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The Possibility of Continuously Measuring Energy Metabolism

The small body size of insects offers the opportunity of continuously monitoring the total energy metabolism of a whole population over their total life span. This results in a ''metabolic picture.'' One can then test the influence of different treatments (e.g., temperature, light program, drugs, mating, virginity) on the energy consumption. We performed such measurements with Phormia using an infrared CO2 monitoring system (URAS). Due to the restriction on carbohydrates as energy-providing substrate, the CO2 output equals the O2 input and therefore gives a true picture of energy metabolism. Thirty-five flies were placed in a respiration chamber and fed in the usual manner with sugar and water. The relatively big volume of the chamber allows unrestricted flying and walking activity. Figure 21.4 shows an example of such a measurement. The CO2 production per 30 min was calculated from the continuous monitoring. Males and females exhibit a very different energy profile. In both sexes,...

Energy Metabolism The Critical Role of Mitochondrial Function Decay

Cerebral energy metabolism in aging has been investigated in animal models and human beings by measuring different parameters, such as cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) or oxygen (CMRO2). Noninvasive techniques have been developed during the past decades beginning in the early 1960s to measure these important parameters. Positron emission tomography (PET) is one of these currently used methods and is based on principles of computerized tomography and radioisotope imaging. Specifically in emission tomography, the image is generated by differences in the distribution in the tissue of injected or inhaled isotopes that are constituents of important biological molecules. The radiation emitted by the isotopes can be detected, analyzed, and used by a computer to visualize the zones where a specific biological molecule is metabolized. In PET, the isotopes of elements that decay after minutes or hours are normally used and emit positrons (positive...

Endocrine and metabolic response to surgery

Surgery represents a major stress, the metabolic effects of which are more pronounced in infants than adults. In response to surgery, there is an increase in plasma concentrations of adrenaline, noradrenaline, insulin, glucagon, glucose, lactate, pyruvate and alanine. The response is directly proportional to the severity of surgical stress. Cortisol and prolactin levels are also increased postoperatively. Cytokines which mediate the host response to injury, are also implicated. Plasma levels of interleukin-6 and interleukin-8 are

Functions Of Copper And Regulation Of Copper Metabolism

Most of the copper transporters and chaperones already described, that have been cloned and investigated so far, are listed in Table 3, along with a brief summary of what occurs when they are defective or knocked out (if this is known). For most of these, more detailed descriptions of their functions have already been provided. The fact that copper is an essential element, however, is not because of its carriers and transporters but because of specific copper-dependent enzymes (and perhaps also other factors) that are crucial for life and for human metabolism and function. A list of the known copper-containing enzymes proteins in humans and mammals is given in Table 4, along with brief descriptions of their functions. This is in addition to the list of plasma copper constituents given in Table 2. Ceruloplasmin is included in Tables 2-4, because it plays a variety of roles in addition to that of delivering copper via the blood. Further descriptions of the most interesting aspects of...

Feeding ecology and diet

Primate species exhibit a wide range of diets, although most of them include at least some fruits in their food intake. If there is a typical dietary category for primates generally, it is surely fruit consumption, as this is found from the smallest to the largest species. Although most primates eat at least some fruits, primates can be classified into three main dietary categories representing at least 50 of food intake (1) insectivores, feeding mainly on arthropods (e.g., tarsiers) (2) frugivores, feeding mainly on fruits (e.g., most forest-living monkeys) (3) folivores, feeding mainly on leaves (e.g., leaf-monkeys). There is a general trend among primates for the diet to shift progressively from insectivory through frugivory to folivory as body size increases. This is understandable because small-bodied mammals have relatively high-energy requirements per unit body weight and must eat foods with a rich, easily available energy content. Large-bodied mammals have relatively low...

Dimensions of Assessment

Duration is the total amount of time spent (e.g., in minutes, hours) performing the physical activity. Intensity reflects the amount of energy expended while performing the physical activity of interest and is typically expressed in metabolic equivalents (METs), a ratio of the metabolic rate during physical activity relative to the resting metabolic rate (3.5 ml O2 kg min). A MET value of 1.0 is roughly equivalent to the energy expenditure at rest hence, if an individual engages in physical activity equivalent to a MET level of 10, they would expending 10 times the energy compared to their energy expenditure in a resting state. A compendium of physical activities and MET intensities can be used to estimate total energy expenditure (Ainsworth et al, 2000).

Exercise Treadmill Testing

In the Duke-Wake Forest protocol (Blumenthal et al, 1988), workloads are increased at the rate of 1 MET (3.5 ml O2 kg min) per minute minute 1,2.0 mph, 0 grade minute 2,2.5 mph, 0 grade minute 3, 2.5 mph, 2.0 grade and so on. The advantage of this protocol is that workload is increased in multiples of the resting metabolic rate, as opposed to more arbitrarily defined increments of speed and grade.

Diseasespecific diets

Research is being undertaken on the use of nutritional substrates or supplements such as fish oils, arginine, glutam-ine and nucleotides, designed to modify or modulate the immune and metabolic response to stress. As yet the clinical value of such diets is unclear and recommendations cannot yet be given on their use.

Parkinsonism In Young Adults

These patients have a long-standing hemiatrophy of the body and develop a progressive bradykinesia and dystonic movements around the age of 40 (133). Ipsilateral corticospinal tract signs may be found, which are not a feature of PD. Neuroimaging reveals brain asymmetry with atrophy of the contralateral hemisphere with compensatory ventricular dilatation. Regional cerebral metabolic rates are diminished in the hemisphere contralateral to the clinical hemiatrophy in the putamen and the medial frontal cortex, whereas in PD the regional cerebral metabolic rates are normal or increased contralateral to the clinically affected side (134).

Heart Rate Monitoring

Method, heart rate and oxygen consumption are monitored at different exercise intensities and different postures (i.e., sitting, supine, and standing). Basal metabolic rate is also estimated for each subject. These data are used to construct a calibration curve to estimate energy expenditure (Freedson and Miller, 2000). The FLEX heart rate is the threshold heart rate used to differentiate between resting and exercise heart rate (Livingstone, 1997). Satisfactory estimates of total energy expenditure have been reported using this method (Ceesay et al, 1989 Spurr etal, 1988).

Use of Human Breast Cancer Cell Lines to Detect Specific Receptor Induced Proteins

The two progestins were also similarly active, but at higher concentrations, inducing a specific response to an androgen receptor such as that of a 43-kD androgen induced secreted protein (16), which has been identified as the glycoprotein (19). The weaker activity of progesterone on the cell lines was probably due to its high metabolism of inactive products, while R5020 has been shown to be more stable. Both MPA and R5020 are pregnane derivatives, and, supposedly, both are less androgenic than 19 nor-testosterone progestins.

Nitrogen And Carbon Dioxide

When comparing different inert gases, i.e. gases not taking part in human metabolism, we can state a parallelism between relative narcotic potency and solubility in lipids. Provided the relative narcotic effect of nitrogen is 1, other gases may ranked according to their relative narcotic potency (see table 1.3-3). Solubility of gases in lipids shows that gases with a higher narcotic potency also have a higher solubility in lipids compared with less

Effect of hyperoxia on VO2 under pathological conditions

Cerebral oxygen consumption has been investigated in 37 severely brain injured patients40. A maximum of seven treatments per patient had been applied at 151.9kPa (1.5ata) for 60 minutes. Patients were divided into the three categories of reduced, normal or increased pre-session cerebral blood flow. Cerebral blood flow, arterial venous oxygen content difference, cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid lactate and intracranial pressure values were assessed one hour before, and one and six hours after HBO therapy. CMRO2 increased and lactate levels decreased after treatment, which suggested an improvement of aerobic

Visualization of Disease Progress

In nuclear medicine, several kinds of organ function can be measured simultaneously with various radiopharmaceuticals under different conditions. This gives us useful information about the stage of disease progress if the relationship between various parameters such as metabolism, blood flow, and hemodynamics can be elucidated. Toyama et al. 116 investigated the use of agglomera-tive hierarchical and K -means clustering methods to study regional vasodila-tive and vascoconstrictive reactivity and oxygen metabolism before and after revascularization surgery in chronic occlusive cerebrovascular disease. By clustering a four-variable correlation map, whose pixel values on the X, Y, Z, and T axes represent, respectively, the resting cerebral blood flow, the hyperventila-tory response, the acetazolamide response, and regional oxygen metabolic rate, anatomically and pathophysiologically different areas can be identified showing the involvement of certain areas with varying degrees of...

