Showing papers in "Basic life sciences in 1993"

Use of bioimpedance spectroscopy to determine extracellular fluid, intracellular fluid, total body water, and fat-free mass.

Abstract: The use of bioelectrical methods for estimating human body composition has been of interest since the 1960s. It is theoretically possible to measure the extracellular fluid (ECF) and intracellular fluid (ICF) volumes with bioimpedance spectroscopy. Fundamental to this is a basic understanding of the electrical properties of living tissue. Living tissues have distinct frequency dispersions which result from different mechanisms of structural relaxation. β dispersion, which occurs at low radio frequencies and represents the capacitive characteristics of the cell membrane, is of interest in the estimation of ECF and ICF. Due to high cell membrane capacitance (CM) at low frequencies there is little conduction occurring in the ICF compartment, thus, conductivity is governed by the properties of the ECF. High frequency currents show little effect due to cell membrane capacitance so current flows through both ECF and ICF more uniformly and proportionally to the relative conductivities and volumes of the compartments. Resistance to an alternating electrical current can be regarded as a vector with both direction and size and represents a point in a plane where the distance from the point to the origin is the absolute value of Z (impedance =√(R2 + X2) R = resistance X=reactance); arctan (X/R) is its phase angle (θ)1. When Z of a circuit is measured and the frequency is varied a series of values are derived which can be represented as points on a curve. The curve formed by these points can be translated into an equivalent electrical model where the values correspond to specific compositional elements2.

Protective Mechanisms of Dietary Fibers in Nutritional Carcinogenesis

Abstract: Fibers in foods are complex carbohydrates. There are several types of fiber, but, for the purpose of mechanistic insight into their mode of protective action in carcinogenesis, classification into two broad types, soluble and insoluble fibers, is warranted. Soluble fibers are present in fruits, vegetables, and certain grains like oats. This type of fiber undergoes metabolism in the small intestine and especially in the large intestine through bacterial enzymes, converting it to products that increase stool size only moderately. But, they have appreciable effects in modifying the metabolism of colon carcinogens like azoxymethane to yield detoxified products and, thus, reducing colon carcinogenesis. In contrast, insoluble fibers present in sizeable amounts in bran cereals, like wheat or rice, are not significantly metabolized by enzymes in the intestinal flora. Such fibers increase stool size substantially through several mechanisms, including higher water retention. The larger bulk dilutes carcinogens, especially tumor promoters such as secondary bile acids, resulting in lower risk of colon cancer in animals and in humans. Evidence in animal models and in humans also indicates that fiber may lower the risk of breast cancer, possibly via an endocrine mechanism. Based on these concepts, increased intake of total fiber, but especially of wheat bran cereal fiber, to yield a daily stool in adults of about 200 grams can significantly reduce the risk of colon cancer and, to a lesser but definite extent, of breast cancer. Thus, adequate fiber intake from cereals, fruits, and vegetables can help prevent important types of human cancer.

Multicomponent Models in Body Composition Research: Opportunities and Pitfalls

Abstract: The opportunities for multicomponent models have increased recently because of the development of new methodologies including dual energy X-ray absorptiometry (DXA), total body electrical conductivity, neutron activation analysis and bioelectric impedance along with the traditional measures of body water, potassium and density. The need for valid multicomponent body composition approaches has arisen because of the failure of the two-component model, i.e., fat and fat-free body (FFB), to yield accurate estimates of body composition both within and among various populations. Without valid two-component approaches, the field of body composition has lacked a criterion method by which to validate new body composition methods. With the development of valid and precise multicomponent approaches, reference fat-free body compositions can be established for various populations, changes in body composition with growth and aging can be more accurately assessed, and the effect of dietary and exercise programs can be quantified on various body components. The pitfalls of various multicomponent body composition approaches now in use arise from theoretical, methodological and statistical considerations. It is the purpose of this paper to review present limitations in various multicomponent body composition approaches and to develop a set of guidelines to foster valid multicomponent systems.

Recent Results in Preclinical and Clinical Drug Development of Chemopreventive Agents at the National Cancer Institute

Abstract: A primary goal of the Chemoprevention Program of the Division of Cancer Prevention and Control (DCPC) at the National Cancer Institute (NCI) is the development of safe and effective chemopreventive agents This NCI effort is organized as an applied drug development science program, with clinical trials as the final endpoint The objective of this paper is to establish a perspective for the applied research in drug development that is sponsored by the Chemoprevention Program, and to present recent results and progress in the development of the most promising chemopreventive agents

Identification of Natural Antimutagens with Modulating Effects on DNA Repair

Abstract: The results of a study of bioantimutagenesis, with emphasis on natural antimutagens from plant extracts with modulating effects on DNA repair in Escherichia coli bacteria are presented in this chapter. Comparative screening for spontaneous or induced mutagenesis, as well as expression of the SOS gene, sfiA was accomplished.

