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The 2 Week Diet

The 2-week diet promises to help you shed as much as 19 pounds of body fat in just 14 days (2 weeks). In addition to this, the diet also promises to help you tone up your muscles, decrease cellulite, and improve energy levels. Once you have started the 2 Week Diet, your body responds quickly, and the pounds will start to drop off. With the 2 Week Diet, you will lose weight, but you will do it in a way that is healthy, and that will last after the weight is gone. So many people know the frustrating cycle of losing a few pounds and gaining it right back. The 2-week diet is well written, easy to follow and very informative. You will like the calculations for calorie consumption to lose weight and also how to maintain your body to your satisfaction.This productGuarantee for weight loss. Read more...

The 2 Week Diet Summary

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This is one of the best ebooks I have read on this field. The writing style was simple and engaging. Content included was worth reading spending my precious time.

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Box 12 Microbiomes Contribute to Obesity and Pain

Although human digestive tracts contain many different types of bacteria, more than 90 of the total is composed of two general types the Bacteroidetes and the Fermicutes. These bacteria, along with others, extract energy from foods that would otherwise be indigestible. Obese persons have a higher percentage of Fermicutes in their guts than thin persons, and when obese persons lose weight, the percentage of Bacteroidetes increases. The increased fraction of Bacteriodetes appears to be associated with lower harvest of energy from food.11 A similar difference is observed with genetically obese mice. The obese mice appear to be better able to extract energy from their food, leaving considerably less energy in their feces. When normal, germ-free mice received gut bacteria from obese mice, they put on substantially more body fat than when given bacteria from normal mice, even though food consumption was the same in the two groups. Could gut bacteria contribute to human obesity Could a shift...

Maintaining a Healthy Weight

Being overweight is a major health problem in the United States, and there are many good reasons to keep your weight within a healthy range. You will feel better, look better, and have more energy than men who are overweight. Having more energy makes you more likely to exercise, which can help you fall asleep faster and sleep more restfully. But the most important reason to keep your weight within a healthy range is that you will lower your risk for certain chronic diseases, including heart disease, high blood pressure, diabetes, and certain forms of cancer. Doctors no longer believe that it is acceptable to gain a few pounds as you age. Maintaining your weight at a reasonable level throughout your life is key when it comes to reducing your risk for disease. Many overweight men have difficulty reaching their healthy body weight, and the more you weigh above your ideal weight, the harder it can be to lose the extra pounds. It is encouraging to learn, then, that losing even a relatively...

The Mediterranean Diet and Risk of CVD

In view of the numerous cultures and agricultural patterns of the Mediterranean region, the 'Mediterranean' diet cannot be characterized by a specific nutrient profile rather, this term is applied to a dietary pattern. In this context, the dietary pattern, extensively described in the Seven Countries Study remains a historical reference point (Table 2.1). This study, which began in the mid-1950s, was the first to systematically examine the relationship between diet and risk of CVD across geographically and culturally distinct populations. The countries were the United States, Finland, The Netherlands, Italy, Yugoslavia, Greece, and Japan. Over the course of 5years of follow-up, CHD mortality varied widely among these countries with the highest average annual age-adjusted incidence occurring in Finland (47 10,000) and the US (47 10,000), and the lowest in Greece (8 10,000), Japan (9 10,000), and Italy (7 10,000).12 Results suggest that consumption of a Mediterranean diet, similar to...

Clinical Trial Results Variations to the Mediterranean Diet

The interpretations of the findings from these and other observational studies suggest that partial adoption of the Mediterranean diet is associated with reductions in CVD across many populations, in the young and old, and those with and without prevalent disease ages. Since observational studies do not establish a cause and effect relationship, a stronger test of the hypothesis for a relationship between the effects of the Mediterranean diet on CVD risk is in the setting of a clinical trial. Two trials designed to test the effects of variations of the Mediterranean diet on clinical CVD outcomes were the Lyon Diet Heart Study8 and the Indo-Mediterranean Diet Heart Study.25 Both randomized trials were conducted in participants with established CVD.

Indo Mediterranean Diet Heart Study

A recently completed trial conducted in India, the Indo-Mediterranean Diet Heart Study,25 complements findings from the Lyon Diet Heart Study. The study population consisted primarily of men ( 90 ) who were at high-risk for either a first myocardial infarction or a recurrence approximately 60 had a history of myocardial infarction at baseline, and 35 had a recent (< 4 weeks) myocardial infarction. In contrast to the Lyon Diet Heart Study, two-thirds of participants were vegetarian at baseline. All participants were given advice to reduce their intake of fat, saturated fat, and cholesterol (< 30 kcal from fat, < 10 kcal from saturated fat, and < 300 mg cholesterol day). Those participants in the intervention arm were also advised to increase their consumption of fruits, vegetables, and nuts and to use mustard seed and soybean oil (3-4 servings day), both of which are rich in ALA. It is noteworthy that approximately 60 of calories came from carbohydrates, of which a substantial...

Mediterranean Diet Effects on Oxidative Stress

The direct relationship between traditional CVD risk factors and risk of atherosclerosis is well established. Dietary modifications which lower blood pressure and lipids provide a likely explanation for much of the risk reduction. However, oxidative stress, including oxidation of LDL-c (oxLDL) appears to be an important, Oxidative stress markers commonly used, including nonspecific in vitro assays to determine the susceptibility of lipids to oxidation (i.e. lag time, thiobarbituric acid substances, malondialdehyde, oxygen radical absorbing capacity (ORAC) or assays that measure, in vivo, end-product of oxidative damage to lipids (e.g., breath ethane or urinary isoprostanes). Formation of these oxidation products is dependant on free radical activity (i.e. metabolic rate), substrate concentration (i.e. lipids), and antioxidant activity (both endogenous and dietary). Hence, alterations in dietary patterns can give important insight into the benefit or harm of nutrients when linked to...

Role of obesity and body fat distribution in cardiometabolic risk

Obesity can be simply defined as an excessive amount of body fat which increases the risk of medical illness and premature death. For clinical purposes, assessments that are routinely used to define obesity include body weight and body mass index (BMI)1. The BMI assessment represents the relationship between weight and height, and is derived by calculating either the weight (in kg) divided by the height (in meters squared), or the weight (in pounds) multiplied by 704 divided by the height in inches squared1. Using the BMI as the main criteria, classification of obesity into risk categories have been proposed (Table 3.1). The BMI classification is based on data that has been collected from large epidemiological studies that evaluated body weight and mortality2-4. This classification provides clinicians with a mechanism for identifying patients at high risk for complications associated with obesity. It has been well established that those individuals considered obese, i.e. BMI a 30, are...

Describe the preoperative management of a morbidly obese patient with a difficult airway Assume that the patient is

A morbidly obese patient is considered at increased risk of pulmonary aspiration during induction of anesthesia because of delayed gastric emptying and the possibility of difficult airway management. Therefore H2 blockers given the evening before (if possible) and the morning of surgery, preoperative metoclopramide, and oral nonparticulate antacids are in order. Glycopyrrolate is useful for planned fiberoptic intubation. It improves visualization by drying secretions, increases the effectiveness of the topical anesthesia, and decreases airway responsiveness. Opioids and benzodiazepines should be judiciously titrated, using supplemental oxygen and close observation to ensure an awake, appropriately responding patient who can protect his or her own airway.

Macrophages contribute to obesityinduced adipose tissue inflammation

Studies of obesity-induced inflammation have until recently focused on the effects of specific inflammatory molecules on metabolically important cell types, including hepa-tocytes, adipocytes, myocytes, and hypothalamic neurons (23,82-84). Several recent analyses of adipocyte and nonadipocyte cell populations within adipose tissue demonstrate that much of adipose tissue inflammatory gene expression is derived from the nonadipocyte, stromal vascular cells (85-87). In the original model proposed by Hotamisligil and Speigelman, obesity-induced increases in lipid content of adipocytes activate an inflammatory pathway in adipocytes. In this model, resulting proinflamma-tory cytokines act in autocrine fashion to impair adipocyte metabolic function, in a paracrine fashion to alter preadipocyte differentiation, and systemically to reduce insulin sensitivity. The role of classic inflammatory and immune cells has not been clearly delineated in adipose tissue physiology or obesity-associated...

Obesity epidemic in the united states

Prevalence rates for overweight and obesity in the United States are generated from the National Health and Nutrition Examination Survey (NHANES) program. These cross-sectional surveys have been conducted since 1960 on a large representative sample of the US population and provide national estimates for overweight and obesity in children and adults from 2 to 74 yr of age. The National Health Examination Survey (NHES I, Fig. 1. J-shaped curve of all-cause mortality compared with body mass index. From ref. 1. Table 1 Classification of Overweight and Obesity by BMI Fig. 1. J-shaped curve of all-cause mortality compared with body mass index. From ref. 1. Table 1 Classification of Overweight and Obesity by BMI Obesity class Obesity Data for these surveys reveal dramatic increases in overweight or obesity between NHANES II and III, which were continued at an even greater rate in 1999-2000. The prevalence of overweight increased significantly, from 56 in NHANES III to 65.2 in 1999-2000....

Ethnicityrace and obesity

Obesity and extreme obesity prevalence increased in all sex and racial ethnic groups between NHNAES III and 1999-2000. Differences in obesity rates by ethnicity race were found to vary by gender (12). Specifically, no difference in obesity rates were found among African American, Hispanic, or Caucasian men however, among women, African Americans had a higher prevalence of overweight and obesity (77 and 50 , respectively) than Caucasians (57 and 30 , respectively), and Mexican American women had a prevalence that was intermediate between these two (72 overweight and 40 obese). Significant increases in extreme obesity occurred between NHANES III and 1999-2000 in all men and women and for non-Hispanic black women, with similar trends in all other groups (Table 4). Interestingly, although there has been a significant increase in the prevalence of obesity in the past 15 yr, the mean BMI measurements have changed much less. Between NHANES III and 1999-2002 the mean BMI increased 1.7 and 2.5...

