedly between studies, and the reduction in coronary heart disease mortality is

Risk stratification in metaanalysis

A factor which is often related to a given treatment effect is the underlying risk of occurrence of the event the treatment aims to prevent. It makes intuitive sense that patients at high risk are more likely to benefit than low risk patients. In the case of trials of cholesterol lowering, for example, the patient groups have ranged from heart attack survivors with gross hyper-cholesterolaemia, to groups of healthy asymptomatic individuals with moderately elevated cholesterol levels. The coronary heart disease death rates of the former group have been up to 100 times higher than the death rates of the latter groups. The outcome of treatment in terms of all-cause mortality has been more favourable in the trials recruiting participants at high risk than in the trials involving relatively low-risk individuals.17 There are two factors contributing to this. First, among the high-risk participants, the great majority of deaths will be from coronary heart disease, the risk of which is...

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...

Hepatic enzyme activity

Effect oftaurine on liver cholesterol content. C57BL 6J mice consumed a high-fat diet for 6 months (HF) and the control group (C) consumed regular chow. Taurine was dissolved in drinking water at 1 (w v), and provided during ingestion ofregular chow (C+T) or the high-fat diet (HF+T). Cholesterol levels were measured enzymatically using commercial kits after extraction with isopropanol. Each value represents the mean SEM for data obtained from 9 mice. Significant difference ***p

Results And Discussion

The various diets listed in table 1 did not affect body weight gain nor did they modify food consumption (Table 2). However, liver weight was significantly increased by high fat high cholesterol diet, either alone or supplemented with taurine (Table 2). After feeding these diets for 14 days, plasma was taken from vena cava, and lipids were examined by enzymatic methods. Total cholesterol was markedly increased in animals fed on high fat high cholesterol diet. Taurine, however, significantly and dose-dependently, counteracted this effect, although it did not (Table 3) modify total cholesterol level in animals fed on a normal diets. HDL-cholesterol level was also increased by high fathigh cholesterol diet, but taurine had no influence upon it (Table 3). Taurine was also able to counteract drastically in a dose dependent fashion the effect of high fat high cholesterol diet on triglycerides which resulted markedly elevated as compared to values found in animals fed on a normal diet (Table...

Taurine Reduces Atherosclerotic Lesion Development In Apolipoprotein Edeficient Mice

Abstract The effects of dietary taurine on development of atherosclerotic lesions were investigated using apolipoprotein E (apoE)-deficient mice. Taurine added to regular chow at 2 (w w), was made freely available to mice for 3 months. Severe hypercholesterolemia and development of atherosclerotic lesions occurred in the apo-E-deficient mice. Taurine treatment decreased the area of Oil red-O positive lipid accumulation in the aortic valve by 31 . In contrast, taurine significantly increased serum atherogenic lipoproteins (LDL + VLDL), without changing HDL cholesterol levels. Although the levels of serum thiobarbituric acid reactive substances (TBARS) in apoE-deficient mice were significantly higher than in wild-type mice, taurine decreased TBARS by 26 . These observations mean that taurine prevents the development of atherosclerosis, independent of serum cholesterol levels. We suggest that anti-oxidative actions may be involved in the anti-atherosclerotic effects of taurine.

Statistical methods for investigating sources of heterogeneity

To be explicit, consider the analysis presented in Figure 9.5. Here there are 28 trials, which we index by i 1 28. For the ith trial, we denote the observed log odds ratio of ischaemic heart disease by yi, its estimated within-trial variance by v., and the extent of serum cholesterol reduction in mmol l by x The linear regression of log odds ratios on extent of cholesterol reduction can be expressed as y. a + fix. here we are not forcing the regression through the origin as in Figure 9.5, and a represents the intercept of the regression line. The purpose of the analysis is to provide estimates of a and fi, together with their standard errors. An additional point of interest is the extent to which the heterogeneity between results is reduced by including the covariate. The weights for the regression are equal to 1 (v + T2), where T2 is the residual heterogeneity variance. There are a number of ways of estimating T2, amongst which a restricted maximum likelihood estimate is generally...

Asymmetry is not proof of bias alternative sources of funnel plot asymmetry

The trials displayed in a funnel plot may not always estimate the same underlying effect of the same intervention and such heterogeneity between results may lead to asymmetry in funnel plots if the true treatment effect is larger in the smaller trials. For example, if a combined outcome is considered then substantial benefit may be seen only in patients at high risk for the component of the combined outcome which is affected by the intervention.17,18 A cholesterol-lowering drug which reduces coronary heart disease (CHD) mortality will have a greater effect on all cause mortality in high risk patients with established cardiovascular disease than in young, asymptomatic patients with isolated hypercholesterolemia.19 This is because a consistent relative reduction in CHD mortality will translate into a greater relative reduction in all-cause mortality in high-risk patients in whom a greater proportion of all deaths will be from CHD. Trials conducted in high-risk patients will also tend to...

Examining biological plausibility

In some circumstances, the possible presence of bias can be examined via markers of adherence to treatment, such as metabolites of a drug in patients' urine, or of the biological effects of treatment such as the achieved reduction in cholesterol in trials of cholesterol-lowering drugs, which, as discussed in Chapter 9, predicts the reduction in clinical heart disease24,25 and mortality.25

Endothelial Progenitor Cells

Differentiation of organs depends on signals derived from developing vasculature. Embryonic endothelial progenitor cells (EPCs), angioblasts, arise from migrating mesodermal cells and have a precursor in common with hematopoietic stem cells (hemangioblasts, HSCs). These cells appear together during formation of blood islands and the yolk sac capillary network with the EPCs located peripherally to the HSCs. EPCs respond to fibroblast growth factor-2, and vascular endothelial growth factor (VEGF). Activation of vasculoneogenesis in the adult in response to hyperplasia, injury, or tumor growth involves both endothelial cells in situ and circulating EPCs from the bone marrow. Bone marrow-derived EPCs may be mobilized by growth factors such as granulocyte macrophage colony-stimulating factor and VEGF. The therapeutic use of EPCs became feasible when it was shown that statins activate EPCs and enhance angiogenesis in vivo. In addition, mobilized EPCs may be expanded in vitro and used for...

Problems in Taking T4 Other Drugs or Supplements That Interfere

A few medications are infamous for interfering with your T4 treatment. Sucralfate is used to coat your stomach to treat irritation or ulcers, and it can keep T4 from being absorbed into your body. Cholestyramine and colestipol (used to treat high cholesterol levels) and high doses of antacids (aluminum and magnesium hydroxides) also keep T4 from getting absorbed properly. Liquid soy preparations, often used as milk substitutes or for baby formulas, can also bind to T4 if taken in moderately large amounts within four hours of taking your T4 dose.