In vivo measurements of lead in bone using a 109Cd 'spot' source.

Abstract: The principles of X-ray fluorescence (XRF) have been described elsewhere1. The XRF technique described here uses the 88.035 keV γ-rays from 109Cd which fluoresce the K shell X-rays of lead and a backscatter geometry is adopted. This technique was developed at the University of Birmingham, England2. In addition to the one described here, further measurement systems are under development3.

DXA Measurements of Fat and Bone Mineral Density in Relation to Depth and Adiposity

Abstract: Significant effects of depth and adiposity on measurements of fat have been observed, which if also true in-vivo, have important implications for studies at the extremes of body composition, or for longitudinal measurements in subjects who show large changes in tissue thickness. Measurements of BMD under similar circumstances appear to be more robust. However, assessments of the absolute accuracy of DXA measurements await comparison with chemical analysis of human or animal cadavers.

Whole body potassium measurements independent of body size.

Abstract: The measurement of total body potassium (TBK) has long been recognized as an accurate index of the body’s cell mass, that is, the metabolically active tissues of the body. Whole-body counters, therefore, have been used extensively to monitor TBK in a wide range of healthy and diseased populations. Thus, we undertook the task of designing a counter that could accurately measure body potassium in a range of body sizes from a very-low-birth-weight (VLBW) infant to an obese adult. A strong emphasis was placed on the in vivo measurement of TBK in healthy infants, children, and teenagers. We describe the different counting configurations and performance characteristics of the Children’s Nutrition Research Center (CNRC) whole-body counter.

The Companionship of Lean and Fat

Abstract: This statement is as true today as when it was uttered years ago; indeed, approximation is the hallmark of all body composition techniques, and it is this basic fault together with the innate variability and fluctuations of biological systems which render our results less exact than desired.

Inhibition of Nitrosation

Abstract: Humans are exposed through ingestion or inhalation to preformed N-nitroso compounds (NOC) in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages and bacterial strains isolated from human infections can enzymatically produce nitrosating agents and NOC from precursors at neutral pH. As a consequence, endogenous nitrosation may occur at various sites of the body, such as the oral cavity, stomach, urinary bladder, and at other sites of infection or inflammation. Numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC. Such inhibitors include vitamins C and E, certain phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and, thus, act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins, and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. This article briefly reviews (a) the chemistry of NOC formation and inhibition; (b) the studies in experimental animals that showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic, and carcinogenic effects; (c) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified; and (d) the possible contribution of nitrosation inhibitors to human cancer prevention.

Oxidants and Mitogenesis as Causes of Mutation and Cancer: The Influence of Diet

Abstract: A very high level oxidative damage to DNA occurs during normal metabolism. In each rat cell, the steady-state level of this damage is estimated to be about 10 6 oxidative adducts, and about 10 5 new adducts are formed daily. This endogenous DNA damage appears to be a major contributor to cancer and aging. The oxidative damage rate in mammalian species with a high metabolic rate, short life span, and high age-specific cancer rate such as in rats is much higher than the rate in humans, long-lived mammals with a lower metabolic rate, and a lower age-specific cancer rate. It is argued that deficiency of micronutrients, that protect against oxidative DNA damage, is a major contributor to human cancer.

Assessment of changes in extra-cellular water and total body water using multi-frequency bio-electrical impedance.

Abstract: Multifrequency bioelectrical impedance is a new approach in impedance methodology. Theoretically an alternating current with a low frequency is not able to penetrate the cell membrane because of the high capacitive resistance of the membrane. Consequently the measured impedance at low frequency is a measure of extracellular water (ECW) only. At high frequency the capacitive resistance diminishes. Hence the measured impedance at high frequency will be related to total body water (TBW). Aim of this study was to develop prediction formulas for ECW and TBW at different frequencies and to check the validity of these formulas in the assessment of body water compartments and changes in body water compartments.

Body composition studies in Prader-Willi syndrome: effects of growth hormone therapy.