Segmental Duplications And Genomic Variation

The role of duplications as mediators of recurrent genomic disorders is well established, with more than 25 separate syndromes now recognized. However, there is a growing body of evidence that suggests segmental duplications may also play a significant role in normal variation. The existence of large genomic polymorphisms, originally termed heteromorphisms or euchromatic variants, has been recognized since the advent of high-resolution cytogenetic banding techniques (69) (summarized at anomaly 20register ). Using more targeted molecular analyses, and more recently with the advent of high-throughput methodologies such as array CGH, large numbers of submicro-scopic deletion duplication and inversion polymorphisms have now been documented (70,71). As with the recurrent genomic disorders, many of these similarly seem to be mediated by the presence of flanking duplicated sequences (71,72) (summarized in Table 1). In some instances these polymorphisms are associated with extreme divergences...

Sympathoadrenal system

The system eventually becomes hyperdynamic, with increased cardiac output in order to satisfy the demands of increased metabolism, changes in the thermoregulatory system and wound healing. The magnitude of the changes in metabolic rate varies depending on the injury. Treatment with aggressive fluid resuscitation and inotropic support may include additional catecholamines to maintain the body's response to injury. The induced hypermetabolic state peaks at 5-10 days after the injury at the height of inflammation, and returns to normal as wounds heal.

Living in a safe predictable world

Unusually long lifespans (an age of over 25 years has been recorded in the naked mole-rat in captivity, and there is an African mole-rat, Cryptomys anselli, that is at least 22 years old and is still breeding). On the proximate level, slow growth is surely correlated with low metabolic rates. However, the effect of phylogeny is very strong and phylogenetic relationships can best explain the length of pregnancy and many other parameters of life histories, such as mating behavior and mating system, as well as social systems.

The Chronological Aging Assay

Longo, 2003 MacLean et al., 2001), and many others can be imagined. The most commonly utilized variation involves growing cells into stationary phase in chemically defined media with glucose as the carbon source and maintaining the cells in culture for a period of several weeks (Fabrizio and Longo, 2003). An alternative method, in which cells are grown to stationary phase in rich media and then transferred to water, has also been described. A major difference between these two methods is the metabolic state of the cells in the quiescent state cells aged in synthetic media maintain a high metabolic rate, whereas cells transferred to water from rich media enter a so-called hypometabolic state (Fabrizio and Longo, 2003). Survival time is greatly enhanced for cells maintained in water relative to cells maintained in synthetic medial. In general, it has been observed that mutations altering chronological life span in one of these assays have the same effect on life span as measured by the...

Chronological Life Span Survival In The Postdiauxic And Stationary Phases

Microorganisms have evolved to survive under adverse conditions, such as starvation, that are commonly encountered in the wild. In fact, most microorganisms are estimated to survive in a low-metabolism stationary phase under nutrient-depleted conditions (Werner-Washburne et al., 1996). In the wild, yeast organisms are likely to exit stationary phase only during the rare periods when all the nutrients required for growth become available. For this reason we perform most of our experiments in either a medium containing a limited amount of nutrients synthetic dextrose complete (SDC) or in water. Wild-type DBY746 or SP1 yeast grown in SDC medium survive 5 to 6 days while maintaining high metabolic rates for the majority of the life span (Figure 19.1). When yeast grown in SDC are switched to water between days 1 and 5, metabolic rates decrease and survival is extended (Fabrizio et al., 2004a). However, since long-lived mutants isolated by incubation in SDC also live longer when incubated...

Life Span Characteristics and Factors Which Are Responsible for Modifying an Insects Life Span

The ambient temperature is therefore a key life-span modifying factor. It is easy to manipulate the metabolic rate simply by changing ambient temperature. The mentioned work of Loeb and Northrop used this regimen as an experimental tool. The light regime also acts as a prominent abiotic stimulus together with the temperature. Both factors are essential in habitats with distinctive seasons they determine in many species whether phases of dormancy occur or not. A phase of low metabolism can be induced experimentally by changing the photoperiod from long day (16 8) to short day (8 16). This treatment evidently interrupts the aging process (see below).

HAART lipodystrophy syndrome and cardiovascular risk

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the metabolic syndrome in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential therapy-related increased risk of myocardial infarction in HIV patients. These fears are further sustained by reports of arterial hypertension on HAART, a high rate of smoking among HIV patients and increased levels of tissue plasmino-gen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with lipodystrophy. Although many of the, mainly retrospective, studies dealing with this issue are inconclusive, data from a large international study (D A D study) provide evidence for an increased...

Interval Timing And Foraging

Warm-blooded vertebrates such as small mammals and birds have relatively high metabolic rates, the maintenance of which requires large quantities of food on a regular basis. This need is assumed to have imposed a strong selective pressure to produce efficient foraging behavior. Birds in particular have been at the forefront of studies of optimal foraging because the high energetic demands of flight have meant that birds need to ingest particularly large quantities of food of high nutritive value. A small bird may need to eat its body weight in food per day. A blue tit (Parus caeruleus) weighing 11 g needs 11 kcal per day in winter, which is equivalent to around 300 small insects, and a rufous hummingbird (Selasphorus rufus) weighing 3.5 g will visit a nectar feeder approximately every 10 to 15 min from dawn until dusk. These high rates of foraging coupled with the fact that most birds forage only during the hours of daylight make birds attractive subjects for studies of foraging...

Alexander M Spence David A Mankoff Mark Muzi and Kristin Swanson

This chapter reviews nuclear imaging of gliomas, both high- and low-grade, with emphasis on results from positron emission tomography (PET) with F-18 -2-fluoro-2-deoxyglucose (FDG) for assessing energy metabolism. There are many additional advances beyond FDG-PET that are very exciting and potentially applicable in the management of gliomas. Biosynthesis in tumors occurs along several important broad fronts for DNA, proteins, and membrane lipids. Molecular imaging of these pathways is coming to the foreground. Hypoxia, a significant resistance mechanism that compromises the efficacy of radiotherapy and chemotherapy, can now be regionally quantified in vivo with PET. In the near future it is likely that the presence of mutant receptors, apoptosis, and angiogenesis will also be measurable with PET and new tracers.

Comments On Physiology

The appearance of male and female flies is described elsewhere see the Recommended Resources section. Like the mammals for which it often serves as a proxy, Drosophila has a nervous system, hormonal system, and circulatory system. However it lacks several systems present in mammals, and many shared systems function somewhat differently. First, as a poikilotherm, temperature has a direct effect on metabolic rate, and lifespan of the flies can be significantly extended when they are kept at lower temperatures (see below). Because the adult fly consists mostly of postmitotic cells, issues such as replicative senescence, cell proliferation in aging, and cancer development have not been considered in flies however, these factors may be important in higher organisms that have many mitotic cells.

Neurophysiological Factors

As discussed in Chapter 3, organic brain disorders can have a pronounced effect on behavior and abilities. This is particularly evident in Alzheimer's disease, a disorder that afflicts approximately 20 of individuals in the 75- to 84-year age range and about 47 of those over 85 (Evans et al., 1989). An even greater percentage of older Americans suffer from hypertension, another disorder that is associated with reduced intellectual functioning (Hertzog, Schaie, & Gribbin, 1978 Sands & Meredith, 1992) and which can lead to cardiovascular disease and stroke. By interfering with the oxygen flow to the brain, a major stroke can affect not only intellectual abilities but also speaking, walking, and other skills. The brain's blood supply can also be temporarily reduced by emphysema, acute infection, poor nutrition, injuries, and surgery. The loss of neuronal tissue, changes in metabolic rate, and a decline in blood circulation also have depressing effects on cognitive functioning....

Physiological And Biochemical Approaches

Physiological measures are important because they can provide insight into the nature of aging processes, which may not be apparent from the age-at-death measure that is used in demographic studies. A number of different types of behavioral assays such as learning and memory have been established (Connolly and Tully, 1998). Also there are other measures that are relevant to aging number of eggs laid, negative geotaxis, immune function (DeVeale et al., 2004), heart function (Wessells et al., 2004), and circadian rhythm (Driver, 2000). Metabolic rate can be assayed by respirometry calorimetry (Hulbert et al., 2004), and stress resistance can be tested in various forms, including hydrogen peroxide, paraquat feeding, cold, starvation, and desiccation.

Assessing Response to Therapy

These Kaplan Meier plots show survival results for 14 patients scanned with FDG both before and after RT. The patients were ranked from greatest to least value of the ratio of post-RT MRFDG over the pre-RT MRFDG and then split in two groups, higher 50 vs lower 50 . Survival was compared between the two groups. Two patients still alive were censored. The graphs show that an increase in metabolic rate from before to after RT correlates with longer survival. Fig. 4. These Kaplan Meier plots show survival results for 14 patients scanned with FDG both before and after RT. The patients were ranked from greatest to least value of the ratio of post-RT MRFDG over the pre-RT MRFDG and then split in two groups, higher 50 vs lower 50 . Survival was compared between the two groups. Two patients still alive were censored. The graphs show that an increase in metabolic rate from before to after RT correlates with longer survival. Another way to measure response to therapy is to assess...