Hormonal Influences on Homeostatic Mechanisms

Insulin is secreted in response to increased levels of blood glucose. This may occur after a meal or if glucagon is released and circulating glucose increases. Increased insulin levels cause glucose to enter cells more quickly where it is either used for fuel or, in the case of fat cells, is converted to triglycerides and stored. Blood glucose levels then drop. Data support the contention that hunger and eating are initiated when nutrient levels, especially glucose levels, decrease in the blood. Thus a high insulin level could lead to hunger because it decreases blood glucose. Furthermore, insulin levels can be influenced by the hypothalamus, and disruption of this control by hypothalamic lesions may explain some of the effects of such lesions on eating behavior and body weight.

Management of Established Problems

And reducing substances, as well as the Schilling test. Bacterial contamination of the small bowel may also predispose to malabsorption strictures and blind loops can also contribute to this complication. Intubation and quantitative bacterial cultures of the small bowel may be required to confirm the diagnosis, especially in the absence of the ileocecal valve or in the presence of small bowel stasis. Bacterial overgrowth responds to appropriate antimicrobial therapy, such as tetracycline or metronidazole. Chronic diarrhea associated with bile salt malabsorption after ileal resection may improve with cholestyramine. Refractory malabsorption associated with villous atrophy may require enteral or parenteral nutritional support.

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...

Absorption And Metabolism Of Vitamin A

Preformed vitamin A is usually ingested in the form of retinyl esters. These esters are hydrolyzed in the intestinal lumen together with triglycerides by various pancreatic ester hydrolases,13 and the resulting retinal is very efficiently absorbed by the intestinal mucosa. Inside enterocytes, provitamin A carotenoids are partially converted to retinal by central cleavage enzyme (15,15'-monooxygenase) or asymmetrically degraded to retinal by other enzymes.14,15 These enzymes may be also expressed in other tissues (liver, kidney, testes), possibly producing limited amounts of vitamin A from locally stored carotenoids.16 Retinal is immediately reduced to retinol, but a small percentage may be oxidized to retinoic acid. In the intestinal cell, both the absorbed and the newly formed retinol form a common pool, rapidly esterified by long-chain fatty acids and incorporated into chylomi-crons. Chylomicron particles, composed mainly of triglycerides, transport retinyl esters and the...

Water Insoluble Organic Solvents and Solids

A lipid-based oral formulation is used for water-insoluble drugs in cases where typical formulation approaches (i.e., solid wet granulation, solid dry granulation, water-soluble liquid in a capsule) do not provide the required bioavail-ability, or when the drug itself is an oily substance (e.g., dronabinol, ethyl icosapentate, indomethacin farnesil, teprenone, and tocopherol nicotinate). The water-insoluble solvents used in commercially available solubilized oral formulations include oleic acid, dl-a-tocopherol (Vitamin E), medium-chain mono-and diglycerides, long-chain triglycerides (peanut oil, corn oil, soybean oil, sesame oil, olive oil, peppermint oil, and castor oil), medium-chain triglycerides derived from coconut oil and palm seed oil, mono- and diesters of propylene glycol, or monoesters of glycerol. Medium-chain triglycerides are commonly used to solubilize water-insoluble drugs. The mixture of ethanol and fractionated medium chain triglyceride of coconut oil is sometimes...

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...

Recent Advances since the Edmonton Protocol

Marginal mass islet model in mice, as well as antioxidant therapy with nicotinamide, vitamin D3, pentoxiphylline or cholesterol lowering agents pravastatin or simvastatin, have all demonstrated positive impact in the pre-clinical setting, and suggest a potential role in future clinical trials designed to improve islet engraftment.

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.

Abetalipoproteinemia Bassen Kornzweig Syndrome

This autosomal recessive lipid disorder develops clinically in the first decade of life with steatorrhea, distal sensorimotor neuropathy, and retinitis pigmentosa. Ataxia, dysarthria, areflexia, and ophthalmoparesis may also develop. y Serum cholesterol levels are low, betalipoproteins are low or absent, and erythrocytes take on the appearance of acanthocytes. The primary metabolic defect relates to the inability to synthesize betalipoprotein, the major protein of chylomicrons and very low density lipoproteins. Because of the reduced chylomicrons, severe deficiencies of fat-soluble vitamins, namely A, K, and E, occur. Systemic signs can include cardiomyopathy. The differential diagnosis includes disorders that have combined neuropathy and ataxia, and include Friedreich's disease and the hereditary sensorimotor neuropathies. Laboratory analysis and EMG studies suggesting axonal neuropathy are helpful in directing the clinician. y The differential diagnosis also includes those disorders...

The Hypothyroid Obese Individual

Hypothyroidism can cause or aggravate hypertension and high cholesterol, which are risk factors for cardiovascular disease and can also lead to atherosclerosis (clogged arteries) and congestive heart failure, discussed in Chapter 25. When type 2 diabetes is in the picture, some individuals may need to be on more intensive diabetes control and may even require insulin, since hypothyroidism can affect blood sugar control, which in turn increases the risk of heart attack and stroke. Although lifestyle changes, combined with restored thyroid function, can normalize blood pressure and cholesterol levels in many cases, blood pressure and cholesterol-lowering medications may be necessary, discussed in Chapter 25.

Lowering Fat and Healthy Eating

Dietary guidelines from nutrition experts, government nutrition advisories and panels, and registered dieticians have not changed in fifty years. A good diet is a balanced diet representing all food groups, based largely on plant foods, such as fruits, vegetables, legumes, and grains (also known as carbohydrates), with a balance of calories from animal-based foods, such as meats (red meat, poultry), fish, and dairy (also known as protein and fat). Nutrition research spanning the last fifty years has only confirmed these facts. What has changed in fifty years is the terminology used to define good diet, and the bombardment of information we receive about which foods affect which physiological processes in the body, such as cholesterol levels, triglycerides, blood sugar levels, and insulin. There are also different kinds of fats and carbohydrates, which

Andrea J Young MDa David R McAllister MDb

Many individuals participate in recreational and professional activities each year. The health benefits are many improved cardiovascular structure and decreased body weight, cholesterol, triglycerides, glucose, and systemic blood pressure. With the beneficial health effects, however, come overuse injuries. Stress fractures are a relatively common injury in athletes, and the amount of time lost from sports can be considerable. Stress fractures can have devastating consequences, even when they are treated.

Combination Antihypertensive Agents

Although all three of the broad categories of antihypertensive medications have been shown to reduce blood pressure, several possess physiological or metabolic side effects that are associated with increased risk for other pathological conditions. Already mentioned is the potassium-depleting characteristic of thiazide and loop diuretics, which results in an increased risk for arrhythmias and other metabolic disturbances. Similarly, beta-blockers have been shown to raise triglycerides and alter one's lipid profile (Kaplan, 2002). Because multiple antihy-pertensive agents may be needed to achieve optimal blood pressure control and to counteract some of the negative side effects associated with taking a single antihypertensive agent, many combination drugs

Warm Stains Cold Hits

Ples include the body mass index (BMI), cholesterol levels (HDLs and LDLs), blood pressure, and sperm counts. These clinical gazes assume some desirable number that is equivalent to a desirable physical or mental trait any deviation from the desirable number is considered a problem and often results in further testing. These numbers are also used in larger databases to determine trends in populations and policies for controlling these populations. These systems of standardization thus became means of social power and produce a socially controlling environment.