Abstract: Prader-Willi Syndrome (PWS) is characterized by infantile failure to thrive, progressive childhood obesity, hypotonia, hypogonadism, mental retardation and phenotypic abnormalities including short stature. Abnormalities of chromosome 15 can now be identified in virtually all cases1. The pathogenesis of PWS is not known, although the phenotype suggests that there may be an abnormality in substrate utilization leading to an absolute deficit of lean mass and increased fat mass. Hypothalamic and pituitary abnormalities have also been postulated2,3. However, studies of body composition, nutrient utilization, and hormone status in PWS are limited. We report initial results from a detailed investigation of body composition and growth hormone (GH) treatment in PWS.

Mechanisms of antimutagenesis and anticarcinogenesis: role in primary prevention.

Abstract: Figure 1 reports the possible intervention strategies against cancer, as related to the multistep carcinogenesis process and to growth of the neoplastic mass. Similar concepts may hold true for other mutation-related conditions and, in general, for those chronico-degenerative diseases having a multifactorial origin, a multistep pathogenesis, and a long latency period. Keeping in mind that the neoplastic mass is of monoclonal origin, and assuming a regular doubling of the population of neoplastic cells, 30 cell divisions will be needed to form a mass of 10 9 cells from a single cell undergoing initiation. Very approximately, this mass may weigh 1 g. At this stage, depending on many variability factors, it may be possible to apply secondary prevention, involving early detection and therapy. Otherwise, in 3.25 further divisions the mass will be composed of 10 10 cells and weigh 10 g. At this stage, which may already involve invasion and spread of metastases, the disease will become clinically manifest and will be treated with the most suitable therapeutic protocol. This intervention will be followed by tertiary prevention, which aims at avoiding relapses, complications, metastases, and second primitive tumors. In the absence of any medical intervention, in 10 cell divisions only (i.e., from the 30th to the 40th division), the neoplastic mass will grow from 1 g to as much as 1 kg (20). Although this computer-drawn growth is a mathematical oversimplification and does not take into account possible natural regressions of the disease, it gives an idea of the paramount importance of early detection and explains the difficulties that are encountered in cancer therapy when the disease becomes clinically manifest.

CT-Determined Body Composition Changes with Recombinant Human Growth Hormone Treatment to Adults with Growth Hormone Deficiency

Abstract: Growth hormone (GH) is secreted in children as well as in adults. Several studies show an important role of GH in adults. Recent trials with recombinant human growth hormone (rhGH) have demonstrated profound effects on body composition, metabolism and quality of life.1,2 Salomon et al1 showed that adults with growth hormone deficiency had decreased lean body mass and increased body fat. Treatment with rhGH for six months increased lean body mass (LBM) and reduced body fat. Jorgensen et al2 have shown that four months of GH substitution to GH-deficient adults had a normalizing effect on several physiological variables, which were out of normal range before treatment.

Preventive Effect of Magnesium Hydroxide on Carcinogen-Induced Large Bowel Carcinogenesis in Rats

Abstract: Preventive effect of magnesium hydroxide on carcinogen-induced, large bowel carcinogenesis was examined in three experiments using F344 rats. Experiment I: Rats received dietary administration of magnesium hydroxide at concentrations of 500 or 1,000 ppm after treatment with methylazoxymethanol (MAM) acetate (25 mg/kg, 3 times). These rats had a lower incidence of large bowel neoplasms than animals given MAM acetate alone. Reduction of the tumor incidence was especially significant at a dose of 500 ppm. Experiment II: Rats given magnesium hydroxide (250, 500, or 1,000 ppm) together with 1,2-dimethylhydrazine (DMH) (20 mg/kg, 10 times) showed a lower multiplicity of large bowel tumors than those given DMH alone. Experiment III: The labeling indices of the cryptal cells of the large bowel (cecum or proximal colon or distal colon) or rates given magnesium hydroxide for 4, 6, or 8 weeks after treatment with MAM acetate (25 mg/kg, 3 times) were smaller than those of animals given MAM acetate alone, indicating that magnesium hydroxide suppressed, carcinogen-induced epithelial cell (large bowel) proliferation. The results of the three experiments suggest that magnesium, one of the essential metals, is a promising chemopreventive agent in humans.

Effects of meal and its electrolytes on bioelectrical impedance.

Abstract: Bioelectrical impedance analysis (BIA) is a simple, reproducible and indirectly validated technique for the assessment of body composition1–3 It is based on the physical principle that the impedance (or conductivity) of a geometrical system is related to the conductor length and configuration, its cross-sectional area, and signal frequency4 Assuming a constant conductor configuration and using a fixed signal, the impedance becomes a function of conductor (body) volume The conductive pathway is directly related to the water content of the body Therefore, the conductivity is minimal in the less hydrated fat tissue and far greater in the fat—free body mass which contains virtually all the water and conducting electrolytes In other words, the BIA is an index of total body water and evidently affected by the alterations in the concentration of conductive electrolytes5

Five-Level Model: Reconstruction of Body Weight at Atomic, Molecular, Cellular, and Tissue-System Levels from Neutron Activation Analysis

Abstract: Ratio-based methods, which estimate unknown components based on the ratio between unknown and known components, play an increasingly important role in body composition methodology. Presently available ratio-based methods are usually simple and involve calculation of an unknown component from one known component. Moreover, there are no methods for some components such as total body oxygen and fat cells.