Oxygen Metabolism And Blood Flow [o15o2 [o15h2o [o15co

Oxygen metabolic rate (MRO2), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in malignant gliomas have all been examined by several groups (2,42-46). Among these studies there is consistency in showing that oxygen utilization is low relative to normal cortex despite an adequate supply of oxygen, at least macroscopically (i.e., there are adequate blood flow and blood oxygen levels to meet the metabolic demands of the tumors). Wise et al. in particular noted that both MRO2 and OEF tend to be lower in malignant gliomas suggesting the tissue is not macroscopically ischemic (46).

Physiological Signatures And Patterns Of Lifespan

Metabolic Rate (MR) MR is one physiological factor that may underlie the temporal, caste-associated mortality rates of honeybee workers. Forager MR is significantly higher than the MR of hive bees (for a discussion see Suarez et al., 1996), and the MR of a foraging bee constitutes one of the highest known mass-specific aerobe MRs among animals (approximately 3-fold higher than hummingbird flight muscle). Such intense activity is a major source of mechanical senescence in insects and causes mortality to increase as a function of age (reviewed by Finch, 1990). In accordance with their longevity, diutinus bees periodically exhibit low MRs compared to hive bees and thus also relative to foragers (Crailsheim, 1986 Nerum and Buelens, 1997). The MR of diutinus workers can fall to half the MR of hive bees. Elevated MR causes an increase in the release of free radicals that can induce oxidative impairment (reviewed by Jazwinski, 1996), which has led to the suggestion that oxidative stress is a...

Oral diseases and cariogenicity

Dental cavity formation results from a complex series of interactions occurring on the tooth enamel surface inside of the plaque biofilm. Generally, cariogenic bacteria produce organic acids that demineralize the calcified surface (Fig. 7.4). Once cavitation has begun, the tooth is continually under siege due to the different metabolic rates of cariogenic bacteria. Organic acid penetrates through the plaque biofilm to the tooth's enamel surface and begins diffusing into hydroxyapatite through water-filled interprismatic spaces. Loss of apatite crystals in the enamel is demineralization. The first visible change in tooth enamel is a translucent zone, and represents approximately 1 to 2 mineral loss from the enamel (Fig. 7.5). Tooth cavity formation is still reversible at this stage by calcium (or other minerals) and phosphate diffusing into the subsurface lesion and remineralizing the tooth. If further demineralization occurs to approximately 25 of a lesion in the enamel a visible...

Conclusions And Future Directions

PET provides the opportunity to image multiple dynamic biological processes in situ in brain tumors. Energy metabolism and amino acid transport and incorporation are important components of the pathophysiology of gliomas about which molecular imaging is providing regional biological information that is useful in clinical practice. Imaging hypoxia is straightforward and proliferation imaging with FLT shows significant promise. Neither has been exploited thoroughly enough to allow judgment of their potential benefit to the practice of neuro-oncology. Whereas cell division is the most distinguishing function ofgrowth in tumors, probing membrane biosynthesis with PET and 1- C-11 acetate or a choline tracer may yield information as helpful as protein or DNA synthesis. Because astrocytic gliomas frequently carry epidermal growth factor receptor mutations at a frequency that is related to grade, a PET tracer specific for this mutated receptor could be useful for grading and prognosis (127)....

Other Gsk3 Substrates Relevant To Alzheimers Disease

GSK-3 is a multifunctional kinase that phosphorylates cytoskeletal proteins, metabolic enzymes and transcription factors. Thus GSK-3 deregulation may cause neurodegeneration by several pathways in addition to Tau hyperphos-phorylation. Some of these proteins (i.e., P-catenin, APP, PS-1 and 2) have been already discussed. However, there are other GSK-3 substrates that can be also related to neurodegeneration. Thus pyruvate dehydrogenase when phosphorylated by GSK-3 is known to lead to mitochondrial dysfunction 88 . Inhibition of PDH by GSK-3 may alter energy metabolism and acetylcholine synthesis, an abnormality present in the brain of patients with AD.

Physiologic Effects Of Hyperbaric Oxygen On Wound Healing Processes

Abstract The value of hyperbaric oxygenation has been well established in the treatment of hypoxic and ischemic wounds in which local oxygen tensions are below optimal for healing. The greatest benefit of hyperbaric oxygen therapy is achieved in situations where the nutritive flow and oxygen supply to the repair tissue are compromised by local injury or infection, but in which the regional vascular network, a prerequisite for oxygen to reach tissues is intact or only partly damaged. On the other hand, hyperbaric oxygen seems to possess significant angiogenic potential in tissues suffering from chronic lack of oxygen due to defective vasculature. During wound healing the presence of oxygen takes on additional importance because of the increased demand of reparative processes like cell proliferation and synthesis of collagen. In addition, superoxide generation by polymorphonuclear leukocytes, which is essential for bacterial killing, is critically dependent on tissue oxygen levels....

Zebrafish For A Model Of Nutritionrelated And Agedependent Chronic Diseases With Oxidative Stress

The increasing prevalence of obesity and other nutrition-related chronic diseases, which usually accompany aging, has prompted considerable efforts to understand their pathogenesis and treatment. One experimental approach is to overexpress, inactivate, or manipulate specific genes that regulate energy metabolism and fat storage. Many such techniques are fully amenable and have been established as routine tools in zebrafish, as well as in Drosophila and C. elegans. In the future, these elegant models will be complementarily helpful in dissecting endocrine problems and metabolic pathways, associated with aging and senescence. Particularly, once zebrafish counterparts of essential signaling molecules, such as Sir2 and FoxOs, involved in regulation of energy

Avian Longevity Is Consistent With Evolutionary Predictions

Why do birds live so long In the past, it was often argued that life spans and aging rates in warm-blooded vertebrates were constrained by the ''rate of living'' (Pearl, 1928 Rose, 1991). This argument was based on a robust, positive correlation between animals' body size and longevity, and an equally strong, inverse association between life spans and basal metabolic rates. This generalization is clearly refuted, however, when the long life spans of birds and bats are compared with those of nonflying relatives of similar size. These disproportionately long-lived animals are particularly interesting to comparative gerontologists, especially considering the higher metabolic rates and lifetime oxygen expenditures

Birds May Have Special Cellular And Molecular Adaptations For Delaying Aging

Avian defenses against ROS damage There is growing experimental evidence that birds have unusually effective defenses against aging-related damage to specific tissues, cells, and molecules. Reactive oxygen species (ROS) are now implicated in a growing assortment of aging-related deteriorative processes. Since they are a normal by-product of oxidative metabolism, ROS theoretically should be generated at higher rates by organisms, like birds, with high metabolic rates. But data collected over the past decade using birds from several different orders, including canaries, pigeons, budgerigars and starlings, suggest that birds have better defenses against oxidative damage than short-lived Data from the veterinary clinical literature on a wide taxonomic range of bird species show that healthy birds' blood glucose levels are typically two to three times higher than those of normal mammals. Glucose interacts with proteins, nucleic acids, and other molecules through a series of nonenzymatic...

Concluding Remarks

Furthermore, although not discussed extensively in this review, numerous recent studies have provided a more complete understanding of GSK-3's role in diverse neurological processes strengthening the hypothesis that GSK-3 may represent a therapeutically relevant target of lithium. These include neuropro-tective effects, modulation of circadian rhythms, modulation of monaminergic mediated signaling events, response element binding of neurohormones and P-catenin, and metabolic effects 144 . These distinct pathways have convergent effects on cellular processes such as bioenergetics (energy metabolism), neuro-plasticity, neurogenesis, resilience, and survival (see 144 for a current review). Thus our hypothesis is that lithium (and other medications) may act by enhancing these processes through inhibition of GSK-3.

Micronutrients Alleviating Nutritional Disorders By Nutraceuticals

And in both cases the numbers are rising (4,22-25). Even though micronutrients are needed in minute quantities (i.e., micrograms to milligrams per day), they have tremendous impact on human health and well-being (Tables 5.1, 5.2) (22,26,27). Insufficient dietary intake of these microcomponents impairs the functions of the brain, the immune and reproductive systems, and energy metabolism (26,27).

