Natural Metabolism Boosters

Cinderalla Solution

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Proof That Mouse and Human Metabolism and Biodistribution Is Similar

Isolation Mice Hepatocytes

To apply the information obtained in the knockout mice to humans, mouse and human metabolism were compared using hepatocytes 54 . To this end, the metabolic profile of FP-TZTP was studied in rat and human hepatocytes using liquid chromatography and mass spectrometry and, when possible, compared with independently synthesised standards. In both human and rat hepatocytes, the major metabolite results from oxidation of the nitrogen in the 1-methyltetrahydropy-ridine ring. Other metabolites result from sulfur oxidation, demethylation of the tertiary amine and oxidation of the tetrahydropyridine ring. The metabolism of FP-TZTP in vivo in rats is similar to that obtained in rat hepatocytes. From our knowledge of the structure of the metabolites, we have developed a two-step extraction sequence that allows the isolation of unmetab-olized parent compound. This method allows rapid determination of the parent fraction in plasma and does not require time-consuming chromatographic analysis.

IRS Molecules Participate in GH Signaling

A possible mechanism to account for some of the insulinomimetic and insulin-antagonistic metabolic effects of GH. Further, GH-induced lipid synthesis and GH's inhibition of noradrenaline-induced lipoly-sis in rat adipocytes are blocked by the PI-3-kinase inhibitor wortmannin. It is uncertain whether the requirement for GHR tyrosine residues 333 and or 338 (which are phosphorylated in GH-treated cells) for GH-induced lipogenesis and protein synthesis is related to the activation of IRS-1 and or IRS-2. While IRS proteins may have a role in potentiating GH-induced metabolic effects (given their likely importance in insulin-induced metabolic signaling), studies employing PI-3-kinase inhibitors and a dominantnegative form of the PI-3-kinase p85 subunit suggest that PI-3-kinase may not be involved in GH-mediated glucose transport in 3T3-L1 adipocytes. Thus, the linkage of IRS-1 and -2 to this important metabolic effect of GH is brought into question. Recently, however, IRS-1 has been...

Oral Contraceptives and Progestins

The metabolic effects of oral contraceptives have raised some concerns about the use of these agents in insulin resistant women. Some but not all studies indicate worsening of insulin resistance in PCOS women on oral contraceptives. They have not, however, been shown to increase the rate of type 2 diabetes. Effects of oral contraceptives on vascular reactivity and inflammation in PCOS are yet not well studied, and it should be recognized that there may be potential adverse effects when considering these agents for PCOS treatment.

Regulatory Genes and Intracellular Signaling

Another interesting insight into the regulation of senescence comes from ore4-1. This mutation inhibits leaf senescence, yellowing, and death, and reduces the leaf growth rate (Woo et al., 2002). Interestingly, the mutation delayed natural leaf senescence but not hormone or dark-induced senescence. The ore4-1 mutant has a partial lesion in the chloroplast function including the function of photosystem I, which resulted from reduced expression of the plastid ribosomal protein small subunit 17 (PRPS17) gene. It is conceivable that the delayed leaf senescence phenotype observed in the ore4-1 mutant is due to reduced metabolic rate, since the chloroplasts, a major energy source for plant growth through photosynthesis, are only partially functioning in the mutant. This interpretation is consistent with findings that metabolic rate is one of the key mechanisms involved in animal aging, although further evidence is needed.

Species differences in metabolism

Differences in metabolism between species may be either quantitative or qualitative, but quantitative differences are more common. In general small animals such as mice metabolize foreign compounds at a faster rate than larger animals such as humans, consistent with differences in overall metabolic rate. An extreme example of a difference in rates of metabolism is afforded by the drug oxyphenbutazone. In the dog it is rapidly metabolized and has a half-life of around 30 min, in several other species such as the rat, rabbit and monkey the half-life is between 3 and 6 h, whereas in humans metabolism is very slow and therefore the drug has a half-life of about 3 days. Quantitative differences also exist although with a few exceptions, it is generally difficult to discern useful patterns. Even the simplest organisms such as bacteria seem to be able to carry out many different types of reaction. The differences which are clear and fall within taxonomic groups are mainly found with phase 2...

The Mitochondrial Death Pathway

Abstract Mitochondria have long been known to be critical for cell survival due to their role in energy metabolism. However, not until the mid-1990s did it become evident that mitochondria are also active participants in programmed cell death (PCD). This chapter focuses mainly on the role the mitochondria in mammalian cell death and cancer progression and therapy.