Viiiinfections Hsp And Atherosclerosis

It is also known that atherosclerotic lesions emerge in children as early as at 10-12 years of age (24), and the blood cholesterol concentration alone is not a plausible explanation, since most of these children have normal or even relatively low blood cholesterol levels. Alternatively, various microbial infections, such as those mentioned above, are frequent in children and may play a part in initiating atherosclerosis, although no causal relationship has yet been established between specific infections and atherosclerosis.

The Importance of Replication

These findings for women and patients with baseline LDL cholesterol 125 mg dl were obtained from the CARE clinical trial and published by Sacks et al. 2 , producing much discussion among lipidologists. A follow-up manuscript elaborating on the effect of cholesterol reduction therapy in women was published by Lewis et al 6 . A manuscript examining the relationship between LDL cholesterol and clinical endpoints was also published in 1998 7 . The subgroup findings from CARE and the subsequent published manuscripts based on these findings were surprising and useful, generating much debate. In neither case was the hypothesis stated prospectively (with alpha allocation) in the protocol.* Yet, in each case the subgroup analysis was relevant and insisted upon by the scientific community. How can one interpret the findings of these required but non-prospective evaluations

Evaluation of Nutritional Status using Biochemical Assessment

Lesterol, low-density lipoprotein cholesterol and triglyceride levels are generally observed in exercising adults as compared with values when they were more sedentary 1 . Possible lipid oxidation may also result from ultra-endurance activities 32 . Changes in cholesterol ester transfer protein and lecithin-cholesterol acyltransferase appear to be consistent with increased high-density lipoprotein cholesterol levels 1,29 . Most of the studies were done in men it's unclear whether exercise intensity affects the lipid changes in women 1,3, 32 .

Describing the effects of treatment

Treatment with statins is associated with a relative risk of 0-69 for all cardiovascular disease (CVD) events (see Table 20.1). The likely risk of CVD in a high risk group of patients might be as high as 5 per year. This can be estimated from studies of prognosis in relevant patient groups

Effect Modification and Interactions

During the course of the trial the effect of the randomly allocated intervention pravastatin on lipids appeared to be the same in women and men, producing equivalent reductions in total cholesterol (20 in women, 19 in men), low density lipid (LDL) cholesterol (28 in women, 28 in men), and triglycerides (13 in women, 14 in men). There were also equivalent elevations in high-density lipoprotein (HDL) cholesterol (4 in women, 5 in men).

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...

Nutritional Assessment

Early studies involving humans seemed to indicate improved glucose tolerance following Cr supplementation43-45 but numerous methodological problems existed, like the lack of control or placebo groups, no blinding of the procedures and inconsistent findings. There were two early placebo-controlled, double-blinded studies46,47 in Type 2 diabetics however, both failed to demonstrate an effect on glucose tolerance or body weight and had only mixed results regarding an effect on lipid levels. Uusitupa et al.46 reported no change in serum total cholesterol and triglycerides and in high-density, low-density and very-low-density lipoprotein subfractions, whereas Abraham et al.47 reported increases in high-density lipoprotein levels and decreases in very-low-density lipoprotein cholesterol levels. The data are also conflicting and contradictory when examining the effects of Cr on lipid fractions. A few studies report elevated high-density lipoprotein cholesterol levels and significant...

Cardiovascular surgeon See cardiac surgeon

Cholesterol ratio Ratio of the total cholesterol measured in the blood to the amount of high-density lipoproteins (HDL). A high ratio of total cholesterol to HDL-cholesterol usually indicates greater risk for having coronary disease or a more rapid progression of existing coronary artery disease.

General Properties and Possible Metabolic Functions

There is considerable evidence that dietary nickel influences carbohydrate and lipid metabolism in experimental animals. Some of the first studies suggesting that nickel may be essential showed that rats fed a 0.015-mg Ni kg diet compared with those fed a 20-mg Ni kg diet had depressed activities of enzymes that degrade glucose to pyruvate and enzymes that produce energy through the citric acid cycle these enzymes included glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase and malate dehydrogenase.116 Also, glucose, glycogen and triglycerides were reduced in the liver, and ATP and glucose were reduced in serum of rats fed low dietary nickel.116 The amount of nickel fed to the supplemented controls was quite high relative to the suggested nickel requirement of rats of 0.15-0.2 mg kg diet.117 Because this high dietary concentration of nickel can affect iron metabolism in an apparent pharmacologic manner,118 uncertainty existed about whether the changes in carbohydrate and lipid...

Treating Heart Failure in Hypothyroidism

The first step in treating heart failure is to take the appropriate medications prescribed by your physician that decrease the workload of the heart and make it perform more efficiently. This includes reducing the peripheral vascular resistance (seen as high blood pressure or hypertension), decreasing the volume of blood backing up (by using diuretics), and taking medication that enhances the strength of the heart muscle. When hypothyroidism is present and contributing to the heart failure, treatment with thyroid hormone should be started as soon as possible however, it takes several weeks to fully take effect, and it is important to make sure that you are taking the proper heart medication in the meantime. It is very unusual for hypothyroidism, on its own, to be able to weaken the heart sufficiently to cause heart failure. This makes it very important to continue looking for primary heart problems and treat them in addition to treating the hypothyroidism. If you have underlying heart...

Pathophysiology Of Intestinal Insufficiency

By bacteria or drugs (e.g., cholestyramine), and interruption of the enterohepatic circulation by ileal disease or resection may all contribute to fat malabsorption.1 1 1 Bacterial overgrowth also disrupts intraluminal digestion.1 Finally, rapid intestinal transit causes malabsorption by shortening the time for intraluminal digestion to occur.

Diagnostic Evaluation Of Intestinal Insufficiency

Bile salt malabsorption can be evaluated by the 14 C-glycocholic acid breath test. This has a high false-positive rate and requires simultaneous measurement of breath and stool radioactivity to exclude bacterial overgrowth. In the clinical situation, a trial of cholestyramine therapy is often more useful. ' A positive response should be evident within a few days.

Hepatocyte Transplantation in Watanabe Hyperlipidemic Rabbits

The success of the above studies in Nagase analbuminemic rats encouraged us to use the same strategy in Watanabe heritable hyperlipidemic (WHHL) rabbits.14 The genetic defect in these animals is a counterpart of familial hypercholesterolemia in humans. Homozygous animals have a mutation in the low density lipoprotein (LDL) receptor gene and express almost no functional LDL receptors. As a result, intermediate density lipoproteins and LDL accumulate in the plasma, leading to accelerated atherosclerosis and premature death. Fig. 12.11. Serum cholesterol levels in the three groups of WHHL rabbits. Group I and II rabbits were transplanted (Tx.) with allogeneic hepatocytes. Group III controls received intraportal saline injection only. Portal branch ligation (PBL) was performed on day 7 posttransplantation in Group I and III animals. Baseline serum cholesterol levels were as follows Group I, 855 81 mg dl Group II, 843 102 mg dl Group III, 893 97 mg dl. Values are given as mean SD. * p 0.05...