Bats as a Novel Model for Aging Research

Despite small body size and high metabolic rate, bats are exceptionally long-lived mammals. This longevity, the ecological, behavioral and morphological diversity, and the unique life history traits of this multispecied order of mammals make bats well-suited as model systems for aging research. Including bats in comparative investigations may provide insight into universal mechanisms of senescence as well as reveal mechanisms that confer resistance to expected senescent processes. In this chapter we provide a general description of this extraordinary order of mammals within the context of their potential use for aging research. We describe general methodologies including captive care, capturing and aging techniques as well as some of the health precautions researchers should observe when working with bats. We conclude with a brief summary of the current state of longevity and senescence research on bats and potential future lines of research. Probably most useful is a list of...

Aging Research on Bats

Deterioration (Barclay and Harder, 2003). However, it does not account for the fact that all known bat longevity records exceed those of similar sized nonflying mammals, including those that hibernate (Austad and Fischer, 1991). In its original formulation, the rate of living theory predicts the existence of a constant mass-specific lifetime energy expenditure for all mammals (Sacher, 1959). Bats exceed the lifetime energy expenditure of nonflying placental mammals by two-fold (Austad and Fischer, 1991), contradicting the rate of living theory. Another formulation of the rate of living theory describes an inverse correlation between maximum lifespan and metabolic rate or body size. Austad and Fischer (1991) calculated that on average bats live over three times longer than expected based on body size, again contradicting the rate of living theory. There is ambiguous evidence regarding a possible correlation between body mass and longevity within the order Chiroptera. Two studies found...

Functions of the Adrenal Medulla

The cells of the adrenal medulla secrete epinephrine and nor-epinephrine in an approximate ratio of 4 to 1, respectively. The effects of these catecholamine hormones are similar to those caused by stimulation of the sympathetic nervous system, except that the hormonal effect lasts about ten times longer. The hormones from the adrenal medulla increase the cardiac output and heart rate, dilate coronary blood vessels, increase mental alertness, increase the respiratory rate, and elevate the metabolic rate.

Thyroid and Parathyroid Glands

The thyroid secretes thyroxine (T4) and triiodothyronine (T3), which are needed for proper growth and development and which are primarily responsible for determining the basal metabolic rate (BMR). The parathyroid glands secrete parathyroid hormone, which helps to raise the blood Ca2+ concentration.

Production and Action of Thyroid Hormones

The transport of thyroid hormones through the blood and their mechanism of action at the cellular level was described earlier in this chapter. Through the activation of genes, thyroid hormones stimulate protein synthesis, promote maturation of the nervous system, and increase the rate of cell respiration in most tissues of the body. Through this action, thyroxine (after it is converted into T3) elevates the basal metabolic rate (BMR, discussed in chapter 19), which is the resting rate of calorie expenditure by the body.

The Role Of Mitochondria In Embryo Development

Mitochondria play a key role in the physiology of eukaryotic cells. They are important for mammalian oocyte and preimplantation embryo development, as well as for nuclear transplantation and stem cells (Bavister and Squirrell, 2000 Cummins, 2001a, 2002 Hiendleder and Wolf, 2003). This is not only due to the fundamental role of mitochondria in energy metabolism, but also because they are semi-autonomous organelles and each one contains one or several copies of its genome (mtDNA) that must be replicated during embryo development. In humans, the mitochondrial genome is a 16.6kb circular strand of DNA encoding 37 genes. These include 13 components of the oxidative phosphorylation (OXPHOS) pathway, two ribosomal RNAs and 22 transfer RNAs. The coding capacity of mtDNA is quite limited, because over 200 of the genes needed for mitochondrial function actually reside in the cell's nuclear genome (Cummins, 2001a). This indicates that most of the original mitochondrial genome has migrated to the...

Neurobiology of the Aging Brain

Brain energy metabolism also declines in aging, which involves a decay in the mitochondrial metabolic competence that can be considered an unfavorable condition affecting several other processes such as calcium home-ostasis and the development of SP and NFT. Nonhuman primates and transgenic mice, presently adopted as animal models to investigate human brain aging and AD, may further our understanding of the mechanisms underlying the formation of Alzheimer-like alterations, and may help to set up intervention strategies leading to an increase of the percent of cognitive intact and successfully aged subjects.

Model Body Size And Scaling

It is well known that the metabolic rate of small animals is much higher than that of large animals. It has also been demonstrated that capillary density in animals smaller than rabbits increases dramatically with decreasing body weight.29 However, considering that most animals are similar in having heart weights just above 0.5 of their body weight and a blood volume corresponding to 7 of the body weight, it becomes obvious that to supply the tissues of small animals with sufficient oxygen for their high metabolic rate, it is not sufficient to increase the stroke volume. The stroke volume is limited by the size of the heart, and heart frequency is the only parameter to increase, which results in heart rates well over 500 per minute in the smallest mammals. Other physiological variables, like respiration and food intake, are similarly affected by the high metabolic rate of small mammals. However, metabolism or detoxification and excretion of a drug are not directly correlated with body...

Consumption of soybean and reduced incidence of disease Control of Energy Metabolism and Oxidative Stress in a Healthy Cell Control of Energy Metabolism and Oxidative Stress in a Tumorigenic Cell Many of the diseases for which a reduced risk of incidence has been associated with soy food consumption are oxidation linked diseases, such as cancer and cardiovascular disease (100). Oxidation linked diseases have been linked to a general breakdown in the regulation of cellular activities (such as growth or energy production), an accumulation of ROS such as superoxide and hydrogen peroxide, a cellular redox imbalance, and accumulated oxida-tive damage in normal cells (106). In addition to an abnormal energy metabolism, tumor cells possess a reduced antioxidant response system. Catalase and CuZnSOD activities, important for controlling cytosolic ROS levels, are decreased in numerous cancer cell lines (113,114). Low activity of antioxidant enzymes leaves cancer cells particularly susceptible to increased oxidative damage upon ROS...

Energy Requirements of Skeletal Muscles

Skeletal muscles generate ATP through aerobic and anaerobic respiration and through the use of phosphate groups donated by creatine phosphate.The aerobic and anaerobic abilities of skeletal muscle fibers differ according to muscle fiber type, which are described according to their speed of contraction, color,and major mode of energy metabolism.

Action of the soybean isoflavone genistein

Stimulation of mitochondrial PDH in the tumor cell by phenolic antioxidants such as genistein should cause a demand for proline (117) that would have several major metabolic effects (1) increased mitochondrial oxPHOS supported by proline oxidation would generate increased ROS that could leak into the cytosol and damage essential cellular components (2) proline would be shunted to the mitochondria and away from collagen biosynthesis, potentially crippling tumor growth, expansion, and proliferation activities and (3) energy metabolism would be redirected toward proline mediated mitochondrial ATP synthesis and away from TCA linked, NADH mediated oxPHOS via activity of the PL-PPP. An occurrence of these metabolic effects would be uniquely detrimental to the functioning of a tumor cell because, by all reported indications, normal cellular metabolism, including Finally, and perhaps most importantly, induction of mitochondrial PDH activity and proline cycling by genistein would shift...

Background PI3KAktTSCmTOR Signaling

Activated Akt affects multiple cellular targets that increase metabolism, growth and proliferation while suppressing apoptosis (Summers et al. 1998 Ueki et al. 1998 Cass et al. 1999 Datta et al. 1999 Hill et al. 1999 Plas and Thompson 2005). All of these are beneficial to HCMV lytic growth. Thus, it is not surprising that Akt is activated during HCMV infection (Johnson et al. 2001 Yu and Alwine 2002 Kudchodkar et al. 2006). One of the downstream effects of activated Akt is the activation of mTOR kinase (also known as RAFT1 or FRAP) in mTOR complex 1 (mTORC1, Fig. 1, described in detail in Sect. 3 below). Activation of mTORC1 is critical for the maintenance of cap-dependent translation.

The Link Between Birth Weight and Later Health

While most clinical attention has been focused on premature and SGA babies, there is a complementary literature indicating that excessive fetal growth can present a different set of problems. With large-for-gestational age babies (LGA), there is a significant increase in obstetrical complications and need for caesarian delivery (Gregory et al, 1998). In addition, these infants are more likely to continue on the path toward obesity during childhood and adulthood, especially after diabetic pregnancies (Law et al, 1992). Longitudinal studies show they are predisposed to have poorer glucoregu-lation and to develop type 2 diabetes as adults. Here too, basic science studies in animals have provided considerable support for these associations and revealed several critical mediating pathways linking accentuated growth rates and later disease. For example, pregnant dams fed a high caloric diet will gestate offspring with a distinctive insulin response and altered pancreatic size and renal...

