Best Way To Speed Up Metabolism

The Metabolic Reboot

The Metabolic Reboot is a book with very simple 2 stage, flexible, lifestyle eating plan. This process not only helps you lose fat but also maintains your newly slimmed down weight. It is designed to provide you the best guide in getting your weight reduced easily. The Metabolic Reboot is an intermittent booster for fasting. This book is a reliable and efficient group fitness, nutrition and lifestyle method for parents, professionals and anyone who desires to lose weight. There's no substitute for hard work, but with this product, each step is straightforward, and you get to reach your goals with ease. It is intended for those who want to possess more energy even after shedding excess weight and fat in the body, boost their insulin sensitivity, while improving their overall health. Mike Whitfield tried experimenting with so many things and came out with this easy and brand new way to burn off unwanted chest, hip stomach and butt fat. Other benefits of this product is that it helps to assists in stopping your obsession about eating and dieting, prevent your metabolism process from crashing, and those other processes that people find it difficult to pass through in the process of trying to lose the excess fat. Continue reading...

The Metabolic Reboot Summary

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The Metabolic Reboot Review

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The problem with this approach is that your metabolism slows down to conserve energy and prepare for the famine it

So, if you go off the diet and return to your old eating habits without making any adjustments (like moderately increasing your exercise level), you're likely to gain weight faster because your metabolism has become accustomed to burning calories more slowly. If you try to diet again, the same situation will probably happen again when you stop. You might now weigh more than when you started you've become a yo-yo dieter, which means your weight goes up a bit after each loss of weight, hence the image of a yo-yo on a string.

Endocrine Metabolic Effects

Figure 23-1 Release mechanisms of the injury response. The primary mediators are afferent neural stimuli, humoral mediators (monokines e.g., interleukin, TNF ), arachidonic cascade metabolites, and plasma protease. Secondary factors are anxiety, pain, hemorrhage, fluid loss, and infection (endotoxin)fFrom Kehlet H Endocrine-metabolic effects. In Raj PP ed Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 188.) The modifying effect of regional anesthesia on the endocrine-metabolic response to surgery is variable and depends on the technique of regional anesthesia ( Fig. 23-2 ). Each technique is described. Figure 23-1 Release mechanisms of the injury response. The primary mediators are afferent neural stimuli, humoral mediators (monokines e.g., interleukin, TNF ), arachidonic cascade metabolites, and plasma protease. Secondary factors are anxiety, pain, hemorrhage, fluid loss, and infection (endotoxin)fFrom Kehlet H Endocrine-metabolic effects. In Raj...

Energy metabolism heat production and physical work

Assessment of the protection requirements in a cold environment requires information about the energy metabolism of the individual. Metabolic rate is related to the intensity of physical work and can be easily determined from measurements of oxygen consumption. Tables are readily available that allows its estimation during different types of activity (ISO-8996, 2004). With few exceptions the values for metabolic rate also indicate the level of metabolic heat production. In most types of muscular work the mechanical efficiency is negligible. Table 14.1 can be used for a rough estimation of the metabolic rate and associated heat production. Average metabolic rate (Wm2)

Weight Management Motorize Your Metabolism

I always make it clear to patients that while acupuncture can be good for improving your metabolism, it is no substitution for proper nutrition and exercise. Let's make that clear up front. Timing is everything A 30-40 minute vigorous workout in the morning can keep your metabolism churning throughout most of the day. Evening workouts may be more convenient, but going to bed shuts down most of the effect. > - Acu-points can curb food cravings and power your metabolism for better weight management.

Cellular pathology of ischemic stroke

Acute occlusion of a major brain artery causes a stereotyped sequel of morphological alterations which evolve over a protracted period and which depend on the topography, severity and duration of ischemia 31, 32 . The most sensitive brain cells are neurons, followed - in this order - by oligodendrocytes, astro-cytes and vascular cells. The most vulnerable brain regions are hippocampal subfield CA1, neocortical layers 3, 5 and 6, the outer segment of striate nucleus, and the Purkinje and basket cell layers of cerebellar cortex. If blood flow decreases below the threshold of energy metabolism, the primary pathology is necrosis of all cell elements, resulting in ischemic brain infarct. If ischemia is not severe enough to cause primary energy failure, or if it is of so short duration that energy metabolism recovers after reperfusion, a delayed type of cell death may evolve which exhibits

