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Peripheral Energy Metabolism 6321 p3Adrenergic Receptor

Many of the peptide hormones described exert significant effects on energy metabolism via modulation of nutrient utilization or partitioning of fuel stores, and through effects on the hypothalamic feeding and energy circuits. Peripheral regulation of energy metabolism also occurs the most significant example is the effect of sympathetic activation on p-adrenergic receptors. A number of well-characterized adrenergic receptor subtypes exist, and the signal transduction pathways activated following receptor activation have been well studied. To demonstrate the requirement for p-adrenergic receptors in diet-induced thermogenesis, mice lacking the p3-adrenergic receptor were generated and shown to have modestly increased fat stores.164 Mice lacking p-adrenergic receptors 1, 2, and 3 were also produced.165 They were mildly obese, showed lowered metabolic rates, and were cold intolerant. On a high-fat diet, they became massively obese compared with wild-type controls.

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...

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,...

Metabolic Rate

In 1920, Kurt Noack of Germany compared the metabolic rates of thermophilic and mesophilic fungi at different temperatures. Using the volume of carbon dioxide evolved over time as a measure of the metabolic rate, he compared Thermoascus aurantiacus (a thermophilic fungus) with Penicillium glaucum (a mesophilic fungus), both grown in identical media. The quantity of carbon dioxide released by the mesophilic fungus in 24 hours was equivalent to 67 of its dry weight at 15 C and 133 at 25 C. Noack reasoned that if this fungus could grow at 45 C, the extrapolated value of carbon dioxide according to the van't Hoff rule would be 532 . However, the actual value for the thermophilic fungus used at 45 C was 310 . From this, Noack inferred that at a given temperature the metabolism of a thermophilic fungus is actually slower than what is expected based on the van't Hoff rule.

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...

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. Although...

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...

Class Iii Hdacs In Skeletal Muscle

In mammals, seven homologs of the Saccharomyces cerevisiae HDAC silent information regulator (Sir)2 have been identified and are referred to as class III HDACs (46). Sir2 HDACs uniquely require NAD for activity. In yeast, Sir2 governs life span extension in response to caloric restriction. In vitro studies have revealed a role for mammalian Sir2a in the control of skeletal muscle differentiation. Sir2a is recruited to muscle gene regulatory elements through association with MyoD, resulting in histone hypoacetylation and transcription repression (47). The repressive actions of Sir2a appear to be overcome by changes in metabolic state that normally accompany muscle differentiation. Specifically, in cells undergoing differentiation, the levels of NAD are reduced such that Sir2a catalytic activity is diminished. Sir2a is also abundantly expressed in the heart (48). Thus it will be of interest to determine whether this metabolic sensor controls transcriptional responses to stress in the...

Epinephrine Adrenalin

Ped 0.01 mg kg SC q15 minutes for 2 doses then q4 hrs as needed. Clearance MAO COMT metabolism. Adverse effects may cause hypertension, dysrhythmias, headache, nervousness, nausea vomiting, myocardial ischemia dysrhythmias potentiated by halothane metabolic effects increases adipose tissue lipolysis, liver glycogenolysis, inhibits release of insulin.

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.

Huntingtons disease Huntingtons chorea

Generalized atrophy of the brain is most severe in the frontal lobes, caudate nuclei, and putamen. Low-energy metabolism in the caudate nucleus, identified by PET scan, is characteristic and could be used as a presymptomatic test. Deficiency of GABA and excess dopamine have been demonstrated at post-mortem.

Definition Of Obesity And Bmi Cutoff Points

A second point is that if some ethnic groups have higher body fat percent at a given BMI, their fat-free mass will be lower, resulting in lower metabolic rates for a given weight and height (age and sex). This may shed new light on some reported low values of resting metabolic rate and total daily energy expenditure in certain population groups (53).

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).