Aging And Longevity Of Species

The best experimental intervention so far, which can extend life span in rodents and in multiple invertebrate species and reliably retard aging and age-related degenerative diseases, is dietary caloric restriction (CR). Gene and protein expression profiles are profoundly altered as a consequence of dietary CR. In particular, several molecular chaperones are induced to protect cells from stress, by preserving not only protein structures but also general cellular structure, increasing the levels of GSH, inhibiting apoptotic death, and maintaining a pool of vital proteins (Li et al., 2004). Life-span studies due to CR in nonhuman primates have not yet been completed, but recent data indicate the beneficial effects of CR on a number of physiological markers. The effects of CR on human metabolism are various, but the specific mechanism(s) that lead to its positive effect on life span are not completely understood, but they might coincide with other well-described...

Biological Correlates of Gender

In addition to having more X chromosomes than males, females generally have a lower metabolic rate, a higher brain-to-body weight, and a lower level of testosterone. Could it be that such differences are responsible for behavioral and cognitive differences between the sexes The possibility that female hormones have a protective effect and that male hormones promote certain disorders has been the subject of continuing research and controversy (Luria et al., 1982 Waldron, 1983). Sex hormones have also been found to be related to cognitive abilities. For example, Hier and Crowley (1982) obtained a positive correlation between spatial ability and secretions of male sex hormones during puberty. In addition, the results of several investigations suggest that testosterone, the most important male hormone, slows the development of the left hemisphere and enhances the development of the right hemisphere of the brain. Note that the right hemisphere is associated with the types of reasoning...

Regulation of Blood Flow Through Skeletal Muscles

As exercise progresses, the vasodilation and increased skeletal muscle blood flow that occur are almost entirely due to intrinsic metabolic control. The high metabolic rate of skeletal muscles during exercise causes local changes, such as increased carbon dioxide concentrations, decreased pH (due to carbonic acid and lactic acid), decreased oxygen, increased extracellular K+, and the secretion of adenosine. As in the intrinsic control of the coronary circulation, these changes cause vasodilation of ar-terioles in skeletal muscles. This decreases the vascular resistance and increases the rate of blood flow. As a result of these changes, skeletal muscles can receive as much as 85 of the total blood flow in the body during maximal exercise.

Unique Electrical Profile of Vascular Smooth Muscle

Second, the resting Em level of -35 to -50 mV in vascular smooth muscle cells is considerably less negative than the Em range of -70 to -90 mV in neuronal or cardiac cells. In effect, the more positive Em level provides for the steady-state activation of voltage-gated Ca2+ channels, which provides a sufficient Caji to mediate Ca2+-dependent vascular tone in small arteries. Third, whereas neurons and cardiac myocytes rely on spontaneously electrical activity for the repetitive secretion of neurotransmitters and cardiac pacemaker activity, respectively, most types of vascular smooth muscle cells do not demonstrate spontaneous electrical activity under normal conditions. Rather, they rely on graded changes in Em to provide activator Ca2+ for tonic contraction. In the systemic circulation, this tonic activation of vascular smooth stabilizes vascular resistance to prevent rapid fluctuations in blood pressure. At the local level, it provides for graded changes in blood flow so...

Heritability of intermediate traits

Controlled, inherited factors influencing either energy expenditure or nutrient partitioning have an important influence on weight gain. Similar data was obtained by the same group when inducing negative energy balance in identical twin pairs (Bouchard et al., 1996). Bouchard and Tremblay have shown that about 40 of the variance in resting metabolic rate, thermic effect of food and energy cost of low to moderate intensity exercise may be explained by inherited characteristics (Bouchard and Tremblay, 1990). In addition, significant familial resemblance for level of habitual physical activity has been reported in a large cohort of healthy female twins (Samaras et al., 1999). While recognizing the great difficulties inherent in the measurement of voluntary food intake, some limited twin data suggest that there are likely to be genetic influences on the overall intake of nutrients, size and frequency of meals and intake of particular foods (Wade et al., 1981).

Methodological issues in the hunt for human obesity genes

Some studies either focus on, or incorporate ''intermediate phenotypes'' in their analyses. Such traits have the theoretical advantage that they may be more proximally related to the function of the gene under study. Thus, a gene which influences energy expenditure might be easier to identify if one studied resting metabolic rate as the outcome variable. Intermediate phenotypes that are frequently used include resting metabolic rate, respiratory quotient (RQ), insulin sensitivity, and food intake and preferences measured using questionnaire-based methods.

Response to leptin therapy

Congenitally leptin-deficient children (Farooqi et al., 1999 2002). The major effect of leptin was on appetite with normalisation of hyperphagia. Leptin therapy reduced energy intake during an 18MJ ad libitum test meal by up to 84 (Farooqi et al., 2002). We were unable to demonstrate a major effect of leptin on basal metabolic rate or free-living energy expenditure, but, as weight loss by other means is associated with a decrease in (BMR) basal metabolic rate, the fact that energy expenditure did not fall in our leptin-deficient subjects is notable. The administration of leptin-permitted progression of appropriately timed pubertal development in the single child of appropriate age and did not cause the early onset of puberty in the younger children (Farooqi et al., 2002). Leptin also reversed the T cell dysfunction and caused a switch from a predominantly TH2 to a TH1 immune phenotype (Farooqi et al., 2002).

The Sympatho AdrenalMedullary System

Affects resting metabolic rate, lipolysis, and thermogenesis SNS overactivity is associated to visceral obesity (Tentolouris et al, 2006). Through actions on ascending vagal afferents, elevated systemic levels of epinephrine may possibly affect cognitive processes, such as memory and attention. An inverted U shape of catecholamine actions has been proposed, with moderate levels being beneficial, while low or high levels impairing cognitive performance (Lundberg, 2000 Roozendaal et al, 2009).

Insulin Receptor Signaling

Insulin and insulin-like growth factor-1 (IGF-1) signaling pathways have been implicated in aging of several experimental organisms (Pardee et al., 2004). This pathway is critical to coordinating the influx of calories with the metabolic rate. Down-regulation of this pathway through caloric restriction is associated with increased life span in mice, worms, flies, and yeast (Barbieri et al., 2003). One of the key transcription factors implicated in aging, namely, FOXO, is regulated by insulin and IGF-1. The FOXO homolog in worms, DAF-16, has a central role in imparting longevity of worms with mutations in the insulin IGF-1 signaling pathway genes, such as daf-2 and age-1 (Kenyon et al., 1993). Over-expression of dFOXO in worms and DAF-16 in flies extends life span through interactions with a host of other nuclear receptors, particularly the PPARs (Giannakou et al., 2004 Henderson and Johnson, 2003). These receptors are up-regulated during caloric restriction, and overexpression of PPAR...

Conceptual Framework The Cycle of Frailty

In the center of this figure, physiologic declines related to aging, including loss of skeletal muscle mass (sarcopenia), declines in resting metabolic rate, energy expenditure, and nutritional status reinforce declines in each system. This in turn influences other physiologic systems, including facilitating declines in insulin sensitivity, V02 max, strength, and power. These changes then contribute to a subcycle of disability, functional decline, and low levels of activity, which in turn reinforces the physiologic decline. Importantly, this model also provides a model for multiple possible entry points into this cycle of decline, and illustrates how specific illnesses, injuries, or medications can trigger and or accelerate this cycle of frailty.

Evolution and systematics

Pleistocene, that the didelphids again entered North America. Throughout this time they retained a remarkably stable morphology. The connection between North and South America also allowed the entrance of other placental mammals into South America. For the first time in 20 million years, marsupials again faced the faster, larger-brained pla-cental competitors and predators. Groups like the Borhyaenids (wolf- or hyena-like marsupials) and Thylacos-milids (marsupial saber-toothed cats) disappeared and gave way to true canids and felids. Some factors that may have contributed to their disappearance are the smaller en-cephalization quotient, lower metabolic rate and overall speed, and lower cursorial abilities of the marsupials compared to their placental counterparts. Didelphids have relatively low evolutionary rates and a strong stabilizing selection that prevents greater morphological diversification in the group.

Across Species Risk Prediction

Quantitatively, although measures of carcinogenic activity in different species are highly correlated, the best means of calibrating the potency in one species for prediction of potency in a second species remains unclear, despite 25 years of discussion and research. The efforts have been limited by the ability to obtain precise estimates of cancer potency for the known human carcinogens. The problem of cross-species prediction is often framed as the selection of the best dose metric. Conceptually, when dose is expressed in the correct metric, exposure to the same dose in different species results in the same risk. The most commonly used metrics are (a) average daily dose, for example, in units milligrams per kilogram bodyweight (mg kgVday) (b) mg per surface area, also called two thirds scaling, or mg kg2 3 day (c) mg kg3 4 day (three-quarters scaling), which corresponds roughly to scaling with metabolic rate and (d) cumulative dose (e.g., total mg kg received throughout life).