Do I Need an Anesthesia Specialist for My Child

Infants and small children have striking physiological differences that place them at much higher risk of anesthesia than the older child or adult. Infants and small children have substantially higher metabolic rates and oxygen demand. The infant has much smaller lung volumes, a smaller airway that is more prone to obstruction, and far less respiratory reserve. The infant airway is not only smaller but also anatomically different. The epiglottis is relatively large and floppy minor airway irritation or infection (croup, epiglottitis) may result in swelling that can cause dangerous narrowing or even closure of the airway. Infants are prone to

Biochemical pathways of ATP generation

The store of ATP is limited and must therefore be continuously replenished. Regeneration of ATP occurs through aerobic and anaerobic processes by which energy-rich chemical substances (carbohydrates, fat and phosphocreatine) are transformed into compounds with less stored energy (lactate, H2O, CO2 and creatine). This is achieved by sequences of chemical reactions by which part of the change in free energy is used for the synthesis of ATP through a reversal of reaction (1). The ATP-ADP cycle constitutes a basic feature of energy metabolism in all cells and is an intermediate between energy-utilizing and energy-consuming processes. Skeletal muscle is a unique tissue in terms of the large variation in energy turnover. Transition from rest to exercise involves a drastic increase in energy demand and the rate of ATP utilization can increase more than 100 times. This corresponds to a utilization of the whole muscle store of ATP in about 2-3 s. To maintain a constant muscle ATP...

Energy expenditure during exercise

Energy expenditure during exercise varies over a large range. From a basal metabolic rate (BMR) of approximately 290-340 kJ h in men and 240-260 kJ h in women energy expenditure may increase to 45000 kJ h during heavy exercise. Assuming a mechanical efficiency of around 20 , this permits 1000 kJ h of work to be performed 24 . During a 10-s bout of exercise more than 10 kJ of work may be performed by a highly trained athlete and during a i-min bout 40 kJ 25 . BMR basal metabolic rate (kJ 24 h)

Clinical applications of ACE inhibition

ACE inhibitors are generally tolerated well, with no rebound hypertension after stopping therapy and few metabolic effects. Symptomatic first-dose hypotension may occur, particularly in hypo-volaemic or sodium-depleted patients with high plasma renin concentrations. Symptomatic hypotension was more common with the higher doses originally used. ACE inhibitors have a synergistic effect with diuretics (which increase the activity of the renin-angiotensin system), but are less effective in patients taking NSAIDs.

Experimental Case Study

Functional imaging in a primate model provides insight into the distributed networks associated with changes in motor function. Autoradiography was performed on the macaque monkey after unilateral ablation of cortical areas 4 and 6 on the left. Partial recovery of the local cerebral metabolic rate for 14C-2-deoxygl ucose in a number of subcortical structures accompanied partial motor recovery.341 At 1 week, when the animal was hemiplegic, hypometabolism was found in the ipsilateral thalamus and the basal ganglia, structures that receive direct and indirect input from the motor cortex. Activity was diminished as well in the contralateral cerebellar cortex and, less so, in the thalamus and the bilateral brain stem and deep cerebellar nuclei. This hypometabolism was consistent with the unilateral and bilateral projections of the ablated cortex and with a decrease in transsynaptic activity. This deafferenta-tion remote from the lesion is a functional depression called diaschisis. At 8...

Choroid Plexus Preparations to Study Transport

The BCSFB is uniquely equipped to transfer a lot of fluid, hence it displays fast water permeation. Brisk CP blood flow, substantial Na+,K+-ATPase, and carbonic anhydrase activities, along with a rapid metabolic rate that reflects extensive transport and syntheses, all support voluminous CSF turnover. Fluid throughput across CP, when normalized for mass of tissue, is equivalent to glomerular filtration rate in the kidneys. Human CP secretes about 400,000 mL day. Efficient transfer of water across the BCSFB is assured by Aquaporin-1 (AQP-1), a channel conducive to the osmotic flow of water. Rapid and extensive permeation from blood into the CP-CSF system is demonstrated by kinetic analysis of uptake curves for tritiated-water, which penetrates the entire water compartment (extracellular plus intracellular) within minutes (31). This is consistent with water moving transcellularly through epithelial cells of CP.