Intake Versus Expenditure

It is also likely that the age-related increase in obesity is in some way related to deficits in energy expenditure. This topic has been carefully reviewed (72), and the relationship between resting metabolic rate (RMR) and age appears to be curvilinear if sufficient numbers of older individuals are included. While three-fourths of this decline in RMR can be accounted for by decrements in FFM, one-fourth remains unexplained. Poehlman has suggested that this decline in RMR may be related to inactivity and has demonstrated normalization in older men after endurance training (73). Others have not been able to demonstrate an endurance training-related improvement in RMR in older subjects (74). While the thermic effect of feeding (TEF) may decline with age (75), this may be more related to inactivity than to age itself (72). Furthermore, variability in TEF does not predict subsequent weight gain (76).

Reproductive biology

When eggs are laid, female pythons tightly wrap coils around the eggs and remain with their clutches until they hatch. During incubation, the females of many species of pythons are capable of elevating their body temperatures. A female accomplishes this thermal feat by increasing her metabolic rate either through rhythmic muscle contractions that give the impression that she is shivering or by isotonic muscle contractions that allow her to remain motionless. Some pythons are observed to supplement their thermal exertions during incubation by briefly leaving their clutches to bask and then returning to the task of incubating the eggs when their bodies have been warmed by the sun.

Feeding and digestion

Rattlesnake Illustration Feeding

With species and is generally much less than is required by mammals. Because of low metabolic rates and generally high efficiencies of converting food to assimilated energy, most reptiles do not need food frequently. Results of studies mainly of snakes indicate that physiological responses of the gut are regulated adaptively in relation to foraging modes and feeding habits. After feeding, snakes that feed infrequently on relatively large prey undergo remarkable increases in metabolic rate, mass of intestinal tissue, and rate of nutrient transport across the gut wall. After digestion and between feedings, the gut atrophies, and digestive functions are down-regulated. These changes are more modest in actively foraging snakes that feed with relatively greater frequency and thus maintain the gut in a more constant state of readiness. The down-regulation responses in snakes that feed less frequently presumably evolved to conserve energy otherwise spent on gut maintenance during extended...

A zoologist answers A highly derived amniote

Black Handed Spider Monkey

Many of the characters common to mammals do not appear in other animals. Some of them, of course, can be observed also in birds a very high (in respect to both maximum and mean values) metabolic rate and activity level or complexity of particular adaptations such as advanced parental care and social life, increased sensory capacities, and new pathways of processing sensory information or enormous ecological versatility. Fine differences between birds and mammals suggest that the respective adaptations are homoplasies that is, they evolved in both groups independently.

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...

Physical characteristics

Anatomy Turtlesand Other Creatures

Some interesting metabolic, respiratory, and cardiovascular adaptations are related to aquatic habits. The metabolic rate is relatively low compared with that of other snake species, and the low rate of energy use appears related to the generally sluggish lifestyle of file snakes. Laboratory studies of the Arafura file snake indicate that the capacity for generating metabolic energy is low and cannot sustain vigorous activity for more than a few minutes. These snakes are lung breathers but can remain submerged for several hours. The skin functions as an accessory respiratory organ and exchanges a considerable fraction of oxygen and carbon dioxide when snakes are in well-oxygenated water. Relatively long submergence times are related to the low metabolic rate, cutaneous gas exchange, sluggish behavior, and large oxygen store attributed to the elongated lung and to the presence of a large volume of circulating blood, which contains large amounts of red blood cells and hemoglobin.

In Heart Faliure What Is Gdmp

Exercice Program Heart Failure

Metabolic Effects In general, the metabolic effects mediated via the P-AR system include (1) increases in glycogen formation (via increased glycogenolysis as well as decreased formation of glycogen) (2) the stimulation of lipolysis or (3) increases in ATP production (via glycolysis citrate cycle). Some of these metabolic effects may be mediated via the P3-AR (e.g., control of lipolysis). The P3-AR is also considered to have some regulatory function in cardiac (and vascular) contractility (e.g., negative inotropic effects) (8).