PTPs and Human Disease

Recent progress in establishing links between PTPs and human diseases, together with developments in understanding the function of several of these enzymes, has raised awareness of the PTPs in the pharmaceutical industry. The appreciation that PTPs have the ability to display specificity for substrates in vivo and, therefore, to exert effects that would be restricted to specific signaling pathways suggests that PTP-directed drugs would induce defined, rather than global, changes in cellular tyrosine phosphorylation. A spectacular example of the potential importance of PTPs in the development of novel therapeutic strategies was provided by the phenotype of the PTP1B knockout mouse. The mice show no obvious deleterious effects however, they display enhanced sensitivity to insulin and a resistance to obesity induced by a high-fat diet, which is accompanied by increased basal metabolic rate and total energy expenditure 59,80 . These effects have been defined in terms of a regulatory...

And Caloric Requirements

The total rate of body metabolism, or the metabolic rate, can be measured by either the amount of heat generated by the body or by the amount of oxygen consumed by the body per minute. This rate is influenced by a variety of factors. For example, the metabolic rate is increased by physical activity and by eating. The increased rate of metabolism that accompanies the assimilation of food can last more than 6 hours after a meal. Body temperature is also an important factor in determining metabolic rate. The reasons for this are twofold (1) temperature itself influences the rate of chemical reactions and (2) the hypothalamus contains temperature control centers, as well as temperature-sensitive cells that act as sensors for changes in body temperature. In response to deviations from a set point for body temperature (chapter 1), the control areas of the hypothalamus can direct physiological responses that help to correct the deviations and maintain a constant body temperature. Changes in...

Lieve Naesens Leen De Bolle Erik De Clercq

Propagation of HHV-6A or HHV-6B strains, respectively. Other T-lymphoblast lines such as SupT-1 and MT4 are less efficient in supporting HHV-6 replication (De Bolle et al., 2005b). The continuous nature of these T-cell lines ensures that the antiviral data are consistent. On the other hand, the high metabolic rate of these rapidly dividing cell lines increases their sensitivity to the cytotoxic effects exerted by the antiviral test compounds. In addition, these tumor cells may carry mutations that affect basic pathways such as nucleoside metabolism, signal transduction or cell cycle regulation. For antiviral compounds that depend on cellular factors for their activation or antiviral target, these mutations may result in cell-type-dependent antiviral effects. Therefore, primary human lymphocytes isolated from peripheral blood or cord blood provide a more relevant test system to confirm the anti-HHV-6 activity and selectivity of new compounds. Antiviral evaluation in primary or...

Review Activities

The basal metabolic rate is determined primarily by b. The metabolic rate will be increased over basal conditions. Compare the metabolic effects of 3. Describe how thyroxine affects cell respiration. Why does a person who is hypothyroid have a tendency to gain weight and less tolerance for cold Compare and contrast the metabolic effects of thyroxine and growth hormone.

The Origin of the Code

Have heard so often that genes are self-replicating. Actually, many protein enzymes are involved in DNA reproduction (see chapter 17). This has led to a longstanding paradox DNA needs proteins in order to function, and yet proteins cannot be made without DNA. Sidney Altman of Yale University and Thomas Cech of the University of Colorado provided one possible solution. They were awarded a Nobel Prize in 1989 for showing that RNAs can function as enzymes, called ribozymes. The first replicator may not have been DNA, but rather RNA, which could act as both template and agent of its own reproduction. Molecular biologists have envisioned an RNA world of self-reproducing entities, the forerunners of the gene. Certainly one could envisage alternatives. Some theorists have suggested the existence of self-reproducing polypeptides, others have argued that a membrane-bound metabolic system would have emerged first, and perhaps replicating molecules developed within it.22 Still others suggest...

Rate Of Living Metabolism And Oxidative Damage

Thus, increased lifespan in flies at lower temperatures was originally thought to be due to slowing down of all biochemical processes. However, the interpretation of effects of temperature may not be so simple because not all enzyme activities are affected by temperature to the same degree. Concentration of a molecule X depends on its production and consumption, and if the activities of the producer and the consumer have different Q10 values (thus differently affected by temperature) the concentration of molecule X could go up or down, depending on the balance. Furthermore, there are certain physiological responses to cold (temperature compensation) that are independent of metabolic rate, such as changes in membrane fatty acid composition, that can affect susceptibility to oxidative damage (unpublished observation). It is not known how circadian rhythms, which are known to control various physiological functions, are affected by temperature, although a constant 12 12 hour light dark...

Dietary prevention of chronic heart failure CHF the role of micronutrients dietary fatty acids and reduced sodium intake

Finally, it has been shown that up to 50 per cent of patients suffering from CHF are malnourished to some degree,61 and CHF is often associated with weight loss. There may be multiple aetiologies to the weight loss,62 in particular lack of activity resulting in loss of muscle bulk and increased resting metabolic rate. There is also a shift towards catabolism with insulin resistance and increased catabolic relative to anabolic steroids.63 TNF, sometimes called cachectin (see above), is higher in many patients with CHF,53,63 which may explain weight loss in these patients. Interestingly, there is a positive correlation between TNF and markers of oxidative stress in the failing heart64 suggesting a link between TNF and antioxidant defences in CHF (the potential importance of TNF in CHF is discussed below in the section on dietary fatty acids and CHF). Finally, cardiac cachexia is a well-recognised complication of CHF, its prevalence increases as symptoms worsen65 and it is an independent...

Behavior And Reproduction

Todies are homeotherms that is, they have body temperatures like humans in which metabolic rates and temperatures are controlled. At times, todies can become very inactive to conserve energy. Such dormant periods occur when they cannot eat because of the darkness at night and during long periods of heavy rain. Females also become dormant in order to save their energy while breeding. Todies do not migrate.

Seven Day Physical Activity Recall

Sallis et al, 1985), a semi-structured interview designed to evaluate self-reported activity levels over a 7-day period. A self-report version of this questionnaire is also available. Respondents are asked to estimate the total time spent in sleep or engaged in occupational, household, or leisure activities of at least moderate intensity. Examples of moderate (e.g., brisk walking), hard (e.g., physical labor), and very hard (e.g., jogging) activities are provided. The energy expenditure for each activity is expressed in multiples of resting metabolic rate (MET 1 MET 1 kcal kg h). The MET for each activity is multiplied by hours spent in the activity, and the products are summed to provide an estimate of total energy expenditure.

Ocular Use Of Steroids

Glucocorticoids have important dose-related effects on carbohydrate, protein, and fat metabolism. Glucocorticoids increase serum glucose levels and thus stimulate insulin release and inhibit the uptake of glucose by muscle cells, while they stimulate hormone-sensitive lipase and thus lipolysis. The increased insulin secretion stimulates lipogenesis and, to a lesser degree, inhibits lipolysis, leading to a net increase in fat deposition combined with increased release of fatty acids and glycerol into the circulation. Glucocorticoids promote fat redistribution in the body.

Effect of hyperoxia on VO2 of the healthy subject at exercise


Controversial observations and interpretations have been made about the quantity of oxygen uptake in the exercising subject some authors have found an increase of VO2 max with increased DO2 in human24 and animal25 studies, which has not been observed by others26'27. Nevertheless, most authors have observed a better exercise endurance and a decrease of serum lactate levels, suggesting additional hyperoxia-induced metabolic effects.

Cranberry synergies with functional phytochemicals and other fruit extracts

Recent research has documented the evidence that whole foods, and not single compounds, have a better functionality in maintaining our health against many of the antioxidant diseases. Recent work on the effect of wine has shown that resveratrol is responsible for the decrease in atherogenesis in rats (101,102). However, when resveratrol was used as a supplement in diet such an effect was not seen. Other researchers have shown that the combination of resve-ratrol and quercetin exerts a synergic effect in the inhibition of growth and proliferation of human oral squamous carcinoma cells (221). Carbonneau et al. (223) during in vivo antioxi-dant assays with red wine, observed that different phenolics in wine could play a coantioxi-dant role, similar to that described for vitamin C, and a sparing role toward vitamin E, which increases due to supplementation with phenolics. Synergistic interactions between wine polyphenols, quercetin, and resveratrol were found to decrease the inducible...

The hostmicrobe interface within the gut

Fig. 5.1 Functions of the intestinal microbiota. Commensal bacteria exert a miscellany of protective, structural and metabolic effects on the intestinal epithelium. Fig. 5.1 Functions of the intestinal microbiota. Commensal bacteria exert a miscellany of protective, structural and metabolic effects on the intestinal epithelium.