Obesity and socioeconomic status

Obesity has frequently been reported in the past to occur disproportionately among economically disadvantaged populations in the United States (15-17) however, more recently, substantial variation in obesity rates between income and ethnic groups over time have emerged (14,18). Using level of education attainment to categorize socioeconomic status (SES), Zhang and Wang found a gradual decrease in the association between SES (determined according to level of education) and obesity between 1971 and 2000, particularly among women, and a disproportionate increase in the obesity prevalence in the high-SES groups (18) (Fig. 3). Fig. 3. Secular trends in the association between SES and obesity among US adults, 1971-2000. With permission from ref. 18. Fig. 3. Secular trends in the association between SES and obesity among US adults, 1971-2000. With permission from ref. 18. Chang and Lauderdale (14) compared obesity rates in non-Hispanic blacks, whites, and Mexican Americans by income using...

Understanding obesity requires a developmental and evolutionary perspective

Ever since Neel's proposition of the thrifty gene hypothesis more than 40 yr ago (1), evolutionary explanations for the origins of human obesity have assumed that our tendency to put on weight in a modern environment is the vestige of a trait that was beneficial under the more austere nutritional conditions of the past. Neel proposed that, for millions of years during the Paleolithic, humans and our hominin ancestors survived as roaming bands of foragers who faced an unpredictable food supply. Given this, an ability to capitalize on any excess energy by efficiently depositing it as fat during periods of feast would have boosted the chances of surviving the inevitable future famine. We inherited our genes from ancestors who survived these recurrent ecological crises, which now leave us prone to obesity and diabetes in a contemporary environment of nutritional abundance. Neel's hypothesis was invaluable for stimulating interest in the evolutionary origins of human obesity. In...

Developmental pathways to obesity

Given that infant and child mortality is highest as a result of developmentally mediated undernutrition during the earliest stages of the lifecycle, natural selection operating at this age may have had an important influence on the evolution of human metabolism. It is notable, for instance, that the challenge of surviving recurrent infections shares similarities with Neel's vision of a feast-famine scenario, and might be expected to favor the rise of similar metabolic-disease predisposing genes. In this sense, early life might be likened to an ontogenetic bottleneck through which any adult metabolic traits must first pass (17). Although all humans experience this age of heightened energetic vulnerability, there is much variation in the environments that individuals experience, which determines whether they will be forced to rely on such contingencies as brain sparing, lipolysis, or rapid replenishment of body fat. There is now considerable experimental evidence that one's early...

Prevalence ofObesity Too Low During Periods Between Famines to Be a Strongly Selected Trait

Although hunting-gathering has largely died out as a lifestyle, there are still many tribal communities in the third world subsisting on agriculture, using practices effectively unchanged for thousands of years. If the model in Fig. 1 is realistic, all the individuals in these populations should carry thrifty genes conferring efficient fat storage capabilities. Table 1 summarizes some estimates of body mass index (BMI) in hunting-gathering and subsistence-farming populations. Only one of the papers from which these measurements are taken indicates that during the collection of the anthropological measurements the communities were under any form of food restriction resembling a famine. Yet, despite being in generally nonfamine conditions, the individuals are universally characterized by being in the BMI range from 17.5 to 21.0 at the very lean end of normal. None of the communities even approaches the cutoff point for being overweight, never mind being obese. In the one study in which...

Obesity Therapeutics Prospects and Perspectives

Introduction - The prevalence of obesity is rising at an alarming rate. When measured by Body Mass Index (BMI weight in kilograms divided by the square of height in meters), a BMI of 30 is the threshold for obesity. In the United States alone, an analysis of the National Health and Nutrition Examination Survey (NHANES IV) data from 1999-2000 found that the age-adjusted prevalence of obesity was 30.5 and had increased by approximately 8 in just 5 years (NHANES III 1988-1994) (1). This shocking increase in obesity has been mirrored to varying degrees throughout the world. Obesity is often mischaracterized as a cosmetic, or life style issue when in fact it is a devastating disease with tremendous health and financial consequences. In the US alone, it has been estimated that there are greater than 300,000 deaths per year (2). This distressing effect on life expectancy is largely related directly to the life threatening co-morbidities of obesity such as non-insulin-dependent diabetes,...

Current Approaches To Obesity Therapeutics

On-going clinical trials While there are currently a large number of clinical trials reported to be on-going for the treatment of obesity, this review will focus on three that have garnered the most attention recently SR-141716A (Rimonabant), P-57, and recombinant human ciliary neurotrophic factor (rCNTF, Axokine) (11).

The Untapped Potential Of Antiobesity Drugs

The large potential market and the shortage of safe, efficacious compounds is driving many researchers to undertake the difficult task of creating new anti-obesity drugs. Overall the track record of the pharmaceutical industry has been poor in this area, but the recent explosion in our understanding of the biology of obesity has changed the drug discovery landscape. The identification of a multitude of new targets for obesity therapeutics, and a deeper understanding of existing targets, has increased our potential for finding the right focus for increasing efficacy. And while there is a higher sensitivity for safety in anti-obesity therapeutics then that for cancer therapeutics, there is also a greater understanding of the health and financial consequences of this unmet medical need. While the potential of anti-obesity drugs currently remains largely untapped, the industry should be optimistic about the finding solutions to these dual issues In the future. 4. D. Thompson and A.M....

Obesity and sleep apnea

Obesity is defined using the body mass index (BMI) (Table 51-1). TABLE 51-1. DEFINITION OF OBESITY TABLE 51-1. DEFINITION OF OBESITY Class I obesity Class II obesity Morbid obesity BMI, Body mass index. BMI, Body mass index. 2. Discuss the cardiovascular considerations in the obese patient. Systemic hypertension, pulmonary hypertension, left and right heart failure, and coronary artery disease are all more common in the obese patient. As body mass increases, so does oxygen consumption. Cardiac output, stroke volume, and circulating blood volume increase to meet increased demand. Systemic hypertension in time results in left ventricular hypertrophy. Coronary artery disease, combined with the increased likelihood of diabetes mellitus in the obese, increases the risk for silent myocardial infarction. 3. Review some pulmonary and respiratory considerations in the obese patient. Obesity is typically associated with hypoxemia, the mechanisms of which include 4. What are the...

Key Points Obesity And Sleep Apneay

Morbidly obese patients have numerous systemic disorders and physiologic challenges, including restrictive lung disease, obstructive sleep apnea, coronary artery disease, diabetes, hypertension, cardiomegaly, pulmonary hypertension, and delayed gastric emptying. Safe anesthetic practice requires preparation for diagnosis, monitoring, and emergent treatment of any of these conditions. 2. Obese patients may be difficult to ventilate and intubate, and they may desaturate quickly after anesthetic induction. Backup strategies should always be considered and readily available before airway management begins. 4. Obese patients often have OSA, requiring appropriate diagnosis and care, especially in the postoperative period. The Obesity Society http www.obesity.org 2. Brodsky JB, Lemmens HJ Regional anesthesia and obesity. Obes Surg 17 1146-1149, 2007. 5. Haque AK, Gadre S, Taylor J, et al Pulmonary and cardiovascular complications of obesity an autopsy study of 76 obese subjects. Arch Pathol...

Obesity And Abdominal Adiposity

The problem of obesity has reached epidemic proportions in the majority of developed nations worldwide. The World Health Organization (WHO) has reported that over 1 billion adults worldwide meet the definition for overweight (body mass index (BMI) of greater than 25 kg m2) and at least 300 million adults meet criteria for clinical obesity (BMI of greater than 30 kg m2)17. Obesity is associated with a myriad of medical conditions including coronary artery disease, peripheral arterial disease, cerebrovascular disease, congestive heart failure, the metabolic syndrome, hypertension, insulin resistance, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, liver disease, and degenerative joint disease. A subset of obese patients demonstrate abdominal obesity or adiposity which is defined by increasing waist circumference, sagittal abdominal diameter, and waist-to-hip ratio. Waist circumference and sagittal abdominal diameter have been shown to correlate best with intra-abdominal...

The Influence of Dietary Fats on Blood Cholesterol Levels and Distribution of Fatty Acids

Blood cholesterol levels and risk of cardiovascular disease are influenced by dietary intakes of fats. The intake of red meats and saturated fats are a primary cause of elevated blood cholesterol levels.25 Monounsaturated fats generally have a neutral effect on cholesterol, whereas polyunsaturated fats decrease cholesterol levels.26 Dietary cholesterol can increase blood cholesterol levels, but contributes less to blood cholesterol levels than saturated fats.13 Specific fatty acids within each major class, saturated, monounsaturated, and polyunsaturated, often have unique effects on blood cholesterol levels and should be considered on an individual basis. Palmitic acid, a 16-carbon saturated fatty acid, is a major contributor of saturated fat intake in the United States diet, accounting for greater than 60 of the saturated fat intake. It is associated with an elevation in LDL levels27 and may cause these elevated levels by inhibiting the expression of LDL receptors on cell surfaces.28...

Obesity as an inflammatory condition

Obesity produces a state of low-grade inflammation, characterized by elevated circulating concentrations of acute-phase proteins, such as C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen (9,10). CRP is elevated moderately in obese men and highly in obese women (11). Hak et al. reported that in a group of healthy middle-aged women, CRP was approximately threefold higher in the group whose body mass index (BMI) was in the upper half (9). The mean CRP concentration in the upper-BMI group was 1.15 mg L, around the threshold of a clinically elevated level (11). There are at least two theories as to why obesity should cause a state of inflammation. First, the growth especially the rapid growth of adipose tissue may cause local hypoxia due to inadequate perfusion and result in the generation of angiogenesis factors such as vascular endothelial growth factor (VEGF) and 11 -hydroxysteroid dehydro-genase type 1. Overexpression of the latter enzyme in rodents has...