NnnnnnnnnwN Fig3i ATPnd

Looking for significant metabolic reactions and for coenzyme-dependent ribo-zymes, the primary biological cofactor used in acyltransfer reactions, coenzyme A (CoA), has been the target of RNA pools leading to a 52-nucleotide minimal aptamer (Burke and Hoffmann, 1998) which recognizes the adenosine moiety of CoA and binds others ATP analogs (Fig. 3.10). The selection of coenzyme synthetase ribozymes is of particular interest in an RNA-catalyzed energy metabolism. Yarus, exploring the origin of ribonucleotide coenzymes, demonstrated the RNA-catalyzed formation of three common coenzymes CoA, NAD, and FAD from their precursors, 4'-phosphopantetheine, NMN, and FMN, respectively (Huang et al., 2000). A ribozyme capable of utilizing CoA for the synthesis of acyl-CoA was selected in vitro. The co-ribozyme isolated, that is an acyl-CoA synthetase, produced acetyl-CoA and butyryl-CoA (Jadhav and Yarus, 2002b).

Other Transport Systems Responsible for Drug Transport at the Blood Brain Barrier

Although it has not been established whether the Na+-dependent hexose transporter SGLT is expressed at the BBB, a recent report suggested a participation of SGLT in the BBB transport of cycasin (58). Cycasin, methylazoxy-methanol-d-glucoside, is proposed to be a significant etiologic factor for the prototypical neurodegenerative disorder Western Pacific amyotrophic lateral sclerosis and for Parkinsonism-dementia complex. Cycasin is taken up into primary-cultured bovine BCECs in a dose-dependent manner with maximal uptake at a concentration of 10 j.M. Since cycasin uptake was significantly inhibited by a-methyl-d-glucoside, a specific analogue for the Na+-dependent glucose transporter, SGLT, as well as by phlorizin (a SGLT inhibitor), replacement of extracellular NaCl with LiCl, and dinitrophenol (an inhibitor of energy metabolism), cycasin is suggested to be transported across the BBB via a Na+ energy-dependent SGLT (58).

Heat production in the cold

The hypothalamic temperature center receives inputs from skin cold receptors and projects them to the motor cortex and finally to the motor nerves. This leads to increased muscle tone and to oscillating contractions of muscles, shivering, that occurs mostly in trunk muscles. Shivering increases metabolic rates by 2-5 times the resting value. Due to the increased metabolic rate shivering should be avoided in winter sports. Meals increase heat production by a mechanism formerly called specific dynamic action, now diet-induced thermogenesis (DIT). The resting metabolic rate is increased about 10 for 1-2 h after a meal.

Gotta Have More and More

But the effect of most genes and their proteins are more subtle and do not produce an obvious or visible trait. Rather the proteins might help the brain function in several different ways by facilitating chemical neurotransmission in certain parts of the brain, by changing the number of synapses in certain places, or by changing energy metabolism. The point is that proteins determine how the brain (and the individual) functions or at what level it functions. A major reason why protein levels change is because of changes in the activity of genes or in gene expression. Changing gene expression ultimately has an effect somehow, somewhere. And, as we have said, drugs of abuse cause changes in gene expression that, in the end, result in a behavioral state characterized by the urge to find and take more drugs

Imaging of Other Neurotransmitter Systems

Baxter LR, Jr, Schwartz JM, Mazziotta JC, et al. (1988). Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder. Am J Psychiatry 145 1560-1563. Baxter LR, Jr, Schwartz JM, Bergman KS, et al. (1992). Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 49 681-689. Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM (1990). Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry 47 840-848. Guich SM, Buchsbaum MS, Burgwald L, et al. (1989). Effect of attention on frontal distribution of delta activity and cerebral metabolic rate in schizophrenia. Schizophr Res 2 439-448. Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM (1989). Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology 2 23 -28. Schwartz JM, Stoessel PW, Baxter LR, Jr, Martin...

How does magnet therapy work

In theory, the application of a magnetic field increases blood flow by acting on calcium channels located in vascular muscle. Increased circulation improves tissue oxygenation with subsequent elimination of inflammatory byproducts that elicit pain. Magnets also may influence the metabolism and energy flow in both positive and negative ways. The positive magnetic pole is thought to decrease the metabolic rate (negative effect), whereas the negative pole normalizes the body's metabolic and energy function (beneficial effect). In addition, a membrane-stabilizing effect on nociceptive fibers may occur, rendering these fibers less excitable and reducing the firing frequency of unmyelinated C fibers. Research findings do not support claims regarding efficacy of magnetic therapy.

Opioids Ketamine and Benzodiazepines

Opioids are not thought generally to have neuroprotective properties but they do blunt stress-induced responses. Ketamine is an NMDA antagonist and has been shown to be protective in animal models of ischaemia.51 While the benzodiazepines decrease cerebral blood flow and cerebral metabolic rate, these effects are less impressive than with the intravenous anaesthetic agents. Despite occasional reports of neuroprotective benefit,52 these drugs are not generally thought to be useful neuroprotective agents.