Approaches to Values for Children

In spite of the significant progress in research related to human nutritional needs, data were not usually available with multiple levels of nutrient intake to directly determine nutrient requirements for each gender and life-stage group, including children. Thus available data from other subgroups were extrapolated to develop EARs, AIs, and ULs for each subgroup (each DRI report discusses extrapolation methodologies employed for nutrients included in the report). Nutrients involved in energy metabolism were extrapolated on the basis of metabolic body weight (B.Wt.3 4). Extrapolation based directly on body weight was used for nutrients involved in bone maintenance and growth. The size of compartment or tissue weight was used as the basis for extrapolation for nutrients primarily distributed in the water space or other specific tissues.

Energy and Physical Activity

The DRIs include estimated energy expenditure at four levels of physical activity. Previous energy allowances were based on estimated time spent in various activities in addition to measured or predicted basal metabolic rates 3 . Rather than provide an RDA (a level of energy intake that would be adequate for almost all the population), an estimated energy requirement (EER) is predicted from regression equations derived from doubly labeled water data based on gender, age, weight, height, and four levels of physical activity (sedentary, low active, active, very active) 11 .

Singlescan Techniques

Another example of single-scan, model-based techniques is the autoradiographic method for measurement of glucose metabolism, which was developed in rats with 14C deoxyglucose 1 and extended to PET using 18F 2-fluoro-2-deoxy-D-glucose 2-4 . These methods take advantage of the fact that most of the radioactivity in the tissue by 45 min post-injection has been phosphorylated, so that the total tissue radioactivity can be used to estimate the net flux into tissue of deoxyglucose, K. This is the same rate constant as determined from the slope of the Patlak plot. Effectively, these methods estimate the slope of a Patlak plot by using the measured tissue value at one data point and by using population values of the model rate constants to estimate the y-intercept of the straight line. A number of other formulations of this approach have been developed 131-133 , each with different sensitivities to errors in the assumed rate constants. Finally, since FDG is an analog of glucose, the metabolic...

Hypothalamicpituitarythyroid Axis Components and Function

Iodine-containing compounds serve as global regulators of the body's metabolic rate, and are also critical for brain development. The release and synthesis of these hormones is ultimately controlled by signals from the CNS. Upon stimulation by TSH, the thyroid gland releases the iodinated amino acids T3 and T4. Of the two hormones, T3 is much more physiologically active. Although debate still exists in the literature, T4 is often considered a prohormone that becomes active after monodeiodination in peripheral tissues. T3 directly promotes gene expression through binding to thyroid response elements (TREs) located in the promoter regions of a diverse number of genes. T3 also directly regulates the HPT axis by inhibiting TSH release and gene expression in the pituitary, and TRH gene expression in the hypothalamus 3 . This is characteristic of the end-product negative feedback seen in the hypothalamic-pituitary-end organ axes. In the circulation, these hormones are primarily bound to a...

Formation and Metabolism of DHT in Cancerous Prostate

In 1965, Shimazaki et al. first found that incubation of radiolabled testosterone with tissue extracts of rat prostate or minced tissues of normal and pathological human prostates formed radiolabled DHT and androst-4-ene-3,17-dione.20'21 Three years later, Bruchovsky and Wilson found that DHT could be detected in isolated prostatic nuclei 2 hours after administration of 3H-testosterone to rats.22 Several months later, Anderson and Liao confirmed that nuclei of both rat ventral prostate and seminal vesicles selectively retained 3H-DHT.23 The metabolic rate of DHT formation is high in hyperplastic tissues, moderate in normal tissues, and low in cancerous tissues.20'21 Reduced activity of 5a-reductase in the cancerous tissues was further confirmed by various procedures incubation with minced tissues24 and with homogenate,25'26 RT-PCR,11'27 and microarray.10 Poorly differentiated cancerous tissues showed less activity than well differentiated ones. Metabolic foci in lymph nodes revealed...

Targeting and Activation of the Permeability Transition Pore

Membrane permeability transition pore complex (PTPC) (Brenner et al., 2003 Costantini et al., 2000 Debatin et al., 2002 Fantin and Leder, 2006 Galluzzi et al., 2006 Khosravi-Far and Esposti, 2004 Morisaki and Katano, 2003 Reed, 2004). Additionally, alterations in energy metabolism, such as depletions in ADP and ATP, can also facilitate formation of the PTPC.

N System Theories of Aging Rateof Living

The rate-of-living hypothesis of aging states that the metabolic rate of a species is inversely proportional to its life expectancy (Chapter 3). The original theory makes two predictions (36) including the following 2. There is an inverse relationship between metabolic rate and aging. Recent data show that the metabolic potential does not stay at a constant value for different populations of a species (36). Long-lived strains spend about the same number of calories per day yet, they may live significantly longer. Thus, during their life time, the long-lived strains expend around 40 more calories than the normal-lived strains (36).