Mechanisms of Inhibition of Tumor Progression

Abstract: Experimental and epidemiologic studies have demonstrated that carcinogenesis is a multistage process that can be divided into three major stages: initiation, promotion, and progression (22). Progression encompasses the changes by which a tumor evolves from a contained, differentiated lesion of uncoordinated growth into a rapidly growing, invasive lesion with potential to spread to other areas of the body. This change is also associated with conversion from an easily removed growth to one requiring extensive therapy with variable rates of recovery and, thus, constitutes a phase of cancer development of critical clinical relevance. Nonetheless, this stage of carcinogenesis has remained the least understood.

Total body fat and its distribution during human reproduction as assessed by magnetic resonance imaging.

Abstract: Changes in the amount as well as in the distribution of fat in the female body are known to occur during human reproduction. Knowledge about the magnitude of these changes as well as their biological basis is a prerequisite for adequate recommendations of energy for pregnant and lactating women. Estimates of total body fat (TBF) obtained so far in pregnant and lactating women, have to be interpreted with caution because the methods used are based on assumptions possibly invalid during reproduction1. A method for assessing TBF and its distribution, based on magnetic resonance imaging (MRI-method), has therefore been developed and applied in a longitudinal study of women throughout a reproductive cycle (Sohlstrom et al, data to be published).

Effect of Antioxidant Supplementation in an Elderly Population

Abstract: According to some contemporary theories, the aging process in humans may be the result of the accumulation of unsuccessfully repaired genetic damage. The critical changes determining cell senescence are most probably the changes that take place in macromolecules such as DNA and RNA, enzymes, and structural parts of biomembranes--lipids and proteins.

Chemoprotection by inducers of electrophile detoxication enzymes.

Abstract: Many potential strategies exist for chemical protection against carcinogenesis Multiple stages of carcinogenesis, including initiation, promotion, and progression, can serve as targets for different types of interventions [see reviews by Wattenberg (32); De Flora and Ramel (10)] However, in the majority of experimental systems, protection has been achieved by administering the chemoprotective agent prior to and/or concurrent with the exposure to carcinogen Given this temporal relationship between administration of anticarcinogen and carcinogen, it seems likely that these agents act principally by affecting the metabolism and disposition of carcinogens, thereby altering events critical to the initiation of carcinogenesis Using this experimental approach, it has been possible to document protection against a diverse array of chemical carcinogens acting at many different target organ sites Important classes of chemoprotectors that modulate the metabolic processing of carcinogens include phenolic antioxidants, indoles, organic isothiocyanates, coumarins, flavones, allyl sulfides, dithiocarbamates, and dithiolethiones

Dietary inhibitors against mutagenesis and carcinogenesis.

Abstract: It has become increasingly clear that mutagenesis plays a central role in the multiple steps of carcinogenesis (42,51,155). Finding inhibitors in the diet and studying the mechanisms of their actions are important in providing humans a preventive measure against cancer (170). Mutagenesis- and carcinogenesis-inhibitors have been extensively studied, although the mechanisms of the inhibitions are, in many cases, not well understood.

In vivo X-ray fluorescence analysis with applications to platinum, gold and mercury in man--experiments, improvements, and patient measurements.

Abstract: The presented in vivo X-ray fluorescence (XRF) analysis1 system is used for the determination of platinum (Pt), gold (Au) and mercury (Hg) in man. Such measurements are of interest in connection with surveillance of occupationally exposed workers (Hg) as well as in medical research regarding patients treated with substances containing heavy metals (Pt and Au). To be able to make these measurements with a high degree of accuracy it is important to optimize the measuring conditions as the heavy metal concentration is low. This paper describes a number of tests and improvements made using an in vivo XRF analysis system. In addition, measurements of Au in 27 gold-salt-treated rheumatoid arthritis patients and of Pt in two cisplatin-treated tumor patients were performed. The aim of the Au measurements was to investigate whether Au could be detected in kidney and liver. The Pt measurements were made to study the uptake of cisplatin in vivo in tumor tissue, normal tissue and risk organs, e.g. kidneys. Parts of this study have been presented elsewhere.2–4

Determination of anatomical skeletal muscle mass by whole body nuclear magnetic resonance.