Nursing interventions

The nutritional needs of each individual vary according to their age, sex, activity and the severity of any illness. Patients who have been assessed as having a reduced nutritional status, or who fall into a high-risk category, should have their nutritional intake very carefully monitored. All patients require sufficient nutrients to support their basal metabolic rate, level of activity and metabolic response to trauma. Patients with heavily exuding wounds, such as fistulae or leg ulcers, may lose large amounts of protein without it being realised.

Traumatic Brain Injury

Positron emission tomography has revealed focal and diffuse cortical hypometabolism in areas remote from, but transsynaptically connected to subcortical regions affected by DAI. Hyperglycolysis accompanies severe TBI in the first days,85 followed by a reduction in global glucose metabolism. Metabolic rates improve by 1 month after injury regardless of initial severity of injury, but functional outcomes do not necessarily improve, at least in a group of patients that did not have serial PET studies.86 Thus, PET scans of glucose metabolism may be rather unrevealing within a month of TBI, perhaps because of a ceiling effect of the measure in relation to severity of behavioral impairments.

Persistent Vegetative State

Arousal without awareness may follow TBI, hypoxia, carbon monoxide poisoning, and other global cerebral insults (see Chapter 11). After closed-head injury, recovery from a vegetative state is less likely in patients who suffer injuries to the corpus callosum and dorsolateral brain stem.91 F-fluorodeoxyglucose-PET studies point to altered connectivity of association cortices and hypometabolism in prefrontal, pre-motor, parietotemporal, and posterior cingu-late regions.92 Global metabolic rates are often 30 -50 of normal, but islands of relatively normal glucose metabolism associated with fragments of behavior have been identified.92a

Controlling body temperature

Pyrexia may be indicative of infection (see Maintaining a safe environment, Section 2.2.1). Closs (1985) found a 100 association between perioperative pyrexia and the later development of respiratory infection. However, this finding was not supported in a later study by Payman et al. (1989). Pyrexia is a debilitating condition which increases the metabolic rate and is often accompanied by anorexia and dehydration. It may also cause restlessness.

Fetal Development Studies

The first category of research deals with investigations of fetal development and physiology. The purpose of this research is to expand scientific knowledge about normal fetal development in order to provide a basis for identifying and understanding abnormal processes and, ultimately, curing birth deformities, or treating them in utero. These studies primarily involve autopsies of dead fetuses. However, studies of fetal physiology include the fetus in utero as well as organs and tissues removed from the dead fetus. In some instances, this research requires administration of a substance to the woman prior to abortion or delivery by caesarean section. This is followed by analysis to detect the presence of this substance or its metabolic effects in a sample of umbilical cord blood or in the fetal tissue. This research also advances knowledge of fetal development in utero by monitoring fetal breathing movements. Fetal hearing, vision, and taste capabilities have been documented by...

Neuropharmacologic Modulation

The ability to screen drugs for potential positive and negative effects on the rehabilitation of individual patients could have a profound impact on patient management. A few studies have shown that available medications can influence functional networks. Responses to a drug may be state dependent. For example, flenfluramine, which releases serotonin, increased the regional metabolic rate in anterior cingulate and lateral prefrontal cortex in a PET-FDG study of normal young subjects.190 This response is blunted in people diagnosed with an aggressive, impulsive personality dis-order.191 Thus, after TBI, patients with a similar phenotypic behavior may respond to a sero-tonergic agent in different ways, depending on lesion location. Actions of neurotransmitters and modulators (see Chapter 1) can be studied by functional neuroimaging and cortical stimulation techniques.

Looking at the Drug Users Brain

Because of the long-lasting changes in receptors (and presumably many other proteins), the brains of addicts will function differently for a long time.2 In fact, imaging studies clearly show long-lasting changes in brain function in addition to changes in protein levels. Figure 7-3 shows that taking cocaine for a long time causes significant changes in energy metabolism (a measure of function) in the brain. Levels of energy metabolism (indicated by light areas in the image) are compared in a normal subject, a cocaine user who has not taken cocaine for 10 days, and one who has not taken cocaine for 100 days. It is clear that even after 100 days of abstinence, the brain has not returned to normal. Figure 7-3 Energy metabolism is changed in abstinent cocaine abusers for months. The more lightly colored areas are regions of higher energy metabolism. The changes are notable in the frontal lobes, the brain regions where impulses are regulated. These experiments were carried out using PET...