Doseresponse Modeling

Frequently, however, such models do not exist. In these cases, there are a variety of simple scaling relationships available for inferring equivalent human doses from animal doses, although there is considerable debate as to which relationship is most generally appropriate. The simplest relationship is based on body weight scaling. Early studies indicated that the LD50 was approximately equal in humans and animals when the mass of contaminant taken into the body was divided by the body weight. This observation led to the traditional chemical dose unit of mass of contaminant per unit body weight (BW), which is typically expressed in units of mg kg (Dedrick 1973 Rhomberg and Wolff 1998). However, this relationship does not always hold true. The LD50 values are frequently found to be more nearly equal among species when a relationship based on body surface area is used. A mass scaled dose (in mg kg) can be converted to a surface area scaled dose by noting that surface area is...

Short Term Intake Regulation

In anticipation of their metabolic effects by release of peptide hormones to different organs involved in the processing of the nutrients derived from digestion and absorption 7 . Whereas long-term food intake is controlled by adiposity signals, the regulation of short-term food intake is dictated mainly by food signals arising from both their preabsorptive action in the gut and their postabsorptive metabolism.

Structure And Function Of The Pulmonary System

The major function of the pulmonary system is the oxygenation of blood and the removal of carbon dioxide from the body. Breathing ventilates the respiratory tissue leading to gaseous exchange in the lungs. The tissue is therefore specialized to present the largest available surface area within the protection of the thoracic cavity. The large oxygen requirement is necessary to support the high metabolic rate of mammals.

Neurodegenerative Disorders

Categories structural proteins, energy metabolism, protein synthesis, protein degradation, RNA transcription, chaperones, oxidative stress response, signal transduction and synaptic proteins. However, it is likely that the 2-DE analysis of total extracts from whole brain or brain compartments led mainly to the detection of high-abundance proteins. Furthermore, the proteins identified were derived from various cell types neurons, astrocytes, oligodendrocytes, microglia, blood vessel walls and blood cells. AD is the major dementia affecting the elderly thus, it is logical to find a large number of proteomic studies devoted to the investigation of this disease (Butterfield et al. 2003). Proteomic analyses of different brain regions from AD patients and non-demented controls led to the identification of various proteins with altered expression levels. These changes in protein expression reflect the cascade of alterations on multiple pathways within the brain of AD patients decreased...

Future Development for Improving the Protein Quality in Infant Formula

Which have physiological relevance beyond purely nutritional properties 41 . These factors are implicated in growth and development, protective defense mechanisms, energy metabolism and immune homeostasis in multiple tissues. Despite the improvement in infant formula development, differences in response to infection and the development of allergy and atopic disease have been reported for FF and BF infants 42 . Although some of these bioactive proteins are also present in bovine milk 41 , it has generally been assumed that they do not survive the technological processing used in the manufacture of infant formulas. As such, infant formulas are considered to lack some of the protective factors which human milk inherently provides.

Directed fetal placental signals and fetal placental maternal interactions

We believe that of the placental hormones listed, leptin holds special promise as one of the putative signals to modify maternal and placental function to augment nutrient delivery. Leptin has numerous effects to alter energy metabolism and influence adiposity (Harris, 2000). Many of these are quite relevant to the metabolic adaptations of pregnancy that are accentuated in pre-eclampsia. Leptin acts Leptin has effects in several tissues to modify energy metabolism and uptake in the placenta leptin can increase amino acid uptake. Leptin is produced by the placenta and increased by hypoxia, as might be expected in placental and fetal tissues with poor placental perfusion. In keeping with the effect of hypoxia, leptin is increased in the blood of women with pre-eclampsia and in the placentas from these pregnancies (McCarthy et al., 1999 Mise et al., 1998 Teppa et al., 2000). Paradoxically and consistent with a fetal signal not expressed in response to reduced nutrient and oxygen delivery...

Target Organ Toxicity

Thus, the distribution of the parent compound or metabolite(s) into the target tissue(s), metabolism and excretion in such tissues and the interaction with receptors or other critical cellular macromolecules are all dynamic processes occurring at particular rates. Factors which affect these processes therefore will influence toxicity and the particular target organ, and may even change the target organ. Thus, it is clear from figure 6.1 that if the parent compound is toxic, factors such as enzyme induction or inhibition which change metabolism (m) or change distribution to tissues (d) or excretion (e) will tend to change the toxicity. This is provided that the toxic response is dose-related. Specific uptake systems will influence the distribution (d) and specific excretory routes (e) may be saturated. Metabolism may cause the appearance of another, different, type of toxicity. If a metabolite is toxic then factors which increase metabolism may increase the toxicity, provided that...