Spontaneous Potentials Generated By Single Muscle Fibers 41 Fibrillation Potentials

Complex Repetitive Discharges

Myotonic discharges are helpful because they reduce the differential diagnosis of a patient presenting with symptoms of muscle disease. The list of disorders that are characterized by diffusely prominent myotonic discharges is relatively limited and includes myotonia con-genita, the myotonic dystrophies (types 1 and 2), paramyotonia congenital hyperkalemic paralysis, drug-induced myotonia (observed with colchicine, chloroquine, and with some cholesterol-lowering drugs). However, occasional myotonic discharges can also be present in patients with many other muscle diseases, including inflammatory myopathies, acid maltase deficiency (discharges are observed most prominently in the paraspinal muscles), myotubu-lar myopathy, and occasionally even in patients with neurogenic disease. It should be noted that, in some situations, muscle cooling can enhance the number of myotonic discharges, and applying ice to the skin overlying a muscle can sometimes be helpful.

Photosensitivity dermatoses

Pityriasis Rubra Pilaris Face Treatment

The diagnosis of a patient with a xanthoma would begin with tests for fasting plasma cholesterol and triglycerides. These tests should uncover 95 of the patients with hyperlipidemia. If these tests are abnormal, then plasma turbidity studies and plasma lipoprotein electrophoresis should be performed. On the basis of abnormal lipoprotein patterns, five types of familial hyperlipidemia can be recognized.

Thyroid Hormones Increase Active Transport of Ions Through

Activator Inhibitor

Increased thyroid hormone decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, even though it increases the free fatty acids. Conversely, decreased thyroid secretion greatly increases the plasma concentrations of cholesterol, phospholipids, and triglycerides and almost always causes excessive deposition of fat in the liver as well. The large increase in circulating plasma cholesterol in prolonged

Glucose Is Transported by a Sodium CoTransport Mechanism

After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell's smooth endoplasmic reticulum here, they are mainly used to form new triglycerides that are subsequently released in the form of chylomicrons through the base of the epithelial cell, to flow upward through the thoracic lymph duct and empty into the circulating blood. Direct Absorption of Fatty Acids into the Portal Blood. Small quantities of short- and medium-chain fatty acids, such as those from butterfat, are absorbed directly into the portal blood rather than being converted into triglycerides and absorbed by way of the lymphatics. The cause of this difference between short- and long-chain fatty acid absorption is that the short-chain fatty acids are more water-soluble and mostly are not reconverted into triglycerides by the endoplasmic reticulum. This allows direct diffusion of these short-chain fatty acids from the intestinal epithelial cells directly into the capillary blood of the...

Transport of Lipids in the Body Fluids

Transport of Triglycerides and Other Lipids from the Gastrointestinal Tract by Lymph The Chylomicrons As explained in Chapter 65, almost all the fats in the diet, with the principal exception of a few short-chain fatty acids, are absorbed from the intestines into the intestinal lymph. During digestion, most triglycerides are split into monoglycerides and fatty acids. Then, while passing through the intestinal epithelial cells, the mono-glycerides and fatty acids are resynthesized into new molecules of triglycerides that enter the lymph as minute, dispersed droplets called chylomicrons, whose diameters are between 0.08 and 0.6 micron. A small amount of apoprotein B is adsorbed to the outer surfaces of the chylomicrons. This leaves the remainder of the protein molecules projecting into the surrounding water and thereby increases the suspension stability of the chylomicrons in the lymph fluid and prevents their adherence to the lymphatic vessel walls. Most of the cholesterol and...

Thyrotoxicosis and Obesity

In most cases of thyrotoxicosis (see Chapter 4), some weight loss occurs as the body and metabolism speed up. This is why thyroid hormone used to be wrongly prescribed as a diet drug. However, the hidden danger of thyrotoxicosis in obese people is that it overworks the heart in particular, which can be catastrophic for obese individuals with cardiovascular complications. Palpitations (sometimes because of atrial fibrillation) and angina (both discussed more in Chapter 25) can greatly increase the chances of an obese individual with thyrotoxicosis suffering from a sudden heart attack the risk of this increases if type 2 diabetes or smoking is in the picture. In such individuals, steps can be taken to reduce the risk of heart attack. First, the individual will be put on a beta-blocker (see Chapter 11), which stops the palpitations by blocking adrenaline. Second, a doctor will treat the underlying cause of thyrotoxicosis (for example, reduce the dosage of thyroid hormone or treat any...

Metabolic Functions of the Liver

Gluconeogenesis in the liver is also important in maintaining a normal blood glucose concentration, because gluconeogenesis occurs to a significant extent only when the glucose concentration falls below normal. In such a case, large amounts of amino acids and glyc-erol from triglycerides are converted into glucose, thereby helping to maintain a relatively normal blood glucose concentration.

Nicotinic Acid And Substrate Availabilityperformance

These findings demonstrate that nicotinic acid has a significant effect on fat utilization at rest. Butcher, Baird and Sutherland38 revealed the manner by which nicotinic acid effectively suppresses fat metabolism. Adenosine 3', 5'-monophosphate (cyclic AMP) has been implicated as an intrac-ellular second messenger. A decrease in cyclic AMP, caused by nicotinic acid, blocks the breakdown of white adipose tissue triglycerides to FFA and glycerol. Madsen and Malchow-M0ller39 stated that nicotinic acid inhibited the stimulation of adenylcyclase in adipocytes, causing decreased intracellular concentrations of cyclic AMP, which interfered with the activation of hormone-sensitive lipase. Nicotinic acid also has a direct inhibiting effect on the hormone-sensitive lipase.

Effect Of Spirulina On Fatty Liver

In an animal model, fatty liver has been reported to be induced by a high cholesterol diet,100 a 60 fructose diet,101 carbon tetrachloride,102,103 and alloxan-induced experimental diabetes.105 The high fructose diet induces fatty liver because the rapid conversion of fructose to acyl-CoA or a-glycerophosphoric acid elevates plasma lipid level.110 Fructose has been reported to have less effect on lipoprotein lipase (LPL) activation111 and to promote the activities of fatty acid synthesis-related enzymes such as acetyl-CoA carboxylase,112,113 fatty acid synthetase,112-114 and malic enzyme.112 The effectiveness of administering Spirulina to an animal with high fructose diet-induced hyperlipidemia (probably fatty liver) appears to be demonstrated in hypolipidemic effect,115,116 reduced liver triacylglycerol, and hypocholesterolemia.101 The beneficial effect of Spirulina may derive from the activated LPL activities, which are determined using postheparin serum.116 Different extracts of...