Role of leptin resistance in obesity and insulin resistance

Receptors in the hypothalamus decreases food intake and increases energy expenditure via uncoupling proteins (UCPs) in fat and muscle. UCPs are mitochondrial proteins that allow for oxidation of substrates with the production of heat, rather than storage of energy in the form of ATP. Thus leptin serves as part of an adipostat mechanism, whereby increased adiposity sets in motion responses that will eventually reduce adiposity. In 1994, Friedman et al. discovered that ob ob mice are leptin-deficient and lose weight following leptin treatment (15). However, obese humans are typically leptin-resistant and have higher-than-normal circulating concentrations of leptin. Leptin resistance in humans has two components impaired transport of leptin across the blood-brain barrier and impaired signaling via hypothalamic leptin receptors (16). In addition to its function as a direct regulator of adiposity, leptin is also an insulin-sensitizing hormone (17,18). Thus, the reduced responsiveness to...

Role of tnfa in linking obesity to insulin resistance

We hypothesize that locally produced TNF-a may contribute to insulin resistance in one of two ways. First, obesity may cause insulin resistance in by increasing TNF-a expression in targets such as muscle. Support for this concept is our report that diet-induced obesity in rats is accompanied by reduced insulin-stimulated glucose transport in skeletal muscle, together with an increase in muscle expression of TNF-a (34). Alternatively, obesity may increase TNF-a expression in adipose tissue, leading to the release into the circulation of other cytokines that are capable of causing systemic insulin resistance.

Assessment of overweight and obesity in epidemiological studies of disease

Definitions for classifying and reporting healthy weight, overweight, and obesity in populations have historically been based on measures of weight and height rather than clinical measures of adiposity (5,6). Although weight is the simplest anthropometric index of excess body fat, it does not distinguish between lean body mass (comprised primarily of muscle, bone, and extracellular water) and adipose tissue (5). Thus, measures of weight adjusted for height provide a better approximation of the proportion or total amount of adipose tissue in the body than does weight alone. Since the 1980s, indices of weight adjusted for height have gained favor because they provide a single estimate of adiposity regardless of height and can be easily compared across studies and across populations. By far the most widely used weight-for-height measure is the body mass index (BMI, also called Quetelet's index), which is defined as weight (in kilograms) divided by height (in meters squared) (5). The...

Overweight obesity and cancer mortality

Summary of mortality from cancer according to body mass index for US women in the Cancer Prevention Study II, 1982 through 1998. For each relative risk, the comparison was between women in the highest BMI category (indicated in parentheses) and women in the reference category (BMI 18.5 to 24.9). Asterisks indicate relative risks for women who never smoked. Results of the linear test for trend were significant (p < 0.05) for all cancer sites. Reproduced with permission from ref. 3. Fig. 2. Summary of mortality from cancer according to body mass index for US women in the Cancer Prevention Study II, 1982 through 1998. For each relative risk, the comparison was between women in the highest BMI category (indicated in parentheses) and women in the reference category (BMI 18.5 to 24.9). Asterisks indicate relative risks for women who never smoked. Results of the linear test for trend were significant (p < 0.05) for all cancer sites. Reproduced with permission from ref. 3.

Impact of Obesity on Metabolism

For many years, adipose tissue was considered a passive storage organ, but it is now clear that adipose tissue plays an active role in controlling energy balance. The metabolic alterations of adipose tissue that occur in obesity are numerous. These include an increased release of secretory molecules such as fatty acids, hormones, and proinflam-matory cytokines. Relative decreases in insulin receptor number and function lead to reduced insulin sensitivity, a condition that may contribute to altered fuel partitioning. It has been hypothesized that the insulin resistance associated with obesity may in fact be a protective adaptive mechanism against further weight gain (17). Adipose tissue produces metabolically active proinflammatory molecules called adipocytokines such as tumour necrosis factor (TNF)-a, interleukins (IL), leptin, adiponectin (18-20), and some newly identified molecules such as visfatin (21) and omentin (22). The cytokines within adipose tissue originate predominantly...

Impact of Obesity on Cardiovascular Structure and Function

Obesity is associated with abnormalities in cardiac structure and function (37-39), which can often be alleviated by weight loss (see Table 1). As there is an increased energy requirement to move excess body weight at any given level of activity, the cardiac workload is greater for obese subjects than for nonobese individuals (39). Thus, obese subjects are known to have higher cardiac output (CO) and a lower total peripheral resistance in the absence of hypertension (23). The high CO is attributable to increased stroke volume, whereas heart rate (HR) is usually unchanged (24). The increase in blood volume and CO in obesity is in proportion to the amount of excess body weight (40). Recent evidence from the HyperGen study shows that both increased total fat mass and fat-free mass are able to cause these physiological changes although centrally located adipose tissue is particularly strongly associated with increased CO (41). In moderate to severe cases of obesity, an increased CO may...

CVD Risk Associated With Obesity

The association between overweight obesity and CVD risk has been known for many years with evidence from several large cohort studies (74-76). After 44 yr of follow-up of the Framingham Heart Study, Wilson et al. (77) showed that CVD risk (including angina, myocardial infarction, CHD, or stroke) was higher among overweight men (RR 1.24 95 CI 1.07-1.44), obese men (RR 1.38 95 CI 1.12-1.69), and obese women (RR 1.38 95 CI 1.14-1.68) after adjustment for age, smoking, high blood pressure, high cholesterol, and diabetes. During a 14-yr follow-up of 1 million adults in the United States, it was found that as BMI increased there was an increase in the risk of death from all causes, CVD, cancer, or other diseases for both men and women in all age groups (78). These findings confirmed the previous report of the Nurses' Health Study (79). In the Nurses' Health Study, weight gain of 5 to 8 kg increased CHD risk (nonfatal myocardial infarction and CHD death) by 25 , and weight gain of > 20 kg...

Definition of obesity

A number of methods have been proposed to describe increases in body weight. The most widely used measurement is the BMI, calculated as weight height2 (kg m2). Among adult subjects overweight is defined as a BMI of 25 to 29.9 kg m2, and obesity as a BMI of at least 30 kg m2. Different ethnicities, such as Caucasians and Chinese, have highly contrasting distributions of body weight and height. Males and females differ in their BMI distribution. Age is an obvious modifier of body weight and height. Therefore, age- and sex-specific definitions for different ethnic groups must be applied when comparing effects in various study populations. Growth charts from the Centers for Disease Control and Prevention (CDC) include age- and sex-specific BMI reference values for children and adolescents aged 2 to 20 yr (8). However, BMI does not account for body frame and proportion of muscle mass. This limitation is particularly relevant in pediatric studies because of the effects of maturation and...

Mechanism Linking Obesity and PCOS

The mechanisms linking obesity and PCOS are unclear but may be related to insulin resistance and hyperandrogenism, both of which are commonly documented in lean and obese women with this condition. Insulin resistance is a common but not universal feature of PCOS, although women with insulin resistance appear to be more clinically affected (2). Because insulin resistance is strongly influenced by obesity in non-PCOS subjects, it was initially debated whether insulin resistance and hyperinsulinemia are a primary metabolic disturbance of PCOS or a symptom of the obesity commonly observed in PCOS. Hyperandrogenemia and insulin resistance appear to be independent features of PCOS, with hyperinsulinemia enhancing the expression of hyperandrogenemia by increasing bioavailability of androgens (4) (Fig. 1). Obese women with PCOS show decreased insulin sensitivity and hyperinsulinemia to an extent greater than can be explained by obesity alone (4,5). A synergistic interaction appears to exist...

Obesity and joint structure

Although OA manifests as joint changes that primarily include progressive cartilage loss and bony abnormalities such as subchondral sclerosis, osteophytes, and bone cysts, it is unclear how obesity influences joint morphology. To date, the majority of studies have measured the BMI (kg m2) as an indicator of obesity, and only relatively recently have parameters of body composition, such as fat distribution and lean body mass, been examined in the context of joint disease. Nevertheless, there still remains a paucity of data examining the association between joint structure and increased body mass. This lack of specific data may be partly attributable to the difficulty in obtaining reliable, valid, and sensitive measures of cartilage, bone, and body composition properties non-invasively in human subjects. However, magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DEXA) are becoming widely accepted as noninvasive, reliable, valid, and sensitive measures of cartilage...

Association Between Obesity and Cartilage Properties

Few studies have directly examined the association between obesity and cartilage properties. Radiographic joint space width (JSW) had previously been used as an indirect measure of articular cartilage volume. A study demonstrated that the medial and lateral knee JSW was narrower in obese patients (BMI > 30) compared with nonobese patients (9). This may suggest that obesity is associated with a reduction in the amount of cartilage. However, confounding factors such as varus malignment at the knee, which strongly mediates the association between obesity and medial tibiofemoral JSW (10), were not adjusted for in this study, which challenges the generalizability of the association between obesity and JSW. Indeed, other previous work had failed to demonstrate that obesity was a risk factor for joint space narrowing (JSN) (11). Moreover, the assumption that JSW is a surrogate marker of articular cartilage is often misleading, as the radiographic joint space is composed of structures other...