Calmodulin Action in Cells

Insulin Secretion

Generation of calmod-ulin mutant proteins has also been used successfully to assess specific functions of calmodulin in vitro and in vivo. As mentioned previously, the two globular ends of calmodulin that contain the pairs of Ca2+ binding sites are separated by a long central helix. The flexibility of this helix is essential for calmodulin to properly associate with its various target proteins to ensure a biological response. When the central helix is shortened by eight amino acids, a protein is produced that binds Ca2+ identically to the authentic calmodulin but cannot bind to or activate a variety of calmodulin-dependent enzymes. Such a mutant can be used to differentiate between the effects of calmod-ulin as a regulator of target proteins and as a Ca2+ binding protein (Fig. 8). Creation of transgenic mice that overexpress calmodulin in the pancreatic P cells results in an early onset, nonimmune diabetes. Although the pancreas contains plenty of insulin,...

Phagocytosis and sequestration

In the presence of metabolically active macrophages, the densely packed red cells are deprived of oxygen and glucose. This stress increases membrane rigidity and reduces the natural deformability of the biconcave cell. This occurs especially as a result of excessive reaction to stress (e.g. because of an underlying abnormality of the red cell metabolic system, or because the cells are already spherical or antibody coated, or are fragmented or misshapen in other ways) they remain trapped in the cord space and there undergo phagocytosis.

Iodine deficiency disorders IDD

Iodine is needed to make thyroid hormones so prolonged iodine deficiency impairs thyroid function resulting in lower metabolic rate, lethargy, growth retardation and brain damage. Goitre occurs when the thyroid gland enlarges in an effort to capture more iodine from the blood.

Consequences of Deficit and Excess Energy Intake

Deficit energy intake and negative energy balance can be acute or chronic 9 . Acute energy deficiency results in short-term negative energy balance during which there is a progressive loss of body weight. Chronic energy deficiency reflects long-term inadequate food intake during which a steady state is achieved at a suboptimal nutritional status. Energy deficit in children leads to growth retardation, loss of fat and muscle, delayed motor, cognitive and behavioral development, diminished immunocompetence, and increased morbidity and mortality 10 . Adaptations in metabolic rate and physical activity in response to chronic energy deficiency in children are difficult to assess for technical problems and mitigating geographical and social circumstances. The functional and behavioral consequences of energy deficiency are responsive to food supplementation. Food policies and nutrition programs aimed at meeting the energy requirements of children are clearly warranted, but their...

Factors Affecting Toxicity Pharmacokinetics and Pharmacodynamics Pharmacokinetic Models The chemical absorbed dose is a fraction of the chemical administered dose. This fraction can be highly variable, being a function of the individual, the chemical and physical form of the contaminant, the pathway through which the chemical enters the body (e.g., ingestion, inhalation, or dermal exposure), and the person's age and diet. Determination of the chemical effective dose as a function of the chemical absorbed dose involves another layer of complexity. The effective dose is a function of both the total administered dose and the dose rate and the route of exposure, as shown in Figure 11.1. Determination of absorbed and effective doses on the basis of an administered or applied dose can be accomplished with a pharmacokinetic model that tracks the absorption, distribution, metabolism, and elimination of chemicals. These models are typically compartmental models of contaminant transport in humans and animals. The compartments can be defined...

Metabolically Resistant THRCs

Many crops bearing transgenes coding for highly specific enzymes that metabolically catabolize herbicides have been generated (Cole and Rodgers, 2000). These include, for example, bromoxynil resistance crops bearing a nitrilase (Stalker et al., 1996), glufosinate resistance crops bearing an ace-tyltransferase (Vasil, 1996), 2,4-D-resisting crops bearing a highly specific soluble cytochrome P-450 monooxygenase (Streber and Willmitzer, 1989) phenmidipham-resisting crops bearing a bacterial gene (Streber et al., 1994), and dalapon-resisting crops bearing a dehalogenase (Buchanan-Wollaston et al., 1992). Of these, only the bromoxynil- and glufosinate-resistant crops have reached commercialization. All of the genes used commercially are of bacterial or actinomycete origin, despite the fact that plants contain genes for herbicide resistance, which is the basis for most natural metabolic selec-tivities used for 45 years. Nevertheless, plant genes conferring metabolic resistance have not yet...

Methods applications and concepts of metabolite profiling Secondary metabolism

Glufosinate Metabolism

A proposed mechanistic model of the metabolic response ofMedicago truncatula cell suspension cultures to methyl jasmonate elicitation 39 . The data suggest a major reprogramming of metabolism in which as carbon normally destined for sucrose is redirected towards secondary metabolism (triterpene saponin). Figure 1. A proposed mechanistic model of the metabolic response ofMedicago truncatula cell suspension cultures to methyl jasmonate elicitation 39 . The data suggest a major reprogramming of metabolism in which as carbon normally destined for sucrose is redirected towards secondary metabolism (triterpene saponin).

Other defects of the enzymes of the glycolytic system

Acts as NLK, a lymphokine that induces the formation of antibody-secreting cells. It is also present in neutrophils, but there is no increase in infections in deficient subjects. In some severely deficient patients, neurological retardation has been thought to be related to hypoxia or ischaemia in utero rather than to direct metabolic effects.