Abstract: Quantitation of skeletal muscle mass is of physiological relevance and an important part of the nutritional assessment. However, no definitive methods are available for quantifying whole body skeletal muscle mass in vivo. Routine methods for approximating muscle mass currently include estimation from body mass (b.m.)1 or fat free mass (FFM)1, anthropometrics2, and the creatinine approach3. Nuclear magnetic resonance (NMR) has been used to quantitate total adipose tissue in man4; however its suitability for whole body skeletal muscle mass determination is not well investigated. We therefore evaluated the direct measurement of anatomical skeletal muscle mass by whole body NMR in comparison with routine methods, as well as its possible impact on the estimation of muscle glucose uptake as measured by positron-emission tomography (PET) in combination with the glucose clamp technique.

Aqueous and Mineral Fractions of the Fat-Free Body and Their Relation to Body Fat Estimates in Men and Women Aged 49–82 Years

Abstract: Due to age-related decreases in bone minera11,2 and total body protein3 coupled with a possible increase in the hydration of the fat-free mass (1,1-M)4, it is likely that, on average, the density of the FFM is lower in older relative to younger adults. Other investigators have speculated that the density of the FFM may become more variable with advancing age5,6. In either case, erroneous estimates of body fat percentage (%Fat) will result when traditional two-component (2C: fat and fat-free) models7 are used in older adults. More complex four component (4C: fat, water, mineral and fat-free residual) models3,5,8 may provide more valid substitutes for the 2C model7 in older adults.

Body Composition Analysis by Dual Energy X-Ray Absorptiometry Compared to Chemical Analysis of Fat, Lean and Bone Mass in Small Piglets

Abstract: The influence of nutrient intake on body composition in growing low birthweight infants is essential knowledge in order to optimize nutritional management for the support of growth and development. Until recently, indirect methods of measuring body composition were inappropriate; but the latest generation of whole body densitometers, dual-energy X-ray absorptiometry (DXA) may be a useful tool for this age group. The application of DXA for quantitative assessment of fat, lean and bone mass should provide measures with precision and accuracy while being safe and noninvasive for use in infants and small children. Our objective was to establish the precision and accuracy of DXA measurements of whole body bone mineral content (BMC), fat and lean tissue in young piglets which are similar in body composition to infants1,2.

Body Composition Measurements During Pregnancy

Abstract: Body composition is of particular interest during pregnancy, because the additional calorie increment estimated as necessary during pregnancy (about 250–300 kcal/day) is determined to a large extent by the amount of additional fat thought to be stored. Weight gain recommendations for pregnancy also assume certain fat changes occur during normal pregnancy.

Comparison of Proximal and Distal Placements of Electrodes to Assess Human Body Composition by Bioelectrical Impedance

Abstract: The use of bioelectrical impedance variables, including resistance (R), to estimate body composition of healthy individuals is based on the predominant conduction of an applied electrical current by the components of the fat-free body, principally water and electrolytes.1 To date, attempts to derive and validate models for assessment of body composition, estimation of fat-free mass (FFM) and calculation of percent body fat (%BF) have yielded reasonable success.2 Two factors that affect R measurements, however, may explain some of the variability in the success of investigators in using bioelectrical impedance analysis (BIA) to predict human body composition.

Extracellular Interception of Mutagens

Abstract: Extracellular interception of mutagens by excreted enzymes or by chemical agents that react with or bind to formed mutagens provides an important means of defense against chemical mutagens/carcinogens. Kada and Shimoi (25) have classified molecules that function in this manner as “desmutagens,” and many of them are natural cellular metabolites (23). Among the specific mechanisms that such agents may employ are: prevention of the activation of “promutagens” to mutagens; stimulation of enzymes (e.g., glutathione-S-transferase) that catalyze the binding/inactivation of damaging electrophiles; direct binding and concomitant inactivation of promutagens or mutagens; interference with uptake of mutagens into cells; etc. De Flora and Ramel (11) have provided an excellent discussion of the mechanisms of these agents and a proposed classification scheme. Drawing on work from our own laboratories and other recent examples in the literature, several examples of mechanistic approaches to these studies using natural plant-derived materials, e.g., humic acid, Glycyrrhha glabra extract, glutathione, and bioflavonoids, are also described. Antioxidants and agents that conjugate electrophiles will be among the modes of action described for obtaining the goal of intercepting mutagens/carcinogens.