Association Between Obesity and Bony Properties 221 Bone Mineral Density and Content and BMI

The literature examining the association between obesity and bony properties has predominantly focused on bone mineral density (BMD) and bone mineral content (BMC). Compared with normal-weight people, overweight individuals (BMI > 26) have higher BMD and BMC at both weight-bearing (e.g., femur) and non-weight-bearing (e.g., radius) sites (30). Nevertheless, the association between obesity, defined as an increased BMI, and BMD BMC is not this simplistic and is dependent on several other factors, including body composition. Abdominal obesity, body weight, and muscle strength have emerged as strong correlates of BMD in older persons (31). Although certain parameters of body composition, such as abdominal obesity, are strongly associated with BMD, gender is arguably the strongest factor that mediates the obesity-BMD relationship. In both men and women, decreased BMD occurs after the age of 50 (32), although women demonstrate greater variability than men. In particular, lean body mass...

Association between obesity and oa at different joints

OA is characterized by the degeneration of hyaline articular cartilage and the formation of new bone at synovial joints. The condition most notably affects weight-bearing sites, although non-weight-bearing joints, such as those in the hand, are commonly affected. Although obesity, defined by a larger than normal BMI, is associated with OA at both weight-bearing and non-weight-bearing joints, the strength and consistency of this relationship vary between different anatomical locations. Additionally, little is known about the parameters of body composition, such as fat distribution, and the prevalence of OA at different joints.

Association Between Obesity and Knee OA

The association between obesity and OA is arguably strongest and most consistent at the knee joint. In 1958, Kellgren and Lawrence found that knee OA was more common in obese people, particularly women. Since then, cross-sectional studies have consistently shown an association between obesity and knee OA, which has been stronger for women than men. Among obese middle-aged females with knee OA, it has been reported that the proportion of the disease attributable to obesity is approx 63 (26). Longitudinal studies have consistently demonstrated an association between obesity and knee OA. A 35-yr follow-up study demonstrated a strong association between being overweight and the development of OA, particularly in women (27). Likewise, an increased BMI at a young age was a risk factor for knee OA in males (39). Twin studies have also demonstrated that a twin with tibiofemoral and patellofemoral OA is likely to be 3 to 5 kg heavier than the co-twin. Moreover, twin studies have also...

Association Between Obesity and Hand OA

The evidence examining the association between obesity and hand OA is conflicting. Data from the National Health Examination Survey demonstrated an association between BMI and the presence of hand OA in men after adjustment for age, race, and skin fold thickening (28). However, this relationship was not significant after adjustment for waist girth and seat breadth. A case-control study found that obesity and hand OA were associated (41). Longitudinal data also confirmed an association between radiographic hand OA and BMI in men (42), although the New Haven Survey demonstrated that finger OA and obesity were more strongly associated in women than in men (43). In the Chingford study, obesity was only moderately associated with distal interpha-langeal and carpometacarpal OA, but not with proximal interphalyngeal OA in women (26). Another study found that there was no significant difference in weight within twin pairs discordant for osteophytes at the distal and the proximal...

Association Between Obesity and Hip OA

Similar to the hand, the association between obesity and hip OA is equivocal. A case-control study that examined BMI at 10-yr intervals in men who had received a hip prosthesis because of OA demonstrated that a BMI greater than one standard deviation above the mean was associated with the development of severe OA (45). Relative Data from the First National Health and Nutrition Examination Survey (NHANES-I) failed to demonstrate an association between obesity and hip OA (47). Additionally, parameters of body composition, such as fat distribution, were not associated with hip OA. No association was demonstrated between BMI in the three decades prior to the onset of hip OA (39). Given these contrasting results, no definitive conclusions can be drawn from the available data examining the possible association between obesity and hip OA. To date, the data indicate that at best, obesity is only weakly associated with OA of the hip.

Obesity as Risk for Onset of OA

Longitudinal studies have shown that obesity is a powerful risk factor for the development of knee OA, with one twin study finding a 9 to 13 increased risk for the onset of the disease with every kilogram increase in body weight (35). For every kilogram increase in body weight, a twin had an increased likelihood of developing features of OA at the tibiofemoral, patellofemoral, and carpometacarpal joints. In women with established unilateral knee OA, obesity was the most important factor for the development of OA in the contralateral knee (48). This was based on the finding that 47 of women in the top BMI tertile developed contralateral knee OA, whereas only 10 in the lowest tertile developed contralateral disease, yielding a relative risk of 4.69 for incident disease at the knee in the presence of obesity. Obesity is also a significant risk factor the development of features associated with OA at the knee in middle-aged and elderly people. Data from the Chingford study demonstrated...

Obesity as Risk for Progression ofOA

In particular, a reduction in the JSW is regarded as the hallmark of disease progression. Whereas cross-sectional studies examining the association between BMI and radiological JSW have reported conflicting results (10,11), obesity has been consistently associated with a longitudinal reduction in the JSW. Although obesity is a risk factor for longitudinal radiological JSN, the assessment of the JSW as an outcome measure for the progression of OA is often insensitive. Raynauld et al. found that over a 2-yr period, radiological assessment was unable to distinguish significant changes in the JSW in people with knee OA, despite a significant loss of articular cartilage volume (52). In contrast, MRI studies have revealed that as little as 2 change in cartilage volume may be reliably detected when a maximum of 6 individuals (patella), 10 (femur), 28 (medial tibia), and 33 (lateral tibia) are followed longitudinally (53). Although obesity is a risk factor for the progression of...

Nutrition and Weight Management

American Obesity Association 1250 24th St. NW, Suite 300 Washington, DC 20037 (202) 776-7711 www.obesity.org Office of Dietary Supplements National Institutes of Health Bethesda, MD 20892 2005 Dietary Guidelines available at Nutrition.gov The 2005 Revised Food Pyramid (sponsored by the USDA) www.mypyramid.gov

When You Need to Gain Weight

Between your three meals a day, consume two or three snacks. Include high-calorie foods that are rich in nutrients, such as peanut butter and milk shakes. Space your meals and snacks so that you eat more without feeling overly full. Use the Food Guide Pyramid (see page 5) as your guide to healthy eating, consuming the highest recommended number of servings. For example, try eating 11 servings of grains and three servings of dairy products every day. Choose high-calorie fruits (bananas, dried fruit, and canned fruit in syrup) and vegetables (olives, corn, and avocados). Make meal and snack times as pleasant as possible to eliminate feelings of boredom, loneliness, or stress that may be affecting your appetite. Put fresh flowers on the table. Invite a friend or a neighbor over for lunch or dinner. Play music that you like during meals. These practical tips can make the difference between struggling to eat and eating well.

Losing Weight Sensibly

Many overweight men have tried dieting and exercising to lose weight, with only modest success. Backsliding is easy, especially during the holidays or on special occasions. Successful weight loss depends on setting attainable goals and having reasonable expectations of meeting them. Losing 10 percent of your total body weight is an example of a sensible goal that you will be likely to reach. The sense of accomplishment that you feel will encourage you to keep the weight off and lose more if you desire. Most people should lose weight gradually a rate of 2 pounds per week is about right. If you have a serious weight-related health problem that requires you to lose weight faster, do so only under your doctor's supervision. How much you weigh is determined by a number of factors, including the amount and type of food you eat, whether you exercise, whether you eat in response to stress, your genetic makeup, your age, and your health. If you want to lose pounds and maintain a reasonable...

The Health Risks of Being Overweight or Underweight

More than half of all American men are overweight, and a third of all American men are obese (weigh more than 20 percent more than their ideal body weight). Being overweight is a major risk factor for a number of chronic diseases, including heart disease, high blood pressure, stroke, diabetes, and certain forms of cancer. Even a small reduction as little as 10 percent in body weight can decrease your chances of developing the most common chronic disorders as you get older. If you already have a health problem, losing weight can help you manage your condition. In some disorders, such as diabetes, weight loss can help reduce and even eliminate the need for medication. 70 pressure, and stroke if you keep your weight within a healthy range. However, Healthy where your body stores fat. If you are like most men, your body stores fat around the abdomen, and a large amount of abdominal fat raises your likelihood of developing heart disease and diabetes. Regular aerobic exercise (see page 56)...

Dietary Protein And Amino Acids

It is not possible to establish recommendations for cancer prevention based upon dietary protein level or source. Dietary protein can increase, decrease, or have no effect on tumorigenesis in various tumor models, suggesting that protein may exert very specific mechanisms of action that are unique to each target tissue and initiating agent (42,147-149). Very little research has focused on the role of dietary protein or amino acids in tumor angiogenesis. One mechanism whereby dietary protein intake may influence angiogen-esis is via dietary intake of the amino acid L-arginine, and subsequent modulation of nitric oxide (NO) production. NO is synthesized from L-arginine by the enzyme family, NO synthase (NOS). Recent investigations revealed that the NOS pathway is frequently upregulated in solid tumors of experimental animals (150-153), and the expression of different isoforms of NOS has been characterized in several tumor systems (150152,154). The synthesis of NO by endothelial cells is...

Recruitment of monocytes to adipose tissue in obesity

Although recent studies have established that obesity is associated with the accumulation of macrophages in adipose tissue of rodents and humans, the mechanisms that regulate this process are just being studied. The first step in the recruitment of mono-cytes to a tissue is the adhesion to endothelial cells. In human studies, obesity and impaired insulin sensitivity are associated with elevated circulating concentrations of cellular adhesion molecules, including ICAM-1, VCAM-1, and E-selectin (103-107). In vitro adipocyte-conditioned medium can directly u pregulate the expression of ICAM-1 and platelet-endothelial cell adhesion molecule (PECAM), and increase adhesion, migration, and chemotaxis of monocytes (97). Recently leptin and adiponectin have been shown to have opposing effects on endothelial cells leptin increases mono-cyte adhesion to endothelial cells, and adiponectin reduces expression of adhesion molecules and other proinflammatory molecules by endothelium (97,108). Several...