Alternative Medicine and Female Infertility

Acupuncture is a vital therapeutic modality in traditional Chinese Medicine and its use can be traced back for centuries. The theory behind acupuncture is based upon the premise that there are patterns of energy flow, or Qi, through the body, which are essential for health. When a disease state exists, the flow of Qi is interrupted and its correction will assist in the healing process. Acupuncture can correct imbalances of flow at identifiable points close to the skin. The flow of Qi is based upon a meridian system of vital channels. The meridians consist of 20 channels interconnected by about 400 acupoints. These acupoints correspond to specific areas on the surface of the body, which demonstrate higher electrical conductance, thought to be due to the increased density of gap junctions along cell borders. These gap junctions serve as sinks, or converging points for electromagnetic fields. In addition, a higher metabolic rate, temperature, and calcium ion concentration are also...

Role Of Metabolic Activation

Thalidomide Rodent Rabbit

There is clear evidence from many different sources that the metabolism of compounds may be involved in their teratogenic effects, as will be seen in the final chapter in the discussion of thalidomide and diphenylhydantoin teratogenicity. The embryo and foetus of some species clearly have metabolic activity towards foreign compounds which may be inducible by other foreign compounds. Thus, foetal liver from primates has a more well-developed metabolic system for xenobiotics than does that from rodents and rabbits for example. This may be due to the late development of the smooth endoplasmic

Methods applications and concepts of metabolite profiling Primary metabolism

Thalidomide Rodent Rabbit

One strategy to dissect primary metabolic effects from secondary adaptations is the use of dose dependency. In environmental challenges different light intensities, temperatures or concentrations of nutrients and chemicals can be applied. In GMO studies stably modified lines with a range of low, medium to high transgene expression can be selected. Chemically controlled or otherwise inducible promoters can be employed for the same purpose. The use of these promoters may yield different metabolic responses compared to constitutive promoters and generate novel insights into metabolic regulation (e.g., 21 ). In all cases sensitive metabolic effects which respond to small doses can be distinguished from effects of high doses that are more prone to cause pleiotropic effects. Moreover, the dose quantity can be linked to a quantitative metabolic effect for example by application of correlation analysis. It can be argued that those metabolic effects which show a strict dose dependency have a...

The Eyes Optical Components Cornea

Human Power

Biochemical studies revealed a gradual decline in high-energy metabolism of the aging cornea as shown by linear decreases in phosphomonoesters, phosphocreatine, and ATP, accompanied by decreased inorganic orthophosphate (14). Corneal aging is accompanied by a linear loss of keratocytes paralleling loss in endothelial cell density (15). A three-dimensional expansion of collagen fibrils along the axial direction occurs in corneal stroma with aging. The expansion is due to decreased molecular tilting angle within fibrils. It reflects an increased number of fibrils due to expansion of intermolecular Bragg spacing caused by glycation-induced cross-linkages (16). Previously described morphological aging changes in cornea have been confirmed and better described. Human corneas become less symmetrical with age increased pupillary dilation and wavefront aberration become more pronounced with aging (17). Steepening of corneal curvature with aging, as shown by a decrease in vortex radius and an...

Head and Neck Tumours

The presence of lymph node spread of head and neck tumours is associated with substantially worse prognosis, and clinical examination and imaging techniques (CT and MRI) detect fewer than 50 of involved lymph nodes, which may result in unnecessary neck surgery. In patients with head and neck tumours studied prior to initial surgery, the sensitivity and specificity of 18F -FDG PET in detecting nodal metastases has been reported ranging from 71 to 91 , and 88-100 , respectively (Fig. 16.7) 8, 80-83 . Metastatic disease outside the neck can also be identified with 18F -FDG PET scans 84 . Primary tumours can also be detected with a similar sensitivity to CT MRI. In patients studied after initial treatment of metastatic nodal disease with radiotherapy, 18F -FDG PET is often accurate only after a three month period 20, 85-87 . This has been shown to be due to the effects of stunning of tumour cells, where the metabolic rate and proliferation of cancer cells may be suppressed after

Physiological Effects

Major analgesic which is responsible for many cases of therapeutic, accidental and intentional poisoning. Metabolized by hydrolysis to salicylic acid which is conjugated. Conjugation pathways are saturable so that the half-life increases with dosage. Therefore blood level of salicylate rises disproportionately with dosage. When salicylate enters tissues, it uncouples oxidative phosphorylation causing heat generation, increased cellular metabolism and production of carbon dioxide, increased requirement for oxygen, increased rate and depth of breathing via the effect on central respiratory control. This leads to metabolic alkalosis and overcompensation leads to metabolic acidosis. Acidosis allows more non-ionized salicylate to enter tissues including CNS, leading to more metabolic effects and greater acidosis and decreased urinary excretion. Effects on CNS may lead to death. Treatment involves alkaline diuresis, reduction of temperature, replacement of ions and glucose.