Biased inclusion criteria

Once studies have been located and data obtained, there is still potential for bias in setting the inclusion criteria for a meta-analysis. If, as is usual, the inclusion criteria are developed by an investigator familiar with the area under study, they can be influenced by knowledge of the results of the set of potential studies. Manipulating the inclusion criteria could lead to selective inclusion of positive studies and exclusion of negative studies. For example, some meta-analyses of trials of cholesterol-lowering therapy104105 have excluded certain studies on the grounds that the treatments used appear to have had an adverse effect that was independent of cholesterol lowering itself. These meta-analyses have, however, included trials of treatments that are likely to favourably influence risk of coronary heart disease, independent of cholesterol lowering. Clearly such an asymmetrical approach introduces the possibility of selection bias, with the criteria for inclusion into the...

Medical Aspects of the ED Evaluation

Several chronic medical diseases impact negatively on male erectile function, again highlighting the need to ask about ED in men with these conditions. Newer areas of study include associations between ED and obesity, as well as ED, as the metabolic syndrome (Figure 6.3) 19 . Thus, those men with the metabolic syndrome may deserve an evaluation for male ED. The ATP-III guideline suggests a working definition of the metabolic syndrome that includes the presence of at least three of the following characteristics abdominal obesity, elevated triglycerides, reduced levels of high density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose. In particular, the cut off values are the following waist circumference greater than 102 cm in men and greater than 88 cm in women triglycerides 150mg L (1.69mmol L) HDL cholesterol less than 40mg L (1.04mmol L) in men and less than 50mg L (1.29mmol L) in women blood pressure greater than 130 85 mmHg fasting glucose greater than...

Effects Of Long Term Treatment With Taurine In Mice Fed A High Fat Diet

Abstract Hypocholesterolemic effects of taurine in rats fed a high-fat and high-cholesterol diet are well established. However, there are few studies on long-term effects of taurine on cholesterol metabolism. In the present study, taurine was dissolved in drinking water and given to C57BL 6J mice during 6 months-feeding of a high fat diet. Taurine treatment significantly decreased serum LDL and VLDL cholesterol, while it significantlyincreased serum HDL cholesterol. In the liver, taurine decreased cholesteryl ester contents, accompanied by decrease in acyl Co-A cholesterol acyltransferase (ACAT) activity. Hepatic activity of cholesterol 7a-hydroxylase, a rate-limiting enzyme for bile acid synthesis, was doubled with taurine. Taurine reduced by 20 the high-fat diet-induced arterial lipid accumulation. Thus, taurine prevented elevation of serum and liver cholesterol levels, as possibly related to accelerated cholesterol elimination from the body through the stimulation of bile acid...

Effects of Cortisol on Fat Metabolism

The mechanism by which cortisol promotes fatty acid mobilization is not completely understood. However, part of the effect probably results from diminished transport of glucose into the fat cells. Recall that a-glycerophosphate, which is derived from glucose, is required for both deposition and maintenance of triglycerides in these cells, and in its absence the fat cells begin to release fatty acids.

Trends in consumer preference

Chilled fresh pasta as representing a healthier and convenient meal source (Anonymous, 2000). Textural quality of these products remains important but can be influenced by the type of treatment used to prevent bacterial growth and maintain shelf life (Anonymous, 2003a,b). The trend to healthy diet has also led many consumers to look for new sources of dietary fibre. Soluble dietary fibre and P-glucan are reported to lower serum cholesterol levels and reduce the risk of cardiovascular diseases (Betschart, 1988 Bhatty 1993 Newman and Newman, 1991 Yokoyama et al., 1997). Research has shown that pasta can be prepared using mixtures of pearled barley fractions (Marconi et al., 2000), barley flour enriched with P-glucan (Knuckles et al, 1997) and naked oat flour (Sgrulletta et al., 2001). Barley has neutral flavour and texture properties (Pszczola, 2003) and consequently pasta with acceptable sensory properties can be produced. Textural properties are negatively influenced by the addition...

Risks of androgen therapy

Available data regarding the relation of T-replace-ment therapy to lipid profiles are inconsistent. Supraphysiologic doses of androgens, particularly oral non-aromatizable androgenic steroids, appear to lower HDL levels 195 . However, numerous controlled studies using physiologic doses of T have shown no change, or only a minimal reduction, in HDL, often accompanied by a reduction in total cholesterol. Whitsel et al. performed a meta-analysis of the effects of intramuscular T esters on serum lipids in men with hypogonadism, and reported that HDL levels were reduced in three studies and unchanged in 15 196 . Total cholesterol levels were reduced in five studies, increased in two, and unchanged in 12. LDL levels were unchanged or reduced in 14 of the 15 studies in which they were measured. Thus, the limited information available would suggest a neutral effect of T therapy on lipid profiles. A doubleblind, placebo-controlled study involving 108 healthy men receiving transdermal T failed...

Heart Related Diseases

Studies have clearly demonstrated a consistently positive relationship between increased serum cholesterol level in the form of low density lipoprotein and the rate of heart disease. At high levels the association is particularly strong. Good evidence exists that lowering cholesterol levels with drug therapy will lower death rates from coronary disease. Exercise, too, has a beneficial effect on the types of lipids circulating in the bloodstream.

Physiology of Salivary Glands

Abdominopelvic Cavity

Saliva plays a crucial role in the digestion of carbohydrates and fats through two main enzymes. Ptyalin is an a-amylase in saliva that cleaves the internal a-1,4-glyco-sidic bonds of starches to yield maltose, maltotriose, and a-limit dextrins. This enzyme functions at an optimal pH of 7, but rapidly denatures when exposed to a pH less than 4, such as when in contact with the acidic secretions of the stomach. Up to 75 of the carbohydrate content in a meal, however, is broken down by the enzyme within the stomach. This is due to the fact that a significant portion of an ingested meal remains unmixed within the oral region, and thus there is a delay in the mixture of gastric juices with the food bolus. Starch digestion is not slowed in the absence of ptyalin because pancreatic amylase is identical to salivary amylase and is thus able to break down all carbohydrates when in the small intestine. The salivary glands of the tongue produce lingual lipase, which functions to break down...

Table 305 Glycogenoses

These diagnoses can usually be made by performing assays of enzymatic activity in the particular tissue most affected, such as the liver, peripheral white cells, muscle, and even brain. Since severe hypoglycemia is the best screening indicator of this class of disease, postprandial and glucose tolerance tests are particularly useful. A variety of other biochemical tests, such as uric acid, cholesterol, fatty acids, triglycerides, lipid profiles, and liver function tests, should be performed, as well as bone studies in specific instances. Management, Prognosis, and Future Perspectives. Therapy varies depending on the particular syndrome involved. In Von Gierke's disease, small amounts of free glucose can be given to maintain normal glucose concentrations dietary carbohydrates are also given, but because excessive glucose leads to glycogen storage in the liver and kidneys, small feedings of carbohydrates are the preferred method of treatment. Dietary substitution of medium-...

Digestion of the Various Foods by Hydrolysis

Almost the entire fat portion of the diet consists of triglycerides (neutral fats), which are combinations of three fatty acid molecules condensed with a single glycerol molecule. During condensation, three molecules of water are removed. Digestion of the triglycerides consists of the reverse process the fat-digesting enzymes return three molecules of water to the triglyceride molecule and thereby split the fatty acid molecules away from the glycerol. Here again, the digestive process is one of hydrolysis.