Critical Thinking Questions

A student is accustomed to running three miles each afternoon at a slow, leisurely pace. One day, she runs a mile as fast as she can. Afterwards she is winded, with pains in her chest and leg muscles. She thought she was in great shape What has she experienced, in terms of energy metabolism

Sex Chromosomes and Their Genes

Sperm Blood Vessels

Code a variety of proteins that function in both sexes, participating in or controlling such activities as bone growth, signal transduction, the synthesis of hormones and receptors, and energy metabolism. The members of the second functional group of Y chromosome genes are very similar in DNA sequence to certain genes on the X chromosome, but they are not identical. These genes are expressed in nearly all tissues, including those found only in males. The third group of genes includes those unique to the Y chromosome. Many of them control male fertility, such as the SRY gene. Some cases of male infertility can be traced to tiny deletions of these parts of the Y chromosome. Other genes in this group encode proteins that participate in cell cycle control proteins that regulate gene expression enzymes and protein receptors for immune system biochemicals.

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.

Cardiovascular Effects

Hawthorn flavonoids have also been shown to decrease the cytotoxicity of hypoxia to human umbilical vein endothelial cells in vitro (Lan et al 2005), as well as protect against delayed cell death caused by ischaemia reperfusion brain injury in gerbils (Zhang et al 2004). These effects have been attributed to improving energy metabolism, scavenging oxygen free radicals and inhibiting production of free radicals in ischaemic myocardium (Min et al 2005, Zhang et al 2004).

Exercise and Metabolism

The 24-h energy expenditure can be broken down into several components, including resting metabolic rate (RMR), the thermic effect of feeding, and the energy cost of physical activity. Less than 20 of the RMR is attributed to skeletal muscle (1). Nonetheless, the factor that can cause the most dramatic effect on metabolic rate is strenuous exercise. During strenuous exercise, the total energy expenditure of the body may increase 15-25 times above resting levels (1). This enormous elevation in the body's metabolic rate is the result of a 200-fold increase in the energy requirement of exercising muscles (1). In terms of measurement, the resting energy expenditure of a 70-kg human is approximately 1.2 kcal min (5.0 kJ), whereas the energy cost during strenuous exercise can be 18-30 kcal min (75-125 kJ) (1). At first glance, these numbers look promising for weight loss in that the energy cost of a 60-min exercise bout would be from 1080 to 1800 kcal (4518-7531 kJ). This translates 2...

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...

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...

Major imaging techniques in mental health

Positron emission tomography uses a form of sugar that contains a radioactive atom which emits particles called positrons. The positrons are absorbed to a different extent by cells varying in their metabolic rate. PET scans are especially useful for brain imaging studies and are used to illustrate the differences between brains of people without mental disorders and brains of people with mental disorders. For example, because PET scans can detect brain activity, PET scans of the brains of depressed and non-depressed persons can show

Conceptualization Of The Problem Of Weight Regain

A complex interaction of physiological, environmental, and psychological factors makes the maintenance of lost weight difficult to achieve. Following a period of restrictive dieting, people often experience a heightened sensitivity to palatable food (22). Consequently, exposure to an environment rich in tasty high-fat, high-calorie foods virtually guarantees occasional lapses in dietary control (23,24). Moreover, increased caloric intake during the postdieting period may easily translate into weight regain. During the postdieting period, a variety of physiological processes, including reduced metabolic rate (25-28), changes in catecholamine excretion and thyroid function (29), and increased lipoprotein lipase activity (30,31), may facilitate the regaining of lost weight. Thus, even minor periods of positive energy balance may readily result in weight gain.

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).

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.

The Basic Characteristics Of A Cell

All cells use the DNA-RNA coding system for replication and for coding proteins. All cells are bounded by lipid membranes, although the composition of the membrane varies across cell types. All cells use ATP (adenine 5'-triphosphate) as their source of energy for carrying out metabolic processes. They do this by glycol-ysis, the anaerobic (in the absence of oxygen) breakdown of glucose into lactic acid with a net gain of ATP molecules, or by photosynthesis, the conversion of sunlight into energy either nonoxidatively or oxidatively with a net gain of many more ATP molecules than glycolysis yields. Actually, as we currently understand early life, the evolution of these processes both depended on and drastically altered the Earth's atmosphere, and knowledge about how particular cells make ATP and carry out metabolic processes such as movement, synthesis of various cellular constituents, and the like tells us something about the evolution of life itself. Because much of cellular...