Metabolic Networks and Planetary Atmospheres

We may never know enough about the history of life and metabolism to distinguish between different ways in which metabolism might have grown. However, we can address the key prediction of many network growth models I discussed above. Are highly connected metabolites old metabolites The answer will contain a speculative element, because the oldest metabolites are those that arose in the earliest days of the living, close to life's origins. In addition, life forms as different as bacteria and humans have core metabolisms with a very similar structure. This suggests that the growth of metabolism has essentially been completed at the time the common ancestor of extant life emerged. Because this common ancestor does no longer exist, the detailed structure of its metabolism will remain in the dark forever. However, various hypotheses about life's origin make predictions on the chemical compounds expected to have been part of early organisms. There are several of these hypotheses, and they...

Maternal physiology in highaltitude pregnancy

Bell Palsy Causes Risk Factors

Maternal oxygen consumption increases by a minimum of 20 and carbon dioxide production by 25 in human pregnancy at sea level. This increase is accomplished by a 35 increase in ventilation, which in turn is due to increased tidal volume as opposed to breathing frequency. The increase in oxygen consumption is not just due to increased weight and metabolic rate at term oxygen consumption and carbon dioxide per kilogram of body weight are still 10 higher than in the non-pregnant condition (Moore et al., 1987). At least part of the increased drive to breathe stems from a general doubling of hypoxic ventilatory response. But, as with any normally distributed variable, there must be women at the upper and lower ends of the bell-shaped curve who have greater or lesser capacity for increasing their tidal volume and hence oxygen transport. Likewise, humans are remarkably variable in their ventilatory sensitivity to hypoxia and hypercarbia, and women with low responsiveness in pregnancy do not...

U The Adrenal Medulla

Hurricane Quadrants

Lipofuscin, and decreased catecholamine fluorescence. These structural changes are associated with dysfunction of body temperature, bowel motility, cardiovascular maintenance (also partly regulated by parasympathetic inputs), blood pressure, water and electrolyte distribution, and energy metabolism. Several studies indicate that basal sympathetic activity increases in some elderly individuals, and the increase may be associated with dysregulation of the ability of the sympathetic nervous system to respond to a variety of challenges (49,50). Under basal conditions, in humans, plasma levels and urinary excretion of E and NE are highly variable. With aging, these hormones may do the following

Components of Energy Requirements

Energy requirements during development can be partitioned into components of basal metabolism, thermogenesis, physical activity, and energy cost of growth. Basal metabolism is defined as that energy expended to maintain cellular and tissue processes fundamental to the organism. Energy is needed to maintain body temperature, support the minimal work of the heart and respiratory muscles, and supply energy to other tissues at rest. The basal metabolic rate (BMR) is measured under standard conditions defined as awake and supine in a fasting, relaxed state in a thermoneutral environment. The thermic effect of feeding (TEF) refers to the energy required for the ingestion and digestion of food and for the absorption, transport and utilization of nutrients. The TEF amounts to about 10 of the daily energy expenditure 3 . Thermoregulation can constitute an additional energy cost when exposed to temperatures below and above thermoneutrality however, clothing and behavior usually counteract such...

Metabolic Complications

Given the prevalence of increased metabolic abnormalities in women with PCOS, careful attention to assessment of the metabolic state is recommended. This includes assessment of glucose tolerance and lipid profiles even in young women with PCOS particularly if they are obese. Inquiry into symptoms of sleep apnea is also recommended.

Mitochondria and Cancer

Given the important roles mitochondria play in cellular energy metabolism, free radical formation and PCD, defects in mitochondrial function are suspected to contribute to the development and progression of cancer and to resistance to therapy (Bettaieb et al., 2003 Brenner et al., 2003 Costantini et al., 2000 Debatin et al., 2002 Hersey and Zhang, 2003 Jaattela, 2004 Kasibhatla and Tseng, 2003 Kim et al., 2004). Defective apoptosis is one of the hallmarks of tumorigenicity and is implicated in multiple stages of tumor progression (Burns and El-Deiry, 2003 Hanahan and Weinberg, 2000 Ozoren and El-Deiry, 2003). Furthermore, the ability of tumor cells to escape apoptosis plays a key role in promoting resistance to conventional chemotherapy and radiation therapy (Abe et al., 2000 Barnhart et al., 2004 Daniel et al., 2001 El-Deiry, 1997 Thompson, 1995 Zornig et al., 2001). A link between mitochondria and cancer progression was suggested over half a century ago when Warburg reported the...