Cardiovascular function

Steroids and vascular risk factors Premenopausal women suffer significantly less from cardiovascular disease than men, and traditionally it has been thought that the relationship between sex steroids and cardiovascular disease is predominantly determined by the relatively beneficial effects of estrogens, and by the relatively detrimental effects of androgens on lipid profiles 101 . Nevertheless, the vast majority of cross-sectional studies in men are not in agreement with this assumption they show a positive correlation between FT levels and HDL cholesterol 111-113 , and a negative correlation, with fibrinogen, plasminogen activator inhibitor-1 105 , and insulin levels as well as with coronary heart disease 115,116 , but not with cardiovascular mortality 117-119 . Low T in men is a component of a plurimetabolic syndrome (syndrome X)-associated increase in abdominal fat, insulin resistance, type 2 diabetes, high blood pressure, hypertriglyceridemia, low HDL cholesterol, and a...

Inherited Low Maximal Oxygen Uptake Cardiovascular Risk Profile and Metabolic Syndrome

A specific aim of our research has been to determine whether rats selected on the basis of low versus high intrinsic exercise performance also differed in VO2max, mitochondrial oxidativepathways, and cardiovascular risk factors linked to the metabolicsyndrome.After eleven generations of selective breeding based upon aerobic treadmill running, contrasting rat lines of Low Capacity Runners (LCR) and High Capacity Runners (HCR) were obtained 66, 67 . HCR were superior to the LCR for distance run to exhaustion (347 ) and VO2max (60 ). LCR demonstrated a cluster of risk factors for cardiovascular disease, i.e., higher levels of factors such as body mass, visceral adiposity, blood pressure, insulin, glucose, free fatty acids, and triglycerides. This risk profile resembles the metabolic syndrome as described in humans 66 thus, the LCR rat model serves as an experimental model for this condition that is not based upon single-gene, chemical, or physical manipulation, but on artificial...

Problems in risk stratification

When there have been many trials conducted in a particular field, it is possible to perform risk stratification at the level of individual trials. This was carried out in the case of cholesterol lowering,17 using the CHD mortality rate in the control arm of the trials as the stratification variable. This stratification is of clinical use, since this is the risk of CHD death of patients without treatment, i.e. the risk level which the clinician would want to use for deciding whether or not patients will benefit from therapeutic cholesterol lowering. The analysis can also be performed using control group CHD mortality risk as a continuous variable, through the

Causal Involvement Of Hsp 60 In Atherogenesis

Evidence for a causal involvement of hsp65 in atherogenesis is provided by our animal models induced by immunization or feeding a cholesterol-rich diet (6). As mentioned earlier in this chapter, we have immunized rabbits one or more times with various antigens, with or without adjuvants. The antigens and adjuvants, respectively, included human and rabbit atherosclerotic lesion proteins, ovalbumin, recombinant mycobacterial hsp 65, Freund's complete and incomplete adjuvants, and two hsp-free adjuvants, Ribi and lipopeptide. Arteriosclerotic lesions in the intima of the aortic arch developed only in animals immunized with antigenic preparations containing hsps, either as whole mycobacteria or purified recombinant hsp 65, irrespective of the addition of any further antigens and despite normal serum cholesterol levels (6,78). These results suggest that an (auto)immune response to hsp 65 may initiate the development of atherosclerosis.

The Influence of Genetic Variations on Drug Effects in Other Diseases

Therapy with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) decrease total and low-density lipoprotein cholesterol and has proven to be effective for cardiovascular risk reduction. However, considerable interindividual variation exits in response to therapy. Several SNPs across many genes known to affect cholesterol synthesis, absorption, and transport and statin metabolism were identified. Some gene variants seem to predict whether patient will benefit from treatment with statins (40).

Exercise in the Treatment of Obesity

Physical exercise is known to be an effective therapy for overweight and obesity 1 in fact, exercise, when combined with dietary advice, enhances weight loss 2 and prevents weight regain 3, 4 . An increase of physical activity, which induces an increase of exercise-induced and resting energy expenditure, can effectively counterbalance the reduction of energy consumption determined by decreased food intake 1 , while preventing the reduction of lean mass associated with weight loss 5 . Furthermore, the increase of activity level determines an improvement of insulin sensitivity, glucose tolerance, lipid profile, and blood pressure, as well as a reduction of several inflammatory markers, leading to a substantial decrease of long-term cardiovascular risk 1,6 . In patients already affected by obesity-associated conditions, such as type 2 diabetes, hypertension, or dyslipidemia, physical activity is associated with an improvement of blood glucose, blood pressure, HDL cholesterol, and...

Observational Studies

An unfortunate patient who has terminal pancreatic cancer with less than one year to live is unlikely to be randomized to a five-year trial assessing the role of cholesterol reduction therapy in reducing the number of heart attacks, even if he has met all other criteria for the trial.

Measurement of serum and liver cholesterol

Serum was prepared by centrifugation at 3,000 rpm for 10 min. Serum cholesterol was measured using an enzymatic method and commercial kits, Autosera CHO-2. HDL cholesterol was measured in the same manner after precipitating out the LDL and VLDL cholesterol with sulfate-Mg2+ 36. LDL plus VLDL cholesterol was calculated by subtracting HDL cholesterol from the total cholesterol. The cholesterol content of the liver was determined enzymaticallyafter extractionwith isopropanol20.

Nicotinic Acid Doses

Of particular interest for this chapter are the amounts of nicotinic acid used to affect substrate utilization during bouts of exercise, to affect plasma free fatty acid (FFA) levels and to affect cholesterol levels. Two investigations demonstrated significant changes in respiratory exchange ratio (RER) with infusion of 1.4 g of nicotinic acid over 4 h of rest and exercise12 and 1.6 g (1 g intravenous and 600 mg orally) of nicotinic acid given in a 2 h period prior to exercise.11 Two other studies reported significant decreases in plasma FFA levels with ingestion of 200 mg of nicotinic acid 10 min prior to testing22 and 3.2 mg kg (235 mg for a 70-kg person) 2 h prior to testing with 1.6 mg kg administered every 30 min thereafter.23 Other exercise studies to report on the amount of nicotinic acid administered were Jenkins16 with 200 mg at the start and 100 mg after 1 h, and Lassers et al.18 with a 200-mg IV bolus and continuous intravenous of 3.8 mg min. Both Heath et al.14,15 studies...

The Difficulty of Effect Modification

As an alternative approach, consider the following cross sectional evaluation. An investigator has obtained demographic and lipid data on 4,159 patients who have sustained a heart attack. He is interested in identifying demographic measures that may be related to LDL cholesterol levels. He will do this using a cross-sectional design.* Before his evaluation begins, the investigator thoroughly reviews the literature and consults with other lipid specialists. His review suggests that each of the main effects of age, gender, race, country, and family history of heart disease are related to LDL cholesterol levels. The investigator also notes that others have suggested that each of smoking history, alcohol consumption, exercise level diabetes, hypertension, and use of beta blockers may exert influence as well, although the evidence for these latter variables is somewhat weaker. The investigator must consider his decision strategy and alpha allocation decisions carefully. He believes a...