Dietary Lipids And Fatty Acid Patterns

The role of dietary lipid concentration, sources of fat, and specific fatty acid patterns on the incidence and progression of many cancers has been the source of much specula tion and investigation (6,7,21). The human and laboratory evidence is most convincing for a stimulatory effect of dietary lipid concentration, particularly a diet rich in saturated fats, on cancers of the colon and rectum (6,7,21). Less certain, but supported by many studies, are the positive relationships between diets rich in fat and cancers of the prostate, breast, lung, ovary, and endometrium (6,7,21). The possibility that diets rich in omega-3 fatty acids from marine sources have inhibitor properties for cancers has been postulated, and is currently an area of active investigation (6,7,21,109-114). Dietary lipid intake is primarily in the form of triacylglycerols (triglycerides), with one molecule of glycerol bound to three fatty acids. Dietary fatty acids vary in chain length (typically even numbered, 4-22...

Obesity

Lished that hyperinsulinemia, insulin resistance, and other obesity-related metabolic abnormalities are significantly associated with overall accumulation of fat in the body, there is now substantial evidence that the specific distribution of fat is important as outlined in Chapter 3. Excessive accumulation of fat in the upper body's so-called truncal region, or central obesity, is a better predictor of morbidity than excess fat in the lower body, the so-called lower body segment obesity10,12,13.

Weight gain

Edible oils increase in weight during the early stages of lipid oxidation as fatty acids combine with oxygen during the formation of hydroperoxides. The increase in weight of a heated sample during storage can be used to determine the induction time of the fat. Rapid weight gain occurs after the induction period, or the time for a certain weight increase can be determined. However, decomposition of hydroperoxides leads to a weight reduction, and the fat is severely oxidised at the end of the induction time.

Gender and obesity

Obesity classification and treatment recommendations are the same for men and women (Table 1) (1) however, at any given BMI women throughout the world are more likely to have greater amounts of adipose tissue than men (9) and have higher rates of obesity owing to biological differences (10). In the United States, proportionate increases in obesity prevalence have occurred for both men and women 20 to 74 yr of age since 1960, and women have had higher prevalence rates in all age groups in each of the national surveys (Table 3).

Childhood obesity

There has been a threefold increase in childhood obesity in the United States in the past three decades (12). Coinciding with this increase has been an increase in prevalence for type 2 diabetes, hypertension, gallbladder disease, hyperlipidemia, orthopedic complications, sleep apnea, and nonalcoholic steatohepatitis in children. Obese children are predisposed to adult obesity and have increased risks for adult obesity-related diseases (19). Approximately 30 of obese adults became obese during childhood, and 80 of obese adolescents become obese adults (20). No single cut-point for obesity classification can be used for children because between birth and approx 20 yr of age, height and weight and thus, BMI vary by age. To address this children (age 2-11) and adolescents (age 12-19) are classified as at risk of overweight or overweight if they are at or above the 85th or the 95th percentile, respectively, for their age and gender using the 2000 Centers for Disease Control and Prevention...

Dietary Restriction

In patients with food hypersensitivity, food-allergen avoidance results in improvement of AD. Sampson and coworkers have shown that following a strict avoidance diet of relevant food allergens patients experience symptomatic relief of pruritus and clearing of skin rash. Because of the high false-positive rate of prick skin testing and standard RAST for food allergens, an elimination diet followed by a blinded (single- or doubleblind) or open food challenge should be performed to confirm clinical reactivity to a particular food, unless a convincing history of anaphylaxis is obtained. An exception to this rule is when an elevated CAP-FEIA is obtained that demonstrates a greater then 9095 likelihood that a patient will have a positive food challenge. Several investigators have shown the utility of this test for the diagnosis of food allergy without the need for food challenge. Improvements have been made regarding assessment for the development of tolerance among food-allergic patients....

Okines in and Uisease

Edited by Adrianne Bendich and Richard J. Deckelbaum, 2005 The Management of Eating Disorders and Obesity, Second Edition, edited by David J. Goldstein, 2005 The Management of Eating Disorders and Obesity, edited by David J. Goldstein, 1999 Vitamin D Physiology, Molecular Biology, and Clinical Applications, edited by Michael F. Holick, 1999

Implications of leptin signal transduction

In contrast to the robust response to energy deprivation mediated centrally by low leptin, an increase in leptin in the overfed or obese range has little effect on neuronal or physiological functions (65). This resistance to leptin in diet-induced obesity may involve inhibition of leptin signal transduction through leptin-mediated activation of SOCS-3 or PTP1B (59,63,67). Expression of neuropeptide targets of leptin such NPY and POMC have been shown to be dysregulated and the transport of leptin across the BBB is impaired in obese rodents, but whether these are relevant to the onset or progression of human obesity remain to be determined (68-70).

Leptin action in peripheral tissues

Minokoshi et al. (103) demonstrated a biphasic action of leptin on muscle after intravenous injection. The initial increase in AMPK activity in soleus muscle occurred rapidly within 15 min, and was not affected by sympathetic blockade (103). In contrast, a later, more sustained, increase in AMPK activation (60 min to 6 h) was mimicked by intrahypothalamic leptin injection and abolished by sympathetic blockade (103). A direct action of leptin was confirmed by incubating soleus muscle with and without leptin and demonstrating a robust leptin-dependent stimulation of AMPK activity. Direct or indirect activation of muscle LEPRb by leptin results in phosphorylation and activation of AMPK (103). AMPK phosphorylates acetyl-CoA carboxylase (ACC), leading to inhibition of ACC activity and thus decreasing formation of malonyl-CoA, which in turn disinhibits carnitine palmitoyltransferase 1 (CPT-1), a critical step for translocation of fatty acids into mitochondria to undergo -oxidation (104). It...

Broad Spectrum Antibiotics Also Perturb Our Microbiomes

Our bodies contain trillions of bacteria that have evolved to live in humans. More than 38,000 different species live in the human digestive tract, and bacteria occupy at least 20 distinct niches on our skin. The microbes carried by each host are collectively called a microbiome. Humans have evolved to take advantage of the bacteria, and the bacteria gain advantage from us. Box 1-2 describes examples relating to obesity and pain. Some bacteria help humans digest food, whereas others protect from particular pathogens. For example,

Triple reuptake inhibitors

Triple reuptake inhibitors (TRIs), which increase DA levels in addition to serotonin and NE, are expected to be as efficacious as monoamine oxidase inhibitors (MAOIs) without being limited by the same side effects and dietary restrictions that accompany MAOI use. The rationale for including DAT inhibition is partially based on the well-established role of dopaminergic systems in motivation and reward. Anhedonia and lack of interest, which are core symptoms of MDD, result from dopaminergic impairment in corticolimbic areas, and depressed patients have been shown to have decreased DA release by nerve terminals in the mesolimbic system

Common Exercise Related Injuries

Weight-bearing exercise such as jogging, running, or even brisk walking can place a lot of stress on joints and muscles. If you are overweight, you may be at greater risk for discomfort, pain, or injury from weight-bearing exercise early in your fitness program or when increasing your level of intensity or duration. Overuse injuries affect most men who exercise from time to time. There are a number of things you can do to prevent common exercise-related injuries such as sprains, strains, inflammation, and pain. Minor injuries usually can be treated with simple first-aid measures (see RICE routine, page 65). However, if you have a more serious injury, such as a broken bone, go directly to a hospital emergency department.

Medicinal chemistry

Several reviews 8,12,14-16,66 of the 5-HT6 literature have been published covering research prior to 2006, consequently this section will primarily focus on more recent publications with salient points from the earlier literature. 5-HT6 ligands may be characterized as agonists, antagonists and inverse agonists using in vitro systems. However, their in vivo pharmacological effects in pre-clinical models of both cognitive function and body weight control can appear independent of functional behavior since both agonists and antagonists exhibit similarly favorable effects 56 . These observations pose unique challenges for the selection of compounds for pre-clinical development. Noteworthy, most of the in vitro work has been carried out with cloned receptors in stably transfected cell lines. Future pharmacological characterization in native tissue may shed light on this anomaly.

Plasma Adiponectin Levels and Adiposity

Unlike most adipokines, adiponectin levels in the circulation are paradoxically decreased in obese subjects (63). On the other hand, weight reduction by gastric partition surgery or calorie restriction leads to an increase in plasma levels of total adiponectin (64). There is a strong inverse correlation between plasma levels of adiponectin and measures of adiposity, including body mass index (BMI) and total fat mass (15).

Classification and evolution of increased cardiometabolic risk states

It has been accurately observed that certain risk factors in humans appear to 'cluster' with clinical states such as obesity and type 2 diabetes. Specifically, this risk factor clustering, and the association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition1. Many names have been provided to describe this clinical state including 'metabolic syndrome', 'syndrome X', and 'insulin resistance syndrome'1. The particular names that refer to this risk factor clustering describe the human condition characterized by the presence of co-existing traditional risk factors for cardiovascular disease (CVD), such as hypertension, dyslipidemia, glucose intolerance, obesity, and insulin resistance, in addition to non-traditional CVD risk factors, such as inflammatory processes and abnormalities of the blood coagulation system2-6. Table 1.1 lists conditions and components associated with the clustering of risk factors. As seen, the components...

Adiponectin as a potential therapeutic target

As discussed above, promising results obtained from numerous animal experiments and human epidemiological studies support the role of adiponectin as a potential drug target for developing novel therapeutics against a panel of obesity-related chronic diseases. However, adiponectin is an abundant plasma protein (5-30 p.g mL). The production of recombinant adiponectin is also challenging because of the complex tertiary and quaternary structure of the protein and the distinct activities of the different isoforms. Direct supplementation of recombinant adiponectin in human subjects would be extremely expensive. An alternative approach is to use pharmacological or dietary intervention to increase the suppressed endogenous adiponectin production in obesity, or to enhance adiponectin actions in its target tissues. In this respect, it is interesting to note that the PPARy agonists thiazolidinediones (TZDs), such as rosiglitazone and pioglita-zone, which increase adiponectin production in both...