The protectioncomfort contradiction

Protective clothing protects the body from external influence like heat, chemicals, mechanical hazards, foul weather, etc. To achieve this goal, the clothing has to shield the human body from the environment. From a physiological point of view, the human body feels comfortable at about 29 0C in an unclothed state (Wenzel and Piekarski 1982) and at about 26 0C with a clothing insulation of 0.6 clo (1 clo 0.155 m K W) (Olesen and Fanger 1973). However, protective clothing usually has a higher insulation. The bulkiness and the weight of the clothing lead to higher metabolic heat production. The British Standard (BS 7963 2000) provides estimations for the increase in metabolic rate due to the wearing of different types of protective clothing. This increase can be as high as 155 W m2 when wearing highly insulating firefighters' personal protective equipment (including helmet, clothing, gloves and boots). Furthermore, many items of protective clothing have to be watertight, and the ensuing...

Etiology and Epidemiology

The epidemiology of beriberi follows from the role of thiamine in energy metabolism and its deficiency in restricted diets. The population at highest risk for beriberi have been (1) people engaged in heavy labor, such as farmers plowing their fields and soldiers and construction workers (2) pregnant women and subsequently, (3) their nursing infants. The populations in which beriberi has been most prevalent have been of two kinds people confined to institutions, such as prisons, asylums, and naval ships, who are limited to monotonous and restricted diets such as bread and water or fish and rice and people who derive a large portion of their calories from rice from which milling has removed most of the bran in which the thiamine is found. A new population at risk has recently been recognized. In urbanized and industrial countries, beriberi occurs most frequently among alcoholics. At the same time that chronic alcohol consumption impairs the absorption of thiamine by the intestine and...

PaC2 25 mm I IkPuC02 30 mmHR

Jugular bulb oximetry has evolved from a combination of old and new technology. The first measurements taken from the jugular bulb were used to calculate cerebral blood flow (CBF) using the Fick principle.13 Cerebral metabolic rate for oxygen (CMRO2) can be calculated from the CBF and the difference between the arteriovenous oxygen content difference (AVDO2) using the equation As the haemoglobin concentration is the same in arterial and venous blood and the amount of dissolved oxygen is minimal, cerebral metabolic rate for oxygen can be estimated from CBF and the difference in the arteriojugular bulb oxygen saturation.

Obsessivecompulsive disorder OCD

The mechanism by which OCD develops following TBI has been a matter of considerable speculation in the literature. Baxter and colleagues (1992) have found significant correlations between the activity of the orbital prefrontal cortex with that of both the caudate nucleus and the thalamus in those individuals who received treatment for their OCD, but not following treatment in those who responded. They also found that changes in metabolic rate as measured by cerebral blood flow in the head of the caudate on the right directly correlated with successful treatment. Rauch, Jen-ike, Alpert, and colleagues (1994) found an increase in relative cerebral blood flow during an OCD symptomatic state in the right caudate nucleus when compared with the resting state. These patients also featured activation of the left anterior cingulate cortex and the bilateral orbital frontal cortex.

The Modulatory Effect Of Combined Epidural And General Anesthesia

Figure 23-5 Influence of duration of neural blockade on the stress response to surgery. (From Kehlet H Endocrine-metabolic effects. In Raj PP ed Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 193.) Figure 23-5 Influence of duration of neural blockade on the stress response to surgery. (From Kehlet H Endocrine-metabolic effects. In Raj PP ed Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 193.) total afferent barrage after a surgical stimulus. Although most of the studies investigating the effect of regional anesthesia on the surgical stress response have not at the same time looked at the degree of pain relief, there are studies that have simultaneously assessed pain and measured stress responses, which have demonstrated that relief of postoperative pain may not necessarily be followed by a reduction in metabolic demands.12 Thus, even combined analgesic techniques using epidural bupivacaine and morphine to achieve...

Neurological Applications in Diagnosis and Treatment

Characteristic patterns of decreased regional glucose metabolism within the parietal and temporal lobes have been described in patients with AD.y In these patients there is a relative preservation of the calcarine fissure region, sensory motor region, cerebellum, and the basal ganglion region. Decreased metabolic rates for oxygen have also been reported in the same regions that demonstrate areas of decreased glucose metabolism in patients with Alzheimer's disease. Patients with progressive Parkinson's disease have a similar pattern, as seen in patients with Alzheimer's disease. Multiple-infarct dementia occurs after multiple lacunar infarctions. PET generally demonstrates multifocal regions of decreased glucose metabolism y that typically correlate to focal lesions demonstrated on CT scans and MR images. A significant decrease in glucose metabolism within the frontal and temporal lobes has been described in patients with Pick's disease. y Patients with...