Hypoglycaemia (blood glucose concentration 2.2mmol l or 40mg dl) is generally associated with quinine infusion in adults and is most often attributed to quinine-induced hyperinsulinaemia, although other mechanisms, such as the effect of circulating cytokines, are likely to be involved. In children, pretreatment of hypoglycaemia is important. It is present in 10-20 of African children on presentation with cerebral malaria and is associated with a poor prognosis (Newton et al., 1998). High parasitaemias contribute to hypoglycaemia and probably also to lactic acidosis. Parasites consume glucose at a rate of 70 times that of erythrocytes to generate energy from anaerobic glycolysis of glucose to lactic acid. Sick patients are also likely to have high levels of circulating cytokines, which also contribute to the abnormal metabolic state (White et al., 1983 Krishna et al., 1994).


Molecules up to 1200 Daltons can pass freely through the gaps but larger molecules cannot, suggesting a functioning pore size for the connecting channels of about 1.5 nm. Coupled cells share a variety of small molecules (such as inorganic ions, sugars, amino acids, nucleotides and vitamins) but do not share their macromolecules (proteins, nucleic acids and polysaccharides). ATP can pass between the cells, as can cyclic AMP, which mediates many types of hormonal control. Consequently, hormonal stimulation in just one or a few epithelial cells will initiate a metabolic response in many cells. Gap junctions close in the presence of high concentrations of Ca2+ ions, so that if a cell is damaged, the influx of extracellular calcium will seal the cell's gap junctions and prevent the leak extending through the tissue.


We have summarized a large literature that points to a role for cholesterol in PCa progression. The evidence for this conclusion arises from epidemiology studies suggesting that a Western diet can promote, and long-term treatment with cholesterol-lowering drugs can inhibit, PCa growth. These findings in humans are supported by an array of molecular biological studies that point to a role for membrane cholesterol in cell signaling mechanisms relevant to PCa progression. Much of the data in the literature can be interpreted through the paradigm of the lipid raft model (diagrammed in Fig. 3), in which cholesterol-rich domains serve to process biochemical signals for tumor cell survival, proliferation, and migration. This model also accounts for the descriptive findings discussed here that suggest that malignant growth and cancer progression coincide with local tissue alterations in fat metabolism, and in particular, accumulation of cholesterol in tumor cell membranes. Further study of...

Piglet Studies

We measured the energy expenditure of the portal-drained viscera of neonatal piglets by means of sodium bicarbonate labeled with 13C 8 . It appeared to be almost three times as high as could be expected on the basis of its weight. While some 12 of total body energy expenditure occurred within the portal-drained viscera, the weight of the portal-drained viscera accounted for only 4 of total body weight. This high energy expenditure reflects the rapid growth rate and high metabolic rate of these organs (especially the intestine).

Sleep And Fatigue

Sleep is essential for restoring the normal balance between the different parts of the central nervous system. During sleep, the body's physical functions are rested and some renewal takes place sympathetic nervous activity decreases and the muscular tone becomes almost nil the arterial blood pressure falls, the pulse rate decreases, the blood vessels in the skin dilate and the overall basal metabolic rate of the body falls by up to 20 . On average, most humans need physiologically about 8 h of sleep per night however, in modern society most adults report an average of 7-7.5 h sleep per night, with 75 reporting daytime sleepiness (Rosekind et al., 1994).

Systemic Effects

Tified as a rule of thumb , because significant exceptions are extant (DOE 1999) (1) high rate of cell division, (2) high cellular metabolic rate, (3) less differentiated cells, and (4) well-nourished cells. Application of this rule explains the high radio-sensitivity of red blood cell precursors, which have all four characteristics, and the low radiosensitivity of muscular and nerve cells, which have few or none. This variable radiosensitivity of different tissues is important in determining the overall consequences from exposure to radiation.

Hypobaric Hypoxia

Ease, physical activity and metabolic rate. The drop in partial pressure of oxygen at cabin altitudes of 8000 feet (2400 m) is sufficient to cause tissue hypoxia and the development of symptoms in patients with reduced car-diopulmonary reserve. The physiological response to this hypoxia is to increase ventilation, which leads to a reduction in alveolar carbon dioxide and a rise in alveolar oxygen tension. This is explained by the simplified alveolar gas equation

White Fat Depots

The initial characterization of SSAT-overexpressing mice revealed, in addition to hairlessness, practically a total lack of subcutaneous fat depots (7). Subsequently, we found that these animals also lacked visceral fat depots and thus were severely lipo-atrophic. In contrast to other lipoatrophic mouse models, SSAT transgenics did not show any triglyceride accumulation in nonadipose tissues and they fully retained insulin sensitivity (21). On fasting, the transgenic animals showed severely impaired ketogenesis, very low plasma leptin level, and significantly reduced triglyceride, glucose, and insulin levels. The transgenic animals also exhibited significantly elevated basal metabolic rate in comparison with the wild-type animals, indicating a greater expenditure of energy (21). It thus appears that generalized SSAT overexpression causes lipoatrophy, but also