Potential Clinical Applications

Obesity - The role of the 5-HT2c receptor in regulation of appetite is based on several keys lines of evidence. First, the 5-HT2c receptor is enriched in nuclei of the hypothalamus that regulate satiety. 5-HT2C agonists inhibit food intake even after chronic administration in rodents (34,35). Whereas selective antagonists block these effects, paradoxically, they alone do not increase food intake and weight gain (12,36,37). 5-HT2C knockout mice developed delayed-onset obesity and hyper-insulinemia, and are insensitive to the hypophagic effects of fenfluramine (38,39). Finally, nonselective 5-HT2c agonists reduce food intake and weight in humans (40). the paucity of the 5-HT2C receptors in peripheral tissues, the 5-HT2c receptor is unlikely involved with these illnesses. Fenfluramine's ability to serve as a 5-HT transporter substrate is hypothesized to contribute to PPH whereas the mitogenic 5-HT2b agonist properties of norfenfluramine have been implicated in VHD (43-45). Selective...

What is moderate drinking

While it is generally agreed that we should do all things in moderation 58 , there is less agreement about the precise definition of 'moderate' drinking. Use of different sets of drinking categories in different reports has resulted in different interpretations, and the number and boundaries of categories appears to be determined by the sample size available in the study. Classification of moderate alcohol consumption ranges from a half a drink per day (or less) in some studies, up to six drinks a day in others 59 , Data from the National Health Interview Survey 52 demonstrated that people with different drinking habits perceived 'moderate' drinking differently. Only 25 of men who drink 3 or more drinks per day, in comparison to 56 of other men, considered 2 or fewer drinks per occasion as moderate. Likewise, only 6 of the women who drink at least 2 drinks per day (vs. 27 of other women) perceived moderate drinking as 1 drink or less per occasion. The National Health and Medical...

Adipokines with vasoactive or inflammatory effects

IL-6 and TNF-a are among the well-known cytokines consistently found to be increased in obesity, comprising elevations both at the adipose tissue expression level and the bloodstream (11,27). The list of factors shown to be implicated either directly or indirectly in the regulation of vascular homeostasis through effects on blood pressure, inflammation, atherogenesis, coagulation, fibrinolysis, angiogenesis, proliferation, apoptosis, and immunity has increased at a phenomenal pace (5-12,14-18,21,24). By definition, adipocytokines are cytokines produced by adipocytes. Although adipose tissue secretes a variety of factors, strictly speaking, not all of them can be contemplated as cytokines. Therefore, the less strict term of adipokines has been coined to include a wider range of factors. Leptin, adipsin, resistin, adiponectin, and visfatin fall within the category that satisfy the more strict requirements to be properly classified (11).

Observational Study Results

Since the publication of the Seven Countries study, others have examined the association between the consumption of Mediterranean dietary pattern and risk of CHD. Notably, the characterization of the diet has required development of a Mediterranean-diet score that incorporates salient characteristics of this diet.29 A scale of 0-9 was created and indicates the degree of adherence to the traditional Mediterranean diet. Table 2.1 Characteristics of the 1960 Crete, a.k.a Mediterranean diet, compared with the average diet consumed by the United States men (age 40-59 years) and diets tested within the setting of randomized clinical trails Table 2.1 Characteristics of the 1960 Crete, a.k.a Mediterranean diet, compared with the average diet consumed by the United States men (age 40-59 years) and diets tested within the setting of randomized clinical trails Dietary pattern 24 h dietary Dietary pattern Table 2.2 Dietary features characteristic of the traditional Mediterranean diet29 High...

Tumor Necrosis Factora

TNF-a was originally identified as a macrophage product implicated in the metabolic disturbances of chronic inflammation and malignancy. Later on, its biological actions were shown to further extend to anorexia, weight loss, and insulin resistance (7). Elevated adipose tissue expression of TNF-a mRNA has been reported in different rodent models of obesity as well as in clinical studies involving obese patients (23). TNF-a mRNA expression is positively correlated with body adiposity as well as with hyperinsulinemia, showing positive associations with fasting insulin and triglyceride concentrations. TNF-a inhibits the expression of the transcription factor CCAAT enhancer binding protein-a (CEBPa) and the nuclear receptor peroxisome proliferator-activated receptor (PPAR)y2 (8,12,14). Furthermore, TNF-a stimulates the nuclear factor- kB transcription factor (NFkB), which orchestrates a series of inflammatory events, including expression of adhesion molecules on the surface of both...

How are laryngoscopes used

Laryngoscopes are usually left-handed tools designed to facilitate visualization of the larynx. Short handles work best for obese patients or those with thick chests or large breasts. Laryngoscope blades come in various styles and sizes. The most commonly used blades include the curved Macintosh and the straight Miller blades. The curved blades are inserted into the vallecula, immediately anterior to the epiglottis, which is literally flipped out of the visual axis to expose the laryngeal opening. The Miller blade is inserted past the epiglottis, which is simply lifted out of the way of laryngeal viewing.

Describe the indications for an awake intubation

If the physical examination leaves in question the ability to ventilate and intubate once the patient is anesthetized and paralyzed, consideration should be given to awake intubation. Patients with a previous history of difficult intubation, acute processes that compromise the airway (e.g., soft-tissue infections of the head and neck, hematomas, mandibular fractures, or other significant facial deformities), morbid obesity, or cancer involving the larynx are reasonable candidates for awake intubation.

H3 antagonists with a dual mechanism

There is an increasing appreciation for the complexity of the H3 receptor (species sequence differences, splice isoforms, localization, constitutive activity) that adds to the challenges in drug discovery. However, despite these complexities, significant advances have been made in medicinal chemistry to identify novel amine-based cores for drug design, and in synthesizing a large number of highly potent and selective H3 antagonists with efficacy in a variety of preclinical models of cognition, sleep and obesity. To date no peer-reviewed clinical efficacy data for an H3 antagonist are available, reflecting the numerous hurdles and challenges in developing safe drug-like H3 antagonists. Since the H3R has the potential to treat a large number of CNS diseases, additional efforts with newer compounds will no doubt lead to a better understanding of the target and the properties required for therapeutic efficacy. 64 K. Malml f, V. Golozoubova, B. Peschke, B. S. Wulff, H. H. Refsgaard, P. B....

Plasminogen Activator Inhibitor1

Although PAI-1 is primarily derived from platelets and the endothelium, it has been demonstrated that most of the elevated concentrations of this regulatory protein of the coagulation cascade in inflammatory and obese states is attributable to an upregulated expression by adipose tissue itself (12,58). Therefore, WAT represents a quantitatively relevant source of PAI-1 production, with consequently increased circulating concentrations present in obesity. Stromal cells have been shown to be the main PAI-1 producing cells in human fat, with a fivefold higher expression in the visceral than in the subcutaneous depots, which is in agreement with the strong relationship observed between circulating PAI-1 concentrations and visceral fat accumulation (59). However, whether adipose tissue itself directly contributes to circulating PAI-1, or whether it exerts an indirect effect via adipokines, such as TNF-a , IL-1 , and TGF- , to stimulate PAI-1 production by other cells has not been clearly...

Potential Therapeutic Applications

Body Weight Regulation - NPY has potent effects on physiological and endocrine systems that modulate energy homeostasis (2,3,7). NPY has been identified as the most potent naturally occurring orexigenic peptide. Over the last few decades, it has been demonstrated in a number of species that administration of NPY to the brains of satiated animals induces a tremendous surge in food consumption (8,9). Although not entirely understood, this feeding response is thought to be mediated by the NPY Y1, NPY Y5 or both receptors, each of which is expressed in the hypothalamus. Central administration of NPY also lowers energy expenditure (10,11). Increased food consumption and decreased energy expenditure results in a state of positive energy balance that will promote adipose tissue accretion. Indeed, chronic central administration of NPY to normal rats results in a pathophysiological profile similar to that in human obesity, including hyperphagla, increased adiposity, hyperleptinemia,...

Vascular Endothelial Growth Factor

VEGF is a well-recognized angiogenic factor that induces migration and proliferation of vascular endothelial cells (12). VEGF is encoded by a single gene however, four isoforms are produced by alternative splicing, which have been implicated in both normal blood vessel development and in pathogenic neovascularization and atherosclerosis. In obese patients serum concentrations of the 164-amino-acid-long isoform has been observed to be dependent on intra-abdominal fat accumulation (70). VEGF mRNA expression has been identified in various cell types, including endothelial, epithelial, and mesenchymal cells. Recently, attention has been focused on the altered expression profile of VEGF in omental WAT obtained from obese individuals (71). Given the growth potential of adipose tissue, it is not surprising that adipocytes express an angiogenic factor like VEGF implicated in vascular bed expansion to support fat mass accretion. The participation of VEGF in vascular inflammation and remodeling...

Induction Of Aox Enzymes

The validity of these urinary measurements of oxidative DNA damage must be considered. The level of 80HdG in urine is presumably unaffected by the diet because nucleosides are thought not to be absorbed from the gut. However, this question, and the question as to whether any 80HdG is metabolized to other products in humans, has not been rigorously addressed in the Breath excretion of ethane and pentane, minor end products of lipid peroxidation, is difficult but not impossible (78) to measure in humans because of the problem of contamination of the atmosphere by these gases, leading to their partitioning into body fat stores (79). Particular problems with pentane include the fact that it is metabolized by cytochromes P450 (78,80) and that GC columns frequently used to separate ' 'pentane'' for measurement can fail to separate it from isoprene, a hydrocarbon also excreted in exhaled air (79,81,82). Indeed, the levels of excreted real pentane seem close to zero in most humans (79,81,82)....