In Addition To Medication What Psychiatric Interventions Can Be Helpful For Epilepsy Patients

Appropriate psychiatric interventions depend on a thorough diagnostic evaluation of the patient. As stressed earlier, psychiatric and behavioral problems in epilepsy may result from a variety of factors, which need to be identified before appropriate treatment can be given. Symptoms may be the result of an underlying medical condition that is causing both seizures and psychiatric disturbance toxic-metabolic effects of medications or other substances personal, social, or familial factors related or unrelated to the epilepsy or the location of the seizure focus and the effect of the seizure activity, which may be producing the peri-ictal and interictal disturbances already reviewed. Identifying which factors may be operational in a patient with epilepsy is critical.

Natural and synthetic fibres

Moisture absorbed in garments, in addition to causing discomfort at some stage, adds to the weight carried by the person. In addition it gradually reduces thermal insulation of that particular layer. When activity drops and sweating ceases, the drying of wet clothing layers may deprive the body of more heat than is generated by metabolic rate. The result is a post-chilling effect that may

Assessment of physical activity

Typically an increase in weight of 10 kg occurs over a period of perhaps 2 years. This indicates that the individual has a positive energy balance of some 3040 kcal day, or the equivalent of 1-2 of total energy expenditure. This corresponds to an extra energy intake of less than half a sandwich per day or, on the output side, a walk of 15-30 min day. In the short term these are such small changes in energy balance that they could perhaps correspond to differences in minor unconscious movements ('fidgeting') 4 . No method exists that can measure such differences over a sufficient period of time. The available methods, such as measurements of V02 , step registration, Holter monitoring or activity history, are not very helpful at this low level of long-term change in energy balance. The problem is equally difficult for both energy intake and energy output, and such technical problems make obesity research very complicated. Free living energy expenditure can be measured with reasonable...

BN Finck JJ Lehman PM Barger and DP Kelly

This review covers three topics related to the control of cardiac mitochondrial function in the normal and diseased heart. First, current knowledge of a gene regulatory program involved in the developmental maturation of the cardiac mitochondrial FAO pathway is reviewed. The control of the cardiac mitochondrial FAO by the nuclear receptor peroxisome proliferator-activated receptor a (PPARa) and the retinoid X receptor (RXR) will serve as the starting point, followed by a description of recently discovered links to the program of mitochondrial biogenesis. Second, mechanisms leading to derangements in the PPARa-mediated control of cardiac energy metabolism in the hypertrophied, hypoxic, and failing heart are summarized. Third, the molecular regulatory events responsible for altered energy metabolism in the diabetic heart are reviewed, and a mouse model of diabetic cardiomyopathy is described.

Deactivation of the PPARaPGC1a Complex during Pathologic Cardiac Hypertrophic Growth

Do PPARa-mediated Alterations in Cardiac Energy Metabolism Influence the Cardiac Hypertrophic Phenotype ENERGY METABOLISM IN THE DIABETIC HEART THE ROLE OF PATHOLOGIC ACTIVATION OF THE PPARa PGC-1a REGULATORY PATHWAY Diabetes mellitus is associated with increased cardiac morbidity and mortality (Kannel et al. 1974). Cardiomyopathy commonly occurs in diabetics independent of known risk factors such as coronary disease or hypertension (Rubler et al. 1972). Although little is known about the pathogenesis of diabetic cardiomyopathy, evidence is emerging that functional abnormalities are directly related to derangements in myocardial energy metabolism (Rodrigues et al. 1995 Stanley et al. 1997). In diabetes, the capacity of the heart to switch between utilization of fatty acids and glucose is severely constrained because the uptake and utilization of glucose is dependent on an intact insulin signaling pathway (Fig. 1). Accordingly, in the uncontrolled diabetic state, the heart relies...