Anatomic Networks

The hippocampal formation plays a central role in the retrieval of information from memory storage 233-235 . Recent PET studies have examined the response of the hippocampus to episodic memory retrieval 71 in patients with schizophrenia and demonstrated that basal metabolic activity is increased in the hippocampus at rest. The patients in this study showed a significantly higher basal metabolic rate in the hippocampal formation. Under the conditions of low recall, however, there was no change in cerebral blood flow to the hippocampus, while under high recall conditions there was a slight decrease. The fact that the baseline was much higher than in normal subjects suggests the possibility that a ceiling effect might have occurred in the subjects included in this study. An alternative possibility, however, is that the hippocampus of schizophrenics may have a disturbance in the relay of information along the trisynaptic pathway, one that belies the overall increase of activity detected...

GABA metabolism

Gaba Shunt Glutamate Tca

Degradative part of the shunt is GABA-T, which is present in both neurons and astrocytes and in many other organs than the brain (Schousboe et al., 1977a Wu et al., 1978 Larsson et al., 1985 Schousboe and Waagepetersen, 2007). This enzyme has been purified to homogeneity by several investigators and characterized with regard to Km values for the substrates GABA and a-ketogluta-rate (Schousboe et al., 1973, 1974 Cash et al., 1974 Bloch-Tardy et al., 1974 Maitre et al., 1975 John and Fowler, 1976). A high metabolic rate of conversion of GABA to CO2 in situ is compatible with the low Km values for both substrates (Machiyama et al., 1970 Yu and Hertz, 1983) and the fact that GABA-T is a mitochondrial enzyme associated with matrix (Schousboe et al., 1977b). It should be noted, however, that CO2 production per se does not represent a net degradation of the C-4 unit derived from GABA (Fig. 2). Complete oxidation of the carbon skeleton of GABA requires pyruvate recycling, i.e., conversion of...

Ethylene Glycol

Ethylene Glycol Metabolism

Enzyme alcohol dehydrogenase and herein lies the key to treatment of poisoning. The result of each of the metabolic steps is the production of NADH. The imbalance in the level of this in the body is adjusted by oxidation to NAD coupled to the production of lactate. There is thus an increase in the level of lactate and lactic acidosis may result. Also, the intermediate metabolites of ethylene glycol have metabolic effects such as the inhibition of oxidative phosphorylation,

Hannah R Cock

Mitochondria are ubiquitous intracellular organelles, whose primary function is the production of cellular energy in the form of adenosine triphospate (ATP) from food-derived fuels. Each mitochondrion (Fig. 1) consists of a double membrane-bound structure, with an internal matrix in which many metabolic systems involved in breaking down food fuels reside. These include the fatty acid fJ-oxidation enzymes, and those of the tricarboxylic cellular calcium homeostasis (Duchen, 2000), and possess several calcium transport systems (Nicholls, 1985). The concentration of free intracellular calcium is central to normal neuronal functioning, and in turn this has been shown to be critically dependent on functioning mitochondria, as well as secondarily on sodium calcium exchange (White and Reynolds, 1995). Intramitochondrial calcium levels also have important regulatory functions, including direct influence on enzymes of the TCA cycle and consequent metabolic rate, which will be further discussed...


Little is known regarding the catabolism of proteins that are either currently marketed or under investigation. The absence of suitable biological assays or other analytical methods for identifying and quanti-tating protein degradation products obviously limits evaluation of this catabolism. Similarly, the catabolism of mABs (in particular, the catabolism of the Ig molecule) is complex and not well understood (65). mAB catabolism reflects the basal metabolic rate of the body as well as the function of phagocytic cells monocytes, macrophages of the reticuloendothelial system (RES) . There is also a relationship between IgG concentration and catabolism that is specific for each IgG molecule the higher the IgG concentration, the shorter the survival time. To explain this characteristic of immunoglobulins, Brambell et al. (66) hypothesized, and Junghans and Anderson (67) have confirmed, that there is a specific, saturable receptor for each immunoglobulin that, when bound, protects the IgG...


The risk factors for pre-eclampsia (all except smoking) are similar to those for cardiovascular disease in later life. It is clear therefore that some women who go on to develop pre-eclampsia have pre-existing endothelial dysfunction. They are vulnerable to even a mild inflammatory stress or increased antiangiogenic response. The source of this anti-endothelial stress appears to be a poorly implanted placenta, but may also involve a hormone-induced metabolic state that is damaging to the endothelium. Further understanding of the clinical spectrum of pre-eclampsia will allow us to customize anti-pre-eclampsia prophylaxis according to maternal and possibly paternal phenotype.

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