Serum cholesterol concentration and risk of ischaemic heart disease

Figure 9.2 Percentage reduction in risk of ischaemic heart disease (and 95 confidence intervals) associated with 0-6 mmol l serum cholesterol reduction in 10 prospective studies of men. Studies referenced by Law et al.14 Figure 9.2 Percentage reduction in risk of ischaemic heart disease (and 95 confidence intervals) associated with 0-6 mmol l serum cholesterol reduction in 10 prospective studies of men. Studies referenced by Law et al.14 regression dilution bias.15 Although all of the 10 studies showed that cholesterol reduction was associated with a reduction in the risk of ischaemic heart disease, they differed substantially in the estimated magnitude of this effect. This is clear from Figure 9.2, and the extreme value that is obtained from an overall test of homogeneity ( 9 127, P 0-001). This shows that simply combining the results of these studies into one overall estimate is misleading an understanding of the reasons for the heterogeneity is necessary. Figure 9.3 Percentage...

Further Research Table

In second-line therapy in patients naive to NNRTIs, it could be interesting to compare delavirdine with efavirenz and or nevirapine, including a specific evaluation of isolates that have increased susceptibility to NNRTIs. It could have a definite advantage and the effort is fully justified. In salvage therapy, delavir-dine could be most useful, because clinicians struggle to design regimens that could produce maximal virological suppression. It could be argued that the additional PI-boosting effect of delavirdine could be clinically significant. A more recent study on the effect of delavirdine on lipid profiles in 10 patients taking delavirdine in combination with nelfinavir showed a 35.2 increase in high-density lipoprotein cholesterol levels during 8 wk (89). It may be that this benefit will be observed when delavirdine is combined with other PIs, further enhancing its attractiveness as a component of salvage therapy.

Physiology Aminostatic Theories

Fallopian tubes, 1011, 1012f estrogen effects on, 1017 inflammation of, 1025 ovum in, 1027,1028-1029,1028f progesterone effects on, 1018 Fallot, tetralogy of, 139, 275-276, 275f Familial hypercholesterolemia, 850 Fanconi's syndrome, 414 Farsightedness, 619, 619f Fastigial nucleus, 701, 701f Fat(s). See also Lipid(s) Triglycerides. brown, 887-888,896 carbohydrate formation from, 838 depletion of, 874-875, 874f deposition of, estrogen and, 1018 digestion of, 811-812,811f, 812f emulsification of, 811 metabolism of. See also at Triglycerides. bile salts and, 804-805 carbohydrate lack and, 846 cortisol and, 846, 952 growth hormone and, 846, 922-923 in diabetes mellitus type I, 973-974 insulin and, 965-966, 969-970 liver in, 842,844, 861-862 regulation of, 846 thyroid hormone and, 846, 936 neutral, 12f, 46f, 294f, 850. See also neuromuscular junction, 88 skeletal muscle, 82 synaptic, 570 Fatty acids, 840. See also Triglycerides. acetyl-CoA conversion to, 844-845, 845f beta-oxidation of,...

Lipid Containing Solubilizing Vehicles in Capsules Three Solubilizing Excipients

Ascending the level of complexity of lipid-based formulations are those that contain mixtures of three excipients. Typical examples of such combinations include 1) medium-chain triglycerides, PEG, and PG 2) TPGS, PEG 400, and PG 3) oleic acid, cremophor EL, and ethanol or PG 4) Polysorbate 20, PEG 400, and povidone 5) medium-chain mono and diglycerides, a-tocopherol, and povidone 6) medium-chain triglycerides, glycol esters of fatty acids, and aspartic acid. There are at least seven commercially available, three-excipient lipid-based oral formulations, and all are delivered in soft gelatin capsules. 1) A mixture of medium-chain triglycerides, polyethyleneglycol, and propylene glycol solubilizes the combination of 250 mg of acetaminophen, 10 mg of dextromethorphan HBr, 100 mg of guaifenesin, and 30 mg of pseudoephedrine HCl in over-the-counter Robitussin Cold, Cough & Flu liquid-filled capsules. the possibility of solubilization through manipulation of the formulation pH. The initial...

Proper Versus Improper Subgroups

Determining subgroup membership at the beginning of the trial requires not only that the subgroup must be defined at the beginning of the study, but also that the subgroup strata membership should be defined prospectively as well. This is a straightforward procedure to apply to the gender subgroup with its two strata. However, for other subgroups of clinical interest, the process can be complex. For example, while it can be relatively straightforward to evaluate the relationship between cholesterol levels subgroup strata 1) less than 175 mg dl, and 2) greater than 175 mg dl and the cumulative incidence of stroke, the evaluation of these strata when they are based in follow-up levels of cholesterol is problematic. The problems arise for two reasons. The first is that patients can change subgroup strata as the study progresses and the their cholesterol levels fluctuate. This makes it difficult to determine definitively and convincingly subgroup membership, and the analysis can suffer...

Insulin Resistance

In recent years, essential hypertension, in conjunction with several other physiological parameters (glucose intolerance, upper-body obesity, elevated triglycerides), has been shown to be related to insulin resistance. The combination of these variables has been called the insulin resistance syndrome or Syndrome X (Reaven, 1988). Insulin resistance is commonly cited as a causal agent for Type II diabetes. In contrast to Type I diabetes, which is characterized by the body's lack of insulin production, normal or even enhanced amounts of insulin are typically available in Type II diabetes the insulin receptors, however, are insensitive to insulin. It is generally thought that insulin resistance represents an adaptive bodily response to prevent additional weight gain that accompanies unhealthy lifestyles and dietary practices. Under conditions of extreme insulin resistance, an overabundance of sugars and lipids remains in the bloodstream rather than being absorbed into body tissue....

Confounding

The fact that randomised controlled trials are included in meta-analyses does not mean that comparisons being made between trials are randomised comparisons. When relating outcomes to characteristics of the trial participants, or to differences in treatments used in the separate trials, or to the situations in which treatments were given, the associations seen are subject to the potential biases of observational studies. Confounding could exist between one trial characteristic - say drug trials versus diet trials in the case of cholesterol lowering - and another characteristic, such as level of risk of the participants in the trial. In many cases there are simply too few trials, or differences in the average characteristics of participants in the trials are too small, to be able to perform a stratified analysis at the level of the individual trial. It may be possible to consider strata within the trials (e.g. male versus female, or those with or without existing disease), to increase...

Acknowledgements

17 Davey Smith G, Song F, Sheldon TA. Cholesterol lowering and mortality the importance of considering initial level of risk. BMJ 1993 306 1367-73. 19 Holme I. Relationship between total mortality and cholesterol reduction as found by meta-regression analysis of randomized cholesterol lowering trials. Contr Clin Trials 1996 17 13-22.