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...

Biomedical Importance

An adult human weighing 70 kg requires about 10-12 MJ (2400-2900 kcal) from metabolic fuels each day. This requirement is met from carbohydrates (40-60 ), lipids (mainly triacylglycerol, 30-40 ), protein (1015 ), and alcohol if consumed. The mix being oxidized varies depending on whether the subject is in the fed or starving state and on the intensity of physical work. The requirement for metabolic fuels is relatively constant throughout the day, since average physical activity only increases metabolic rate by about 40-50 over the basal metabolic rate. However, most people consume their daily intake of metabolic fuels in two or three meals, so there is a need to form reserves of carbohydrate (glycogen in liver and muscle) and lipid (tri-acylglycerol in adipose tissue) for use between meals.

Clinical Presentation

Disease affecting the parathyroid glands usually presents as a consequence of altered function. Hyperparathyroidism describes an altered metabolic state due to increased secretion of parathyroid hormone (parathormone). Rarely seen nowadays is the full spectrum of bones, stones, groans and moans biochemical investigation of non-specific complaints such as profound tiredness, nausea or thirst is the usual method of diagnosis although a small proportion of cases are detected during investigation of patients with organ-specific complaints. Primary hyperparathyroidism is due to an increased secretion of parathormone from one or more of the parathyroid glands, usually caused by an adenoma. Secondary hyperparathyroidism is due to the physiological response of the four parathyroid glands to persistent hypocalcaemia, usually renal failure, malabsorption syndromes or Vitamin D deficiency. Tertiary hyperparathyroidism is a result of persistent autonomous hypersecretion of parathormone in...

Solutions To Exercises Lesson

The thyroid gland is in the neck region just below the larynx and surrounds the trachea. The masses on either side of the trachea are the right and left thyroid lobes. The tissue connecting the two lobes is called the isthmus. It is found across the front of the trachea. Each lobe of the thyroid gland is supplied by the superior and inferior thyroid arteries. The primary hormone of the thyroid gland is thyroxin, which affects the basal metabolic rate (BMR), the level of activity of the body. (paras 10-6--10-8)

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...

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.

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...

Surgical Harms Postoperative Complications

In addition to the complications described, the normal, uncomplicated course of events after a gastrectomy will include a number of expected but undesirable health consequences. The weakness and tiredness associated with any major surgery usually takes several months to resolve completely, and in the case of gastrectomy, this is further added to by the nutritional problems induced by removal of part or all of the stomach. Patients can expect to have a smaller appetite and small capacity, and to lose weight for some time after leaving hospital until they reach a stable metabolic state.

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...

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 (Seaberg 2005), a high rate of smoking among HIV patients and increased levels of tissue plasminogen 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 of...

Melanin Concentrating Hormone Receptors

Within the brain, high levels of MCHR1 mRNA have been found in areas that regulate food intake, olfaction, and motivated behavior, and expression levels increase upon fasting. In aggregate, these observations suggest a role for MCH, acting through MCHR1, in integration of taste, olfaction, and positive reward aspects of feeding behavior. MCH-transgenic mice are glucose intolerant, insulin resistant, and prone to weight gain on a standard chow diet.57 MCH-null mice are mildly hypophagic and lean and exhibit increased oxygen consumption and metabolic rate, reduced fat stores, and resistance to diet-induced obesity.58 Data for MCHRl-null mice59,60 are largely consistent with the phenotypic analysis of mice lacking the MCH ligand, although MCHR1-knockout mice are mildly hyperphagic on normal chow, suggesting they maintain lean body mass via increased basal metabolic rate.