Gut Bacterial Metabolism and CRC Risk

A major role for the intestinal microbiota has been identified in the metabolism of the bile acids. The primary bile acids, chenodeoxycholic acid and cholic acid, are subject to extensive metabolism by the intestinal microbiota (53), predominantly 7-a-dehydroxylation, which converts cholic to deoxycholic acid (DCA) and chenodeoxycholic acid to lithocholic acid (LCA). These secondary bile acids exert a range of biological and metabolic effects in vitro and in vivo including cell necrosis, hyperplasia, and tumor-promoting activity in the colon, induction of DNA damage and apoptosis (54). It has also been suggested that secondary bile acids influence CRC by selecting for apoptosis-resistant cells or by interacting with various secondary messenger signaling systems.

Regulatory Functions of Adipose Tissue

It is difficult for a person to lose (or gain) weight, many scientists believe, because the body has negative feedback loops that act to defend a particular body weight, or more accurately, the amount of adipose tissue. This regulatory system has been called an adipostat. When a person eats more than is needed to maintain the set point of adipose tissue, the person's metabolic rate increases and hunger decreases, as previously described. Homeostasis of body weight implies negative feedback loops. Hunger and metabolism (acting through food and hormones) affect adi

Biomarkers of Healthy Eating

Biomarkers may be measured in a wide range of tissues that include plasma, serum, red blood cells, white blood cells, feces, urine, hair, nail, buccal cells, and a number of measures specifically designed to assess overall antioxidant capacity (Polidori et al., 2001), metabolic state (e.g., exhaled air), or the extent of DNA damage (Potischman, 2003a, 2003b). Some tissues seem especially relevant to aging studies (e.g., lipid content of red blood cell membranes Hulbert et al., 2004), but it is best to plan to collect diverse types of samples before drawing any general conclusions. This is true in most biomarker studies whenever possible, ensure that the chosen marker is examined or tested in at least two biological systems (Ilich et al., 2003). Before deciding upon any biomarker, it is always useful to discuss the choice with the laboratory where the tests will be conducted. This advice often includes appraisal of recent analytical developments, the competing interests of high...

Bats as Models for Aging Research Advantages and Disadvantages

Heterothermic bats are metabolically malleable. A researcher can increase or decrease the metabolic rate of a bat by exposing it to lower or higher temperatures and, with the appropriate environmental cues, a bat may even enter torpor or hibernation. This plasticity makes bats an ideal system to study the role of metabolism and metabolic pathways in determining longevity and rates of senescence. Researchers will find extensive information in the literature on the physiology and metabolism of bats, though it should be noted that studies have focused on only a few bat families and not all species within a family can enter torpor. On the other hand, this prompt flexibility may pose a problem for studies where metabolic state should remain constant, especially caloric restriction studies, as bats may enter torpor in response to food scarcity (Brunet-Rossinni and Austad, 2004).

Lipid Signaling

The elucidation of cell signaling mechanisms and the variety of molecules that are employed in these myriad of processes is particularly well exemplified by the lipid messengers. Except for the above mentioned steroid hormones, lipids have long been thought to function mainly in energy metabolism and membrane structure. This last decade has culminated in the broad recognition that membrane phos-pholipids provide many of the important cell signaling molecules via phospholipases and lipid kinases. Key is the role of phospholipase C in hydrolyzing phosphatidylinositol bisphosphate (PIP2) to release diglyceride that activates protein kinase C (PKC) and inositol triphosphate (IP3), which mobilizes intracellular Ca2+, central to so many regulatory processes (see Section II X-Berridge). The phosphorylation of PIP2 at the 3-position to produce PIP3 promotes vesicular trafficking and other cellular processes. Phospholipase D releases phosphatidic acid, and phospholipase A2 provides arachidonic...


Baker's brewer's yeast, Saccharomyces cerevisiae, is a molecular genetic model organism. It is a eukaryote with a nucleus and membrane-bound organelles like mitochondria, peroxisomes, endoplasmic reticulum, and a Golgi complex. As such, complex processes like chromosome replication, transcription and translation, cell division, secretion, membrane trafficking, subcellular compartment structure and function, energy metabolism, cytoskeletal structure and mechanics, and intracellular signaling that are carried out by all eukaryotes can be explored in detail in an organism with a well-developed and simple-to-use genetic system. Saccharomyces is easy to culture and obtain in quantity, thus making it amenable to biochemical analysis. Gene manipulation techniques for Saccharomyces are extremely powerful. The major disadvantage of working with Saccharomyces is cell size, which makes cytological analysis difficult. Nevertheless, continued development of new microscopic techniques and...

Cardiac Maturation

Myocardium has less muscle mass and less cellular organization than the mature myocardium. The newborn myocardium consists of 30 contractile proteins and 70 noncontractile mass (membranes, connective tissues, and organelles), in contrast to the adult myocardium, which is 60 contractile mass (30). The myocardial cells of the fetus are rounded, and both the myocardial cells and myofibrils within them are oriented randomly. As the fetal heart matures, these myofibrils increase in size and number and orient to the long axis of the cell, which further contributes to improved myocardial function (28). The fetal myocardial cell contains higher amounts of glycogen than the mature myocardium, suggesting a higher dependence on glucose for energy production in experiments in nonprimate model systems, the fetal myocardium is able to meet its metabolic needs with lactate and glucose as the only fuels (33). In contrast, the preferred substrate for energy metabolism in the adult heart is long-chain...

Future trends

Taking into account the safety aspects, i.e. the possibility of infection increase, adverse metabolic effects, excessive stimulation of immunological systems and potential gene transfer, the manufacturer of probiotics is obliged to present clinical documentation showing the absence of the above effects.17 In particular, probiotic bacteria must not significantly increase the risk of transfer of antibiotic resistance and cannot possess haemolytic activity.


Most aquatic animals are ectotherms, or poikilotherms, or what is often referred to as cold-blooded. As the temperature of the surrounding water rises and falls, so does their body temperature and, consequently, their metabolic rate. Many become quite sluggish in unusually cold water. This slowing down caused by cold water is a disadvantage for active swimmers. Some large fish, such as certain tunas and sharks, can maintain body temperatures that are considerably

The Brain

The brain has been compared to a digital computer because the neuron, like a switch or valve, either does or does not complete a circuit. But at that point the similarity ends. The switch in the digital computer is constant in its effect, and its effect is large in proportion to the total output of the machine. The effect produced by the neuron varies with its recovery from the refractory phase and with its metabolic state. The number of neurons involved in any action runs into millions so that the influence of any one is negligible Any cell in the system can be dispensed with The brain is an analogical machine, not digital. Analysis of the in-tegrative activities will probably have to be in statistical terms. (Lashley, quoted in Beach, Hebb, Morgan & Nissen, 1960, p. 539)


Lac is generally present in only minute amounts (< 0.5 mM) in the brain and undetectable in normal spectra (114). The lactate peak can be visualized in any condition that results in anaerobic glycolysis such as energy metabolism disorders, hypoxia, stroke, neoplasms, or siezures. It can also be present in macrophages and therefore may be seen with acute inflammation. Lastly, lactate will also accumulate if there is poor washout from the tissue as with cysts, necrotic foci, or infarcts. When present, it is recognized as a doublet with 0.2 ppm peak splitting, centered at 1.32 ppm, and inverted below the baseline at long TEs (e.g., 135 ms) but projected above the baseline at short (e.g., 20 ms) and very long (e.g., 272 ms) TEs.


Another mammalian adaptation is known as non-shivering thermogenesis (NST), the burning of so-called brown fat, a special tissue rich in mitochondria and often deposited around the neck or between the shoulder blades. The most effective way of dealing with the challenge of a cold environment is torpor, the reduction of one's body temperature and basal metabolic rate, in some species to around or even slightly below 32 F (0 C). For example, the Arctic ground squirrel (Sper-mophilus parryii) goes down to a startling body temperature of 28 F (-2 C). Daily torpor, or larger periods of hibernation, can be found in members of at least five placental and two marsupial orders. The largest species found with real torpor, lowering their body temperatures by at least 50 F (10 C), are badgers (both the American and the Eurasian species in the latter case it was found in an individual of 27 lb 13 kg body weight). Bears also become dormant in winter, but their body temperature is lowered only by...