Post Therapy

In terms of cholesterol-lowering medications, the recently revised NCEP recommendations provide a well thought-out minimum of care that should be provided for the screening and treatment of increased risk for coronary artery disease 126 . Medi-astinal radiotherapy should be considered as an independent risk factor in determining whether an individual's lipid profile suggests the need for treatment. A decision to use medication should be made in consultation with a preventive cardiologist, who ideally should follow the patient at least initially. Based on their increased risk, survivors treated with chest and brain irradiation should be screened with a fasting lipid profile soon after completion of their therapy and on a periodic basis throughout their lives. Screening tests for the indirect effects on the cardiovascular system should also be performed periodically - in particular, for pulmonary function and thyroid function.

Efficacy Seduction

However, an examination of the clinical findings raised important questions hidden by a cursory assessment of the p-value. The seven-year cumulative incidence of fatal and nonfatal MI's was 8.6 in the placebo group. In the active group, the cumulative event rate was 7.0. These findings represented a 19 reduction in the fatal nonfatal MI rate associated with cholestyramine. It is useful to ask what this reduction means for the population to be treated. Simply put, in order to prevent one fatal or nonfatal MI, 63 men would have to be treated for seven years. This is a modest treatment effect at best. In addition, the cost of this treatment would be 12,000 per patient. Thus, 756,000 would be spent on 63 patients to pre

Hypolipidemic Agents

The primary developmental mechanism of the atherosclerotic process is not completely understood. It seems likely that the development of atherosclerosis is preceded by metabolic abnormalities of the synthesis, transport, and utilization of lipids. Lipids such as triglycerides and cholesterol esters are circulated in the blood in the form of particles (lipo-proteins) wrapped in hydrophilic membranes that are synthesized from phospholipids and free cholesterol. Cholesterol is transported by particles of various sizes synthesized from triglycerides, cholesterol esters, and phospholipids, each of which plays a very specific role. Thus, chylomicrons are the largest particles with the lowest density, and they are formed in the epithelial cells of the small intestine and are synthesized from exogenic triglycerides (fats) which are used for carrying out transport functions. Very low-density lipoproteins are formed in the liver and include primarily endogenic triglycerides and cholesterol...

LRC Results

As we have seen earlier, LCR studied the role of cholesterol reduction therapies in reducing the risk of clinical events. Designed in the 1970s by lipidolo-gists working in concert with experienced clinical trial methodologists, the LRC trial set out to establish with some finality the importance of cholesterol level reduction in reducing the clinical sequelae of atherosclerotic cardiovascular disease. It was designed to randomize patients either to cholesterol reduction therapy or to no therapy, and then to follow these patients over time, counting the number of fatal and nonfatal myocardial infarctions that occurred. LRC required over 3,500 patients to be followed for seven years to reach its conclusion, incorporated into a pre-specified hypothesis test. The final trial test statistic would be assessed using a pro-spectively declared one-sided hypothesis test at the 0.01 level. If the resulting z-score at the trial's conclusion was greater than 2.33, the investigators would conclude...

Conclusions

There is a wide selection of solubilizing excipients that can be used in oral formulations either by themselves or in combination with other excipients. The sol-ubilizing excipients are generally categorized into various types including water-soluble organic solvent excipients, water-insoluble organic solvents excipients, triglycerides, surfactants, phospholipids, and cyclodextrins. The water-soluble organic solvents in commercially available solubilized oral formulations are ethanol, glycerin, polyethylene glycol 300 (PEG 300), PEG 400, propylene glycol, and Transcutol HP. The non-ionic surfactants in commercially available solubilized oral formulations include polyoxyl 35 castor oil (cremophor EL), polyoxyl 40 hydrogenated castor oil (cremophor RH 40), polysorbate 20, polysorbate 80, d- -tocopherol polyethylene glycol 1000 succinate (TPGS), sor-bitan monooleate, polyoxyl 40 stearate, and various polyglycolyzed glycerides including Labrafil M-1944CS, Labrafil M-2125CS, Labrasol ,...

Diagnosis

Response rates to specific treatment with oral metronidazole or vancomycin are typically better than 95 and these drugs constitute the most widely used therapies for C. difficile diarrhea.49 It should be remembered that this disease is invariably precipitated by antimicrobial therapy and eventual recovery for some patients likely involves the re-establishment of a protective colonic bacterial flora after discontinuation of all antimicrobials. Up to 23 of patients may respond to simple withdrawal of the offending antimicrobial and this strategy should be considered for patients with mild symptoms.32 Specific therapy should be administered orally and continued for 10 days. Antiperistaltic agents, such as phenoxylate-atrophine (Lomotil) should be avoided as these drugs may predispose patients to toxic megacolon when used alone.49 Vancomycin was the first effective therapy for C. difficile diarrhea and fecal drug concentrations several log10 higher than the minimum inhibitory...

Beyond Trial Results

Clinical trials are often constrained in terms of the length of follow-up for clinical and resource consequences. Many trials of therapeutic interventions measure short-term mortality. In many situations the economic analyst will wish to extrapolate data beyond the period observed in the clinical trial. Also, the economic analyst who wishes to link the intermediate biologic endpoint of a clinical trial to final health outcomes such as mortality reduction and life expectancy needs to rely on modeling. This is because more general measures, such as life-years saved, are more relevant to economic evaluation than short-term measures such as percentage of LDL cholesterol reduction at six months.

Battling the Bloat

Soluble fiber lowers the bad cholesterol, or low-density lipoproteins (LDL), in your body. Experts aren't entirely sure how soluble fiber works its magic, but one popular theory is that it gets mixed into the bile the liver secretes and forms a type of gel that traps the building blocks of cholesterol, thus lowering your LDL levels. It's akin to a spider web trapping smaller insects. Insoluble fiber doesn't affect your cholesterol levels at all, but it regulates your bowel movements. How does it do this As the insoluble fiber moves through your digestive tract, it absorbs water like a sponge and helps to form your waste into a solid form faster, making the stools larger, softer, and easier to pass. Without insoluble fiber, your solid waste just gets pushed down to the colon or lower intestine, where it is stored and dried out until you're ready to have a bowel movement. High-starch foods are associated with drier stools. This is exacerbated when you ignore the urge, as the colon will...

Lipid Metabolism

Several chemical compounds in food and in the body are classified as lipids. They include (1) neutral fat, also known as triglycerides (2) phospholipids (3) cholesterol and (4) a few others of less importance. Chemically, the basic lipid moiety of the triglycerides and the phospholipids is fatty acids, which are simply long-chain hydrocarbon organic acids. A typical fatty acid, palmitic acid, is the following CH3(CH2)14COOH. Although cholesterol does not contain fatty acid, its sterol nucleus is synthesized from portions of fatty acid molecules, thus giving it many of the physical and chemical properties of other lipid substances. The triglycerides are used in the body mainly to provide energy for the different metabolic processes, a function they share almost equally with the carbohydrates. However, some lipids, especially cholesterol, the phospholipids, and small amounts of triglycerides, are used to form the membranes of all cells of the body and to perform other cellular...

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