Nutrient Sensing Receptors

(GPR40) and short-chain carboxylic acids (GPR41 and GPR43).168-171 Long-chain fatty acids serve as energy sources and also have the potential to be converted to signaling molecules within cells. Excess long-chain fatty acids are known to induce insulin resistance and contribute to metabolic derangements in diabetes and obesity.172 The identification of fatty acid receptors presents the intriguing possibility that some of the recognized metabolic effects of circulating free fatty acids may occur via these GPCRs.

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).

Assessing Response to Therapy

Patient Show Report Graph

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...

Background And Relevant Pharmacokinetics

One of the two fats identified as being essential for humans to consume is alpha-linolenic acid (ALA or 18 3n-3) which, due to the position of its first double bond, is classified as an omega-3 essential fatty acid (n-3 EFA). Although mammals have the ability to introduce double bonds into most positions of the fatty acid chain in fat metabolism, therefore creating a variety of unsaturated metabolites, they lack the capacity to insert double bonds at the n-3 and n-6 position. Consequently, linoleic acid (LA) and alpha-linolenic acid (ALA), which already have the double bond at the n-3 or n-6 position, respectively, are considered essential and must be consumed in the diet. When the EFAs are consumed in this precursor state they follow a pathway of further elongation and desaturation via the action of delta-6- and delta-5-desaturase until they form the 'active' fatty acids eicosapentaenoic acid (20 5 n-3) (EPA) and docosahexaenoic acid (DHA) (22 6 n-3).

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...

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...

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

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...

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.

Growth Hormone Gh And Somatomedins Igfs

Here it is shown that GH is released through the action of hypothalamic growth hormone-releasing hormone (GRH), as described earlier in Chapter 3. The GH released into circulation has two effects One effect is to directly act on lipid and fat metabolism, analogously to Cortisol action, in a manner to oppose the actions of insulin and IGF-I, as shown by its ability to directly increase blood sugar (Figure 19-1). The other action of GH is on liver and other organs to generate IGF-I, which, like insulin, produces skeletal growth as well as tissue growth. IGF-I is active as a negative feedback agent on the hypothalamus and causes the production of somatostatin (GIH), which inhibits the release of GH from the anterior pituitary, and it also acts at the level of the pituitary to inhibit expression of the GH gene in response to GRH. When GH causes IGF-I to be produced, IGF-I-binding proteins are also synthesized in the liver and other tissues, and both IGF-I and binding proteins are secreted...

Receptor Gene Polymorphisms

Most human GPCR polymorphisms appear as functionally neutral however, several affect either gene expression (and thus protein abundance) or the structural and functional properties of the encoded protein. Altered abundance or function may be associated with a clinical phenotype. Cardiovascular diseases typically have multifactorial etiologies and result from the synergism of several genes interacting in a complex way with environmental and life style factors. Epidemiological studies have investigated several candidate genes encoding proteins contributing to the control of blood pressure, lipid and energy metabolism, and cardiovascular function, and thus possibly associated with human atherosclerosis, hyperlipidemia, hypertension, and myocardial infarction.

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...

The Exercise Prescription

To promote the message of increased activity for all Americans, the American College of Sports Medicine (ACSM) and the Centers for Disease Control (CDC) have recommended that every adult should accumulate 30 min or more of moderate-intensity physical activity on most, preferably all, days of the week (35). Moderate activity in this recommendation is defined as activity that elicits an energy expenditure of three to six times resting metabolic rate (3-6 METS). In layman's terms, this means simple activities such as walking, gardening, playing golf, walking the dog as well as incorporating more activity into one's lifestyle, like using the stairs instead of the elevator, parking the car at the far end of the lot, etc. Those who follow these recommendations for activity will experience many of the health-related benefits of physical activity (Table 1), but they may not improve their fitness level (35).

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...