Attention Deficit Hyperactivity Disorder

Positron emission tomography studies have reported reduced metabolic rates in, among other regions, the left anterior frontal area, where metabolism correlated inversely with measures of symptom severity (Zametkin et al., 1993). Functional MRI studies have reported abnormal activation of the striatum (Vaidya et al., 1998 Rubia et al., 1999), prefrontal cortex (Rubia et al., 1999), and anterior cingulate cortex (Bush et al., 1999). SPECT studies of ADHD adults have reported marked elevations of dopamine transporter levels in the basal ganglia (Dougherty et al., 1999 Krause et al., 2000), which, after a month of daily methylphenidate treatment, decreased to control levels (Krause et al., 2000). Additional findings in ADHD imaging studies include a smaller cerebellum (Castellanos and Tonnock, 2002), a region thought to be important in attentional processing (Middleton and Strick, 1994).

While theres no such thing as a perfect might for any one individual a certain range of calories is needed to maintain

Your setpoint weight is determined by genetic factors which are not changeable, and by your metabolic rate, which is explained in 4 below. Any daily food intake below 1200 calories for two weeks or more lowers the setpoint, as does keeping your weight less than your setpoint range. When this happens, all chemical reactions in your body slow down your muscle tone, body temperature, and blood sugar levels decrease and the ability of your heart muscle to work declines to 50 of its previous rate per minute. The longer you diet restrict, the longer it will take for your body to normalize and its setpoint to return to normal. 4. What is metabolism (metabolic rate) Metabolism is the rate at which your body burns calories. Partial or total starvation is a physiological stress, which the body reacts to by automatically slowing down its metabolic rate. Metabolism fluctuates on a regular, 24-hour cycle it tends to be slowest upon awakening in the morning and gradually increases to a peak around...

Predictors of Functional Gains

Metabolic and functional activation studies may reveal information relevant to functional recovery (see Chapter 3). For example, a higher global and contralateral cerebral metabolic rate for glucose within 1 to 2 weeks of an acute stroke correlated with a better functional outcome in survivors at a mean of 3 and 50 months.201 Low glucose consumption within the unaffected hemisphere in hypertensive patients was associated with poorer ADLs, perhaps because of a subclinical hypertensive ar-teriopathy producing tissue damage that limited compensation. Perilesion metabolic activation and activations associated with greater motor recovery tend to correlate with functional gains, but too few serial studies have been completed to establish meaningful predictors. Activations that change over the course of training, especially for a motor task or a working memory task, may come to serve as physiologic markers of the capacity for improvement in ADLs and the effectiveness of rehabilitative...

Role of PAdrenergic Receptor Subtypes in Regulating Cardiac Function

In the Cardiovascular and Metabolic Response to Exercise Maximal exercise is associated with near maximal sympathetic nervous system activity and dramatic changes in heart rate, contractility, and vascular tone. Surprisingly, even though P1-ARs are essential for catecholamine stimulation of chronotropy and inotropy, P1-AR-KO mice exhibited the same exercise capacity as wild-type controls (32,36). The heart rate response to exercise in P1-AR-KO mice was markedly reduced compared to wild-type mice yet, there were no differences between P1-AR-KO mice and wild-type mice in VO2 and VCO2 over the entire range of workloads, suggesting no difference in metabolic response to exercise and no difference in O2 extraction. Thus, P1-AR-KO mice must compensate for their slower heart rates with greater increases in stroke volume, presumably through preload-dependent mechanisms (36). Using the same graded treadmill protocol, P2-AR-KO mice exercised for a longer duration than did wild-type mice (29)....

Immediate postoperative care

The provision of a comfortable bed in a warm, but not too hot, environment is beneficial. Food and water should be offered as early as possible in the postoperative period. Pain and inflammation increase the basic metabolic rate and a high level of nutrition is required to promote healing. Offering food as early as possible not only speeds recovery but can also have a soothing effect.

Clinical Manifestations

free radicals energy metabolism Figure VIII. 102.1. Scheme illustrating the mechanism of MPTP toxicity at nigral dopamine neurons in primates. MPTP, which is lipophilic, enters the brain where it is transformed into MPP+ by monoamine oxidase B located in glial cells or in serotonergic neurons. MPP+ is taken up into the dopaminergic (DA) neurons, where it accumulates, by dopamine reuptake mechanisms. The binding of MPP+ to neuromelanin might assist in the accumulation of MPP+, or might contribute to its toxicity. MPP+ within the neurons is assumed not to undergo redox cycling to reproduce free radical species but, rather, to be actively accumulated by mitochondria, where it inerferes with mitochondrial energy metabolism, leading to cell death. The precise mechanism of MPP+ toxicity remains unknown. The sequence of events leading to MPTP toxicity can, in theory, be inhibited at a number of points (1) Selective monoamine oxidase B inhibitors (MAOI B) such as deprenyl inhibit the...