Wound Environment

Conventional thought dictates that lactate must accumulate because of hypoxia, but in wounds this is only partially the case. In wounds the major portion of lactate load is contributed by leukocytes, which derive the great majority of their energy from glycolysis even in the presence of oxygen with the end product of their energy metabolism being lactate. Lactate accumulation is therefore relatively insensitive to changes in oxygen tension in wounds. Lactate, in common with oxygen, excites many cells to release growth factors and cytokines such as TGF-a, VEGF, and IL-1 and 8, and can excite their production in the presence of oxygen. Furthermore, lactate alone can stimulate and govern collagen synthesis and angiogenesis, two of the major components of wound healing.10,11 Hypoxia does not share this property and in fact has the opposite effect.1,6

Genetical Genomics

GWA studies on global gene expression including 400,000 SNPs and 55,000 transcripts representing 20,000 genes was published a few years ago (Dixon et al, 2007). Combinations of genome-wide with transcriptomic or proteomic data or the metabolic response to drugs will provide further insight into the role of genes in complex diseases.

Age Pigments

Lipofuscin accumulates in neurons throughout the CNS and is particularly abundant in cranial and spinal motor nuclei, in large neurons of the precentral gyrus, and in cortical pyramidal cells. Within neurons the lipofuscin mass is reported to displace the nucleolus however, it is not yet proven whether this is due to the excessive accumulation of the pigment or whether the cell first undergoes impairment of function and lipofuscin granules are formed as a consequence of cell deterioration. Although the significance of lipofuscin accumulation in neuronal function is not clear, as a reasonable interpretation, it may be hypothesized that the lipofuscin masses within the neuron may be able to decrease the plastic capacity of the nerve cells to adapt to environmental stimulation. Lipofuscin accumulation has been proposed to be a function of cellular metabolic activity rather than of chronological age and, in this context, repetitive metabolic accidents may lead to the accumulation of a...

Adrenal Androgens

Tion of exogenous leptin to human subjects has no significant effect on weight change, energy intake, or energy expenditure.86 Thus, the relationship of leptin to energy metabolism appears to be different in rodents and humans.87 The effects of energy balance and energy flux on leptin levels may reflect the control of leptin production by factors regulating energy metabolism.94,95 The control of leptin production by insulin has been particularly well demonstrated by recent studies. Leptin levels are more strongly correlated with insulin levels than with adiposity.96,97 Children with new-onset type I (insulin-deficiency) diabetes have abnormally low leptin levels for their fat mass, but those levels quickly rise to the normal range with insulin therapy.98 Similarly, biliopancreatic diversion in obese subjects produces a reduction in both insulin and leptin levels and a dissociation between leptin and fat mass.99 The regulation of leptin production by insulin may underlie the...

Diabetes Mellitus

Debate exists regarding the heights of children and adolescents with newly diagnosed Type 1 diabetes mellitus (IDDM) (32-34), however, it appears that growth deceleration may be seen prior to islet cell failure and overt symptoms of diabetes (35). Further, poor metabolic control of IDDM is associated with chronic elevation of serum GH concentration, growth retardation, and delayed sexual development (36,37). The metabolic effects of the elevated GH concentrations have been implicated as a causative factor in the development of diabetic retinopathy and other microvascular complications (38).


Lower incidences of urinary tract infection and now has been shown to have a capacity to decrease peptic ulcer caused by Helicobacter pylori. Isolated compounds from cranberry have been shown to reduce the risk of CVD and cancer. Functional phenolic antioxidants from cranberry such as ellagic acid have been well documented to have antimutagenic and anticarcinogenic functionality. Even though many benefits have been associated with phytochemicals from cranberry, such as ellagic acid, their mechanism of action is still not very well understood. Emerging research exploring the mechanism of action of these phyto-chemicals from cranberry usually follows a reductionist approach, and is often focused on the disease or pathological target. These approaches to understanding the mechanism of action of phytochemicals have limitations as they are unable to explain the overall preventive mode of action of phenolic phytochemicals. The current proposed mechanisms of action of these phenolic...

Basal Rate

The residual or unstimulated activity of (a) an enzyme reaction, (b) a series of reactions, or (c) the energy metabolism of an individual organism. Although one most frequently considers basal reaction rates in enzyme ki BASAL METABOLIC RATE (or B.M.R.). An index of metabolic activity of an individual organism, usually measured by the rate of oxygen consumption while in a resting, nonsleeping state. The basal metabolic rate can also be determined as the rate of heat evolution in a state of resting and without recent consumption of foodstuffs. Because temperature control is of vital importance to mammals, the basal metabolic rate is roughly proportional to body surface area. A young healthy adult male (mass 70 kg) typically has a basal metabolic rate of 300-350 kJ hour, corresponding to about 70-80 watts.


Carbohydrates22'23 are the body's main energy source 50-55 per cent of the daily caloric intake should be provided by them. It is important that people with either type 1 or type 2 diabetes consume the right amount of carbohydrates, as they are the primary energy source for the central nervous system which depends on blood glucose. Carbohydrates also have the role of 'protein sparer', preventing the use of proteins for energy purposes, allowing them to perform their real role in tissue building and as metabolic primers for fat metabolism. The amount of carbohydrates in the diet regulates the levels of the intermediate products of fat metabolism, ketones. If the amount of carbohydrates is too low or unavailable, fat is oxidized for energy purposes with an increase of ketones


The most common biominerals include calcium phosphate, calcium carbonate, and calcium oxalate. While these substances readily form regular crystals and paracrystals, living systems rely on biospecific binding interactions to achieve exquisite morphological control over the biomineralization process. The complex and varied crystal habits adopted by marine organisms demonstrate how stereospecific intervention can lead to an astonishing variety of shell forms through the directed deposition of the principal ingredient, calcium carbonate. In higher organisms, the diverse morphologies of endoskeleton, exoskeleton, and teeth are achieved (a) by modulating interactions with cell membranes, proteins, and other inorganic and organic electrolytes, and (b) by controlling concentration supersaturation of mineral salts through the action of chelating agents, ion pumps, and energy metabolism. Biominerali-zation also represents an efficient method for removing excess cations,...


Thyroid hormone plays a critical role in regulating metabolism. In hypothyroidism, the basal metabolic rate is decreased due to a lack of thyroid hormone, resulting in bradycardia, cold intolerance, alopecia, and weight gain. Neurologic symptoms are relatively common in hypothyroidism and include paresthesias in up to 80 of patients as well as ataxia, coma, headache, seizure, cerebellar signs, and psychosis (132,133). Cranial nerve involvement has also been reported, with the vestibulocochlear nerve most commonly affected in 15 to 31 of patients with hypothyroidism (132). Involvement of the facial nerve is considered rare. Its mechanism is thought to be a compressive phenomenon. In hypothyroidism, myxedematous infiltration and swelling of the soft tissue are hypothesized to have a compressive effect on the facial nerve through the tight confines of the fallopian canal. Anecdotal reports of facial nerve decompression in hypothyroidism have been described (134), but additional reports...


Infants and young children have relatively higher metabolic rate and energy requirements than adults. In addition to maintenance needs, the child requires nutrition for growth. Enteral feeding is the preferred method of providing fluid, calories (carbohydrate, protein and fat), minerals and vitamins but may not be possible in critically ill or postoperative patients having paralytic ileus. Refinements in parenteral nutrition have undoubtedly been a major factor in the improved outcome of major surgery for infants and children. As a rule, parenteral nutrition should be considered in neonates when there is a delay of > 4 days before adequate enteral feeding can be established. Long-term parenteral nutrition in infants carries the same risks as in adults (metabolic complications, sepsis, venous access problems, etc.) but infants appear to be particularly prone to develop cholestasis which can lead to liver failure.


Harrison RV, Harel N, Hamrahi H, Panesar J, Mori N, Mount RJ (2000) Local haemodynamic changes associated with neural activity in auditory cortex. Acta Oto-laryngol. 120, 255-258 Haxby JV, Horwitz B, Ungerleider LG, Maisog JM, Pietrini P, Grady CL (1994) The functional organization of human extrastriate cortex A PET-rCBF study of selective attention to faces and locations. J. Neurosci. 14, 6336-6353 Haxby JV, Ungerleider LG, Horwitz B, Rapoport SI, Grady CL (1995) Hemispheric differences in neural systems for face working memory A PET-rCBF Study. Human Brain Mapp. 3, 68-82 Horwitz B (1990) Simulating functional interactions in the brain A model for examining correlations between regional cerebral metabolic rates. Int. J. Biomed. Comput. 26, 149-170 Horwitz B (1994) Data analysis paradigms for metabolic-flow data Combining neural modeling and functional neuroimaging. Human Brain Mapp. 2, 112-122 Horwitz B (2003) The elusive concept of brain connectivity. Neuroimage 19, 466-470 Horwitz...

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