T Imaging of Brain Tumours

Proton MR spectroscopic imaging ('H-MRSI) is a non-invasive technique that provides metabolic information from living tissues 3, 4 . Of the main metabolites of interest, choline (Cho) is found to be increased in areas of active membrane turnover, as in brain gliomas N-acetylaspartate (NAA) is regarded as a marker of neuronal damage, destruction and or dysfunction, and it is decreased whenever neurons are replaced by other cells creatine (Cr) comprises signals from both phosphocreatine and creatine and is involved in energy metabolism and lactate and or lipids (LL) usually indicate necrosis 3, 4 . Several studies have demonstrated that 1H-MRSI can be used to guide surgical resection or biopsies, to define radiotherapy planning and monitor treatment effects, and to identify recurrence and progression of brain gliomas 3-10 .

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...

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...

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

Biological And Molecular Actions

Thyroid hormones produce a wide array of physiological effects in virtually all of the body's organs and metabolic pathways these are summarized in Table 64. Principal effects include the modulation of oxygen consumption, as well as carbohydrate, protein, and fat metabolism. In addition, thyroid hormones modulate the degradation and synthesis rates of many other growth factors and hormones, which results in many secondary effects. The biological effects of thyroid hormone are divisible into two general categories

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.

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...

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).

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.

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.

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.

Deregulation Of Apoptotic Pathways In Brain Tumors

In established malignant gliomas, there is also extensive cell death. However, the type of cell death in these tumors is predominantly necrotic 11 . Central fields of necrosis which are prominent in the primary type of glioblastoma 12 can be distinguished from small foci of necrosis often surrounded by pseudopalisading tumor cells. Yet, apoptosis does also occur in malignant gliomas on the basis of light microscopic and ultrastructural criteria, including nuclear condensation and pyknosis and formation of apoptotic bodies, and by in situ detection of DNA fragmentation using in situ terminal transferase-mediated dUTP nick end labeling (TUNEL) 13 . TUNEL-positive tumor cells are preferentially located among these perinecrotic pseudopalisading cells 13,14 . Hence, specific properties of the microenvironment may account for the induction of the different types of cell death. In particular, gradients of tumor hypoxia combined with reduced supply of nutrients, such as glucose and amino...

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.

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)....

Molecular Subsets of Brain Tumors

DNA microarray analyses have shown that different subtypes of gliomas have distinct gene-expression profiles, which can be distinguished from one another and from normal tissue 82-86 . Specifically, these differences involve pathways crucial to cell proliferation, energy metabolism, and signal transduction 86 . The genetic profile of low grade astrocytomas shows most frequently alterations in p53 expression and in loss of heterozygosity on chromosome 17, which

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.

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...

Linearization Approaches

A number of graphical techniques that aim at transforming the measured data into a plot which is linear after a certain transformed time have been proposed for specific tracer studies, including the Patlak 75,76 , Logan 77, 72 , and Yokoi 78, 79 plots. Applications of the techniques depend on the tracer studies and parameter of interest. The Patlak plot 75 was initially developed for estimating the influx rate constant of radiotracer accumulation in an irreversible compartment, and was extended to allow for slow clearance from the irreversible compartment 76 . When employed in FDG studies, the influx rate constant is directly proportional to the regional metabolic rate of glucose. The Logan plot 77, 72 was primarily developed for estimation of parameters related to receptor density such as binding potential and volume of distribution for neuroreceptor studies and the radiotracers can have reversible uptake. The Yokoi plot 78, 79 has been proposed as a rapid algorithm for cerebral...

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.

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).

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...

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...

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.

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).

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.

Spectroscopy Basics

Tions and have the appropriate physical configuration to be detected by MRS. Besides the technical prerequisites, 'H and 31P are prominent candidates for clinical studies also from a biochemical viewpoint, as they allow in vivo investigation of some of the processes involved in brain metabolism. For instance, 31P-MRS has been the first to be applied to medicine in vivo, and can be used to evaluate brain energy metabolism by directly and non-invasively measuring ATP, PCr or Pi concentrations. While 31P-MRS was the first spectroscopic technique to be applied in vivo, the main nucleus studied today in neuospectroscopy is *H, which provides information on markers of neurons, myelin, energy metabolism and other metabolically active compounds. Besides its important clinical role, 1H spectroscopy is also less technically demanding as it uses hardware employed for standard MRI, and provides a higher signal noise ratio (SNR) 1, 3 .