Molecular links underlying the adiposityinflammationimmunity cluster

The body of knowledge of the pathophysiological effects of adipokines on vaso-activity and inflammation has been gathered from different types of studies, including epidemiological observations, animal model experiments, in vitro approaches, and microarray application. The consistent interrelationship between several adipokines with known effects on inflammation, atherosclerosis, and insulin resistance provides support for the crucial role of adipose tissue in the regulation of obesity-linked CV derangements. Although the existence of inflammatory events is well-known to exert a The molecular mechanisms linking the adiposity-inflammation-immunity cluster are complex and their understanding is in continous evolution. The triad of obesity-insulin resistance-CVD is interwoven in a setting of inflammation, endothelial dysfunction, and atherosclerosis. Obesity is characterized by a low-grade systemic inflammation and a hypercoagulable state contributing to atherosclerosis. Endothelial...

Alcohol intake type of drink and risk of CHD events and mortality

+ adjusted for age, social class, smoking, physical activity, body mass index, lung function evidence of CHD on questionnaire, diabetes and regular medication. + adjusted for age, social class, smoking, physical activity, body mass index, lung function evidence of CHD on questionnaire, diabetes and regular medication.

Protein tyrosine phosphatase 1B PTP1B inhibitors

PTP1B negatively regulates insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) phosphorylation. Mice that lack the PTP1B gene have increased insulin sensitivity with resistance to weight gain on a high-fat diet and are otherwise normal. This unique combination of desired attributes has driven an intense search for PTP1B inhibitors for treatment of both T2D and obesity. The discovery of effective inhibitors of PTP1B has proven challenging, due to both the selectivity requirements over other protein tyrosine phosphatases, particularly T-cell protein tyrosine phosphatase (TC-PTP) with which it shares high sequence homology near the catalytic site, and the need for potent antagonists to incorporate polar phosphate mimics, thus limiting cell penetration. The Abbott team

Clinical Feeding Study Results

The Lyon Diet Heart study and the Indo-Mediterranean diet trial relied on behavior modification strategies to promote adoption of the Mediterranean diet plans to participants. Compliance with dietary recommendations was hard to assess and effects of on-traditional CVD risk factors hard to ascertain. In fact, in the Lyon Diet Heart study, end-of study assessment of the traditional CVD risk factors including blood pressure and lipids, were not different between groups.8 This finding was unexpected as emphasis on unsaturated fatty acids rather than saturated or trans-fatty acids would be expected to beneficially affect serum lipid levels.23 Likewise, dietary patterns emphasizing fruits and vegetables have been shown to substantially lower blood pressure and are discussed next.2 Hence determining the effects of the Mediterranean diet on traditional CVD risk factors, including blood pressure and lipids, and on markers of oxidative stress, may be best determined in a different setting...

Leptin Regulation of Monocytes Macrophages

Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflamma-tory cytokines both in vivo and in vitro, whereas exogenous leptin upregulated both phagocytosis and the production of cytokines (18). Furthermore, phenotypic abnormalities in macrophages from leptin-deficient, obese mice have beeen found (19). More important, leptin deficiency increases susceptibility to infectious and inflammatory stimuli and is associated with dysregulation of cytokine production (16). More specifically, murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. In this context, leptin levels increase acutely during infection and inflammation, and may represent a protective component of the host response to inflammation (20).

Leptin and pathophysiology of the immune system

The same immune deficiency observed in starvation has been found in human obesity syndromes caused by a deficiency of leptin production or leptin action (46). In addition, leptin administration in obesity caused by lack of leptin can restore immune function as observed in a similar way as that seen in starving conditions (6-8). On the other hand, an excess of leptin in the circulation that occurs in obesity and overweight could have a role in pathological conditions mediated by an excess of immune response (73). This proinflammatory state may be relevant for cardiovascular disease and the risk for myocardial infarction that is increased in obese people. Moreover, leptin, together with other adipokines, could be a common link between obesity and cardiovascular risk in metabolic syndrome. Because obese people do not respond to leptin properly, central versus peripheral leptin resistance may underlie the pathophysiology of obesity, and therefore, the study of leptin signaling at central...

Leptin in liver and kidney immunemediated disorders

It has been also demonstrated that leptin is a renal growth and profibrogenic factor and therefore can contribute to renal damage, characterized by endocapillary proliferation and subsequent development of glomerulosclerosis (33). This is more likely to happen in pathophysiological situations characterized by high circulating leptin levels, such as diabetes and obesity (33). This evidence suggests that leptin may also exert propathogenic effects in immune-mediated disorders of the kidney. Strategies aimed at reducing leptin may envisage novel therapeutic approaches able to delay immunemediated kidney disorders.

The Characteristics of Individuals Suffering from BDD

People with eating disorders and obesity have similar features to those of BDD patients, such as frequently weighing themselves, checking in the mirror and excessive weightlifting or exercising. Other symptoms might include avoidance of mirrors or reflective surfaces, constant scrutinizing the appearance of others, excessive grooming (Fig. 18.1), seeking reassurance from parents or dependence on others for constant reassurance, touching, picking or fiddling with the defect, repeated measuring or photographing of the defect, avoidance of social contact, withdrawn, housebound truancy, avoiding athletics, boating or drama classes and failure to hold employment.

Summary and Conclusion

The Mediterranean dietary patterns are associated with lower CHD rates and with improved CHD risk factors. In the interpretation of observational data, it is often difficult to separate the effects of diet from other factors, e.g., smoking and physical inactivity, that likely account, in part, for observed differences in CHD risk. Nonetheless, the totality of evidence documenting a beneficial impact of Mediterranean dietary patterns on CHD risk is remarkable and consistent in both the original Seven Countries Study and in recent studies of populations with Western variants of the original diet. Cardiovascular disease risk reduction by consumption of the Mediterranean diet may be mediated through demonstrated effects on traditional CVD risk factors of through effects of factors which reduce oxidative stress. Overall, such findings have tremendously important public health implications. Despite broad variation in geography, lifestyle, and locally available foods, it is evident that for...

How to Get a Good Nights Sleep

Healthy may find that they simply don't need as much sleep as they did when they were younger. Overweight men may have problems getting a good night's sleep. Snoring also may contribute to a loss of sleep. Sleep apnea (a condition characterized by brief episodes of interrupted breathing during sleep) is another common reason for losing sleep. Many people who have sleep apnea find it difficult to stay awake during the day. However, the most common reason for an occasional night of lost sleep is worry or anxiety.

Neuropeptide Y family modulators

The published data on Y5R antagonists have provided a conflicting picture of the role of this receptor in body weight regulation. Several antagonists have been shown to decrease food intake in various rodent models, but were later found to be an-orectic in Y5R KO mice 72 . Other antagonists with good central exposure were inactive in DIO rodent models despite high binding affinities and good functional potencies 73 . In the last year, however, several reports have appeared that suggest Y5R may be physiologically important in obesity. Most noteworthy, extensive effort has been devoted to proving specificity-of-action. A tricyclic derivative 38 (L-152804) has been studied in different rodent models of obesity 76,77 . This compound showed moderate Y5R binding affinity (mY5R 44 nM, rY5 K 31 nM, Ca2+ IC50 210 nM) and was claimed to have little off-target activity (no significant cross reactivity with 120 other binding assays and seven enzyme assays). Compound 38 decreased body-weight gain...

Aminergic Receptor Modulators 41 5HT2CR agonists

The anti-obesity effects of several different 5HT2CR agonists have been recently reported. The tetracyclic analog 45 (WAY163909) is a novel 5HT2CR full agonist that was discovered by using a pharmacophoric model for 5HT2CR binding activity. Compound 45 showed greater than 20-fold binding selectivity for 5HT2 CR over both 5HT2A receptor (5HT2AR) and the 5HT2B receptor (5HT2BR) 96 . Functionally, the compound stimulated intracellular calcium mobilization with an EC50 value of 8nM. It showed no agonist activity at 5HT2AR, but partial agonist activity at 5HT2BR (EC50 185 nM, Emax 40 ). It also pro duced dose-dependent reductions in food intake in normal SD rats, an effect blocked by a 5HT2CR antagonist. In a 10-day study, 45 caused a 56 decrease in body weight, with reductions also observed in triglyceride levels. No toleration of the anorectic effect was observed, in contrast to studies with other 5HT2CR agonists 97 .

Vitamin E In Diabetes

Vitamin E (RRR-a-tocopherol) is the most important lipid-soluble antioxidant, which protects lipoproteins and cell membrane lipids from oxidative damage. This ability is coupled to other antioxidant systems (vitamin C, glutathione, lipoic acid) that can recycle the vitamin E radical (19). In the absence of such systems, vitamin E can behave as an oxidant (20). Dietary vitamin E is transported to the liver and secreted from the liver within very-low-density lipoproteins (VLDL). It is distributed among VLDL and LDL during the transfer and metabolism of the lipoprotein lipids (21). Thermodynamic partitioning also permits some transfer into high-density lipoproteins (22). An important part of vitamin E is constituent of cell membranes where it protects the lipid moiety against peroxidation (23).

Fivemembered ring pyrazole bioisostere CB1 antagonists

Two patent applications concerning 1,5-diaryl pyrrole-3-carboxamides have also been filed 46,47 . Although one of these does not specifically claim use as CB1 antagonists, but rather for compounds treating obesity, the compounds described are closely related to SR141716. This publication reports a significant decrease in food consumption following oral administration of compound (16). Conforma-tionally restrained analogs of these molecules were also prepared by bridging the methyl group with the adjacent amide nitrogen, leading to compounds such as (17) 48 . Other patent applications describing pyrroles and imidazoles have also been published by an independent group. In these patents that each include more than 300 examples, the substituent in position 1 includes both aromatic and non-aromatic groups such as methylcyclohexyl, and the substituent in position 5 may be a substituted phenyl or thiazole ring 49,50 .