Ergogenic

While initial animal studies showed promise, recent randomised, controlled clinical trials have produced inconsistent results in healthy individuals and athletes (Eschbach et al 2000, Dowling et al 1996, Mahady et al 2000) and a recent review concluded that only poorer quality trials have demonstrated benefit while well-designed trials have not shown significant improvement in endurance performance, cardiorespiratory fitness, or fat metabolism during exercise ranging in duration from 6 to 120 minutes (Goulet & Dionne 2005).

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...

Ecology

Are Hippopotamus Are Endotherms

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...

PTK Subfamilies

The three members of the insulin receptor family are disulfide-bonded dimers that undergo cleavage during processing to generate a- and P-subunits. In addition to the well-known metabolic effects mediated by the insulin receptor, this family mediates important survival signals.

Species accounts

Reproduction Biology

In host intestine influenced by nature of lipids in host diet. Specific amino acids readily taken up and catabolized role in energy metabolism still unclear. Site of absorption of amino acids unknown. Both uridine and thymine transported from host lumen but nucleoside transport mechanism not known.

Porphyrias

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...

Cortisol

Cortisol (hydrocortisone) is a glucocorticoid, which means it affects glucose metabolism. It is produced in the middle zone (zona fasciculata) of the adrenal cortex and has a molecular structure similar to aldosterone (fig. 13.30). In addition to affecting glucose, cortisol influences protein and fat metabolism. Among the more important actions of cortisol are the following

Ure 2325

Decreased metabolic rate reduced ability to cope with stress reduced ability to maintain homeostasis Degenerative changes in cardiac muscle decrease in lumen diameters of arteries and arterioles Decreased cardiac output increased resistance to blood flow increased blood pressure Decrease in efficiency of immune system

Challenges

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

Ginseng And Diabetes

Such rapid liquid excretion leads in turn to the characteristic thirst of diabetics. Lack of insulin may also be due to autoimmune damage to the islets of Langerhans. In diabetic patients protein and fat metabolism is enhanced with the breakdown of tissue proteins, lipids and fatty acids and the resultant occurrence of nitrogenous and ketone compounds in urine. Overweight persons are more prone to diabetes and have a shorter life expectancy. Complications of untreated diabetes include cataracts and blindness, ketoacidosis (high urinary ketone levels), gangrene of the feet, heart disorders, aetherosclerosis and renal failure.

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.

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...

Clinical Aspects

In prolonged starvation, as adipose tissue reserves are depleted there is a very considerable increase in the net rate of protein catabolism to provide amino acids not only as substrates for gluconeogenesis but also as the main metabolic fuel of the tissues. Death results when essential tissue proteins are catabolized beyond the point at which they can sustain this metabolic drain. In patients with cachexia as a result of release of cytokines in response to tumors and a number of other pathologic conditions, there is an increase in the rate of tissue protein catabolism as well as a considerably increased metabolic rate, resulting in a state of advanced starvation. Again, death results when essential tissue proteins have been catabolized.

Appetite Suppressant

Synephrine produces effects on human metabolism, which could be useful for reducing fat mass in obese humans because it stimulates lipolysis, raises metabolic rate and fat oxidation through increased thermogenesis (Pellati et al 2002). A controlled in vivo study of C. aurantium fruit hydro-alcoholic extracts standardised to synephrine 4 (Ci.au. 4 ) and 6 (Ci.au. 6 ) found repeated administration of the extract significantly and dose-dependently reduced food intake and body weight gain (Calapai et al 1999).

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...

Back To Mitochondria

On the other hand, there is abundant evidence that multiple cellular defense systems can be upregulated in concert, to increase stress resistance and survival in a diverse range of organisms (Tatar et al., 2003). This is exemplified by the identification of a wealth of mutants in nematodes, flies, and mice, downregulating pathways of growth, reproduction, and energy metabolism, resulting in significant increases in life span as well as increased stress resistance, including resistance to oxidative stress. We do not know if in all these mutants, in different

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