Nonimidazole H3 Receptor Antagonists

Further work in this series identified the biphenyl nitrile 6 9 . Unlike the piperazine amide 4, this compound is a potent ligand for both the rat and human H3 receptor (pKi rat 7.87, pKi human 8.56) and is selective for the H3 receptor over the Hi and H2 receptors. Furthermore, 6 was the first non-imidazole H3 antagonist to show weight loss in a diet-induced obesity model 10 . In a 28-day study in mice fed a high fat diet, 6 (15 mg kg) reduced weight to a level comparable to mice fed a low fat diet. Total body fat as measured in the fat pads was reduced and the animals displayed normal insulin tolerance. Consistent with a central mode of action, 6 attains extremely high concentrations in the brain (brain plasma 160 at 1 h following 5 mg kg i.v. administration).

Acc Inhibitors In Longterm Efficacy Studies

The second study with 2 was performed in diet-induced obese (DIO) C57Bl6 J mice. Compared to control DIO mice, mice treated with 2 showed significantly less weight gain over the course of the 6-week study. However, mice treated with 2 had liver triglyceride and total cholesterol levels that were identical to untreated DIO mice. In a glucose infusion clamp study, the glucose infusion rate was slightly higher for the treated animals ( 10 ) than for the untreated DIO mice. The study concluded that treatment with 2 had a moderate effect on improving the diabetic phenotype of DIO mice 49 . In addition to these studies with 2, the effects of the dual ACC1 ACC2 inhibitor 1 in in vivo efficacy studies in high-fat-fed C57Bl6 J mice have been reported 50 . In mice fed a high-fat chow diet, 1 administered in-diet (50 and 100 mg kg day) dose-dependently reduced body weight gain relative to a high-fat chow-fed control group. Mice treated with 1 also had significantly higher levels of...

Physiologic systems regulating energy balance including the endocannabinoid system

It is well established that obesity and insulin resistance are associated with an increased risk for developing type 2 diabetes in addition to developing other cardio-metabolic risk factors1-4. Fortunately, over the recent past, there has been a rapid and substantive increase in our understanding of the underlying physiologic systems and molecular pathways modulating these conditions. Specifically, key regulators of energy balance and insulin signaling have been elucidated that have aided greatly our understanding of the link between obesity and insulin resistance. As such, the concept of obesity may be simple to grasp in that it develops over time when we take in more calories than we burn, but insight into the mechanisms behind this observation has revealed systems that are complex and highly integrated5. Specifically, the epidemic of obesity that is occurring globally indicates the inability of homeosta-tic mechanisms to offset a sedentary lifestyle and increased caloric intake6,7....

Human inflammatory bowel disease

Abnormalities of adipose tissue in the mesentery, including adipose tissue hypertrophy and fat wrapping, have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Desreumaux and colleagues evaluated this phenomenon and quantified intra-abdominal fat in patients with CD vs UC by using magnetic resonance imaging (51). By applying this technique they were able to demonstrate a significant accumulation of intraabdominal fat in patients with CD. This mesenteric obesity, present from the onset of disease, is associated with overexpression of PPARy as well as TNF-a mRNA, as evaluated by RT-PCR studies (51). In a subsequent study, the same group could demonstrate an overexpression of leptin mRNA in the mesenteric adipose tissue in inflammatory bowel disease, whereas no difference could be detected between UC and CD. The...

Potential Therapeutic Indications

Initial studies showing higher expression of MCH in hypothalami of leptin deficient (Lepob ob) and hypoleptinemic (fasted) mice, and that i.c.v. administration of MCH to rats stimulates food intake, established a role for MCH in feeding 37 . Several groups have since confirmed the hyperphagic effect of acute central administration of MCH in both mice and rats 38-41 , as well as the over-expression of MCH in genetic models of leptin resistance 42,43 . Sub-chronic (7-14 days) central infusion of MCH to mice on a high fat diet induced persistent hyperphagia accompanied by increased adiposity, hyperinsulinemia and hyperleptinemia 44,45 while i.c.v. infusion of a potent MCH1-R peptide agonist to rats produced similar effects 46 . Consistent with these findings, transgenic eutopic over-expression of MCH produces an obese, insulin resistant and hyperphagic phenotype in mice on a high fat diet 47 . Deletion of the pmch gene, which generates an animal null for MCH as well as NEI and NGE,...

Aflatoxin Exposure in the South American Population

Evaluation of AFL exposure by measuring toxin levels in contaminated foods can be difficult to interpret due to the heterogeneous distribution of AFLs. Additionally, the dietary intake of a given food can be highly variable and unreliably reported. Genetic variability in AFB1 metabolism may also influence the level of exposure at the individual level therefore, an alternative for evaluating AFL exposure is to estimate levels using specific biological markers (biomarkers) based on an understanding of the metabolism of the compound. For AFB1, these include aflatoxin-N7-guanine (AFB1-N7-gua) in the urine, or aflatoxin-albumin (AFB1-alb) in the blood. Using the AFB1-alb biomarker assay approach, a study was carried out by Haas et al.34 to assess the level of exposure to AFB1 in a Brazilian population. A blood sample was taken from urban residents (n 50 ages 18 to 52) in 1999 at the Blood Center of Antonio Carlos de Camargo Hospital, Sao Paulo. Serum albumin was extracted and digested and...

Small Stomach Syndrome

Dietary treatment is often successful and consists of increasing the frequency and decreasing the size of the meals, adding supplemental vitamins, iron, and pancreatic enzymes. Surgical treatment aims at increasing gastric capacity by creating a gastric reservoir for the patients with a Hunt-Lawrence pouch (15) or the Tanner Roux-19 pouch (16). Both of these reconstructions carry the risk of stasis and ulceration, and are performed only in patients with severe symptoms that have failed conservative management.

Small molecule MCH1R antagonists

A second small molecule antagonist, SNAP-7941 (6, Kb 0.5 nM), demonstrated similar effects to those of T-226296 upon intraperitoneal injection 59 . Specifically, i.p. administration to lean rats suppressed the orexigenic effect induced by i.c.v. administration of MCH. Chronic administration to diet induced obese (DIO) rats (10 mpk, b.i.d.) suppressed food intake, providing a 26 weight reduction over 28 days (relative to controls). This contrasted with D-fenfluramine treatment wherein a pronounced hyperphagia and weight loss over 7 days was followed by a rebound in both by day 14. Though neither T-226296 nor SNAP-7941 were tested in MCH null mice to confirm that the observed effects are MCH1-R specific, radiolabelled SNAP-7941 was shown to specifically bind to MCH1-R in several brain sections. In conjunction with the anorectic effects, SNAP-7941 also exhibited an-xiolytic and antidepressant properties in forced swim and Vogel Conflict tests 60 . Derivatives of SNAP-7941 lacking...

Postvagotomy Diarrhea Syndrome

Vagal innervation is an important factor in the control of pancreaticobiliary secretion and intestinal absorption. Truncal vagotomy may result in excessive small bowel secretions or bile acids with resulting diarrhea. Diarrhea occurs in up to 25 of patients following a complete (truncal) vagotomy with gastric drainage or resection (17). Less than 2 of patients have incapacitating symptoms. The syndrome is characterized by frequent watery stools, usually unrelated to meals, and occurring at night. Medical therapy includes dietary alterations with low fluid content, frequent feedings, increasing dietary fiber, and adding substances such as pectin to slow intestinal transit. Medications include cholestyramine, which may help bind bile salts, and somatostatin, which is effective in some patients. Surgical therapy is rarely recommended, but when needed, consists of interposition of a 10 cm antiperistaltic jejunal limb 100 cm distal to the ligament of Treitz (18).

Observational Epidemiology

Several large cohort studies have evaluated the relationship between vitamin E intake and incidence of CHD. The largest of these is the Nurses' Health Study (NHS), a cohort study of more than 87,000 U.S. female nurses aged 34-59 years with no history of CVD.21 Dietary antioxidant intake and use of antioxidant vitamin supplements were ascertained through a semiquantitative food frequency questionnaire administered at baseline in 1980 with information on antioxidant supplements updated biennially. After 8 years, women in the highest quintile of vitamin E intake had a 34 lower risk of CHD (nonfatal MI and fatal CHD) compared with those in the lowest quintile (P for trend < 0.001). It was vitamin E supplementation - not dietary intake - that was associated with lower risk. Participants who took at least 100 IU of vitamin E supplements per day for more than 2 years experienced reductions of 40 or more in the risk of CHD, alter adjustment for age and cardiac risk factors. These results...

Adipose tissue and inflammation

Recent studies have revealed that inflammatory responses contribute to the development of a variety of common diseases, including atherosclerosis and metabolic diseases, including diabetes mellitus. On the other hand, adipose tissue has been recognized to secrete bioactive substances that relate to inflammation. TNF-a is a typical cytokine that plays a major role in inflammatory cellular phenomena. Since Uysal et al. first reported that adipose tissue secretes this cytokine and proposed it as one of the candidates for molecules inducing insulin resistance (25), TNF-a has come to be recognized as an important adipocytokine. It has been shown that adipose TNF-a mRNA and plasma TNF-a protein are increased in most animal models and in humans with obesity and insulin resistance (25,26). Neutralizing TNF-a in obese rats with a soluble TNF-a receptor-immunoglobulin G fusion protein markedly improves insulin resistance (27). These results indicate that higher production of TNF-a in...

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