Fibreyarn coated applications

A metallised coating onto the surface of the fibre or yarn, or within a bi component yarn (Fig. 13.2) has an antimicrobial effect. Complexing compounds, based on metals such as silver, copper or mercury cause inhibition of the active enzyme in the pathogen, effecting the bacteria's metabolic rate, thus rendering it unable to replicate or function.

Setting Realistic Goals

Following a healthy food plan is only half of the weight-loss equation You've gotta move to lose Numerous studies have shown that exercise helps promote weight loss and weight maintenance by revving up your metabolism (that is, burning more calories). What's more, exercise relieves stress and can even psych up your state of mind so that you're motivated to make smart food choices during the day.

Treatment of Hypothyroidism

Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic LT4 is the treatment of choice for almost all patients with hypothyroidism.11 12 Using LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. Peripheral tissues convert T4 to T3 as needed, based on metabolic demands. If T3 is used to treat hy-pothyroidism, the peripheral tissues lose their ability to control local metabolic rates. LT4 also has distinct pharmacokinetic advantages over T3. With a 7 to 10 day half-life, LT4 provides a very smooth dose-response curve with little peak and trough effect. In a small number of patients who have impairment of conversion of T4 to T3, addition of T3 may be warranted. T3, with a 24-hour half-life, provides a significant peak and trough effect, and many patients will have symptoms of thyrotoxicosis after each dose is administered. For patients who have difficulty adhering to...

Glucose Metabolism Disorders Hypoglycemia

Unlike other body tissues, the CNS relies almost exclusively on glucose as an energy substrate. CNS features that promote its vulnerability to hypoglycemia include its low glucose level (about 25 percent of the serum glucose value), its inability to store significant glucose as glycogen, and the high cerebral metabolic rate (5 mg 100 g brain tissue min) for glucose. yj Thus, for a 1400 g brain, the glucose requirement is 70 mg min. The brain's dependence on glucose, coupled with its limited glycogen stores, results in rapid CNS dysfunction when hypoglycemia occurs and permanent neurological

Identification of Sperm Oxidative Stress from Clinical History

Male Infertility Causes Mnemonics

Cancer and its treatment by chemotherapy and radiation are known to be a potent systemic oxidative insult, potentially impairing sperm function. Drugs such as the chemotherapy agent cyclophosphamide have been linked with sperm oxidative stress. Administration of cyclophosphamide to animals is reported to increase testicular malondialdehyde (MDA) levels and produce a fall in testicular catalase, implying the presence of oxidative stress 86, 87 . Similarly, radiation exposure has been shown to cause a systemic inflammatory reaction and increase in oxidative stress in both the irradiated tissue and non-irradiated bystander normal tissue 88, 89 . DNA fragments of apoptotic irradiated cancer cells are released into the intercellular space and interact with the DNA-binding receptors of the bystander non-irradiated cells, initiating activation of lymphocyte signalling pathways associated with synthesis of reactive oxygen and nitrogen species, thereby inducing secondary oxidative stress 90 ....

Molecular mechanisms of injury progression Figure

In the border zone of permanent focal ischemia or in the ischemic territory after transient vascular occlusion, cellular disturbances may evolve that cannot be explained by a lasting impairment of blood flow or energy metabolism. These disturbances are referred to as molecular injury, where the term molecular does not anticipate any particular injury pathway (Figure 1.8). The molecular injury cascades (Figure 1.8) are interconnected in complex ways, which makes it difficult to predict their relative

Bio Electrical Impedance

First find your BMR (basal metabolic rate the amount of calories needed to perform your normal bodily functions at rest). Plug your own stats into the formula, and figure out what it will take calorically to melt away those unwanted pounds. Understand that no one should ever eat less than 1,200 calories per day you will slow down your metabolism and set yourself up to gain all the weight back. Even if you are very petite, and the math works out to be less than 1,200 stick with 1,200 calories and jack up your exercise.

The Fetalto Adult Energy Metabolic Switch Postnatal Induction of Cellular Mitochondrial Energy Transduction Production

Cordio Vascuiar System Indction

The postnatal induction of MCAD and M-CPT I gene expression in the developing heart provided proof of concept that these genes were targets for upstream regulatory pathways involved in the transcriptional control of my-ocardial energy metabolism. The initial approach involved mapping the cis-acting regulatory elements within the promoter regions of these genes. Two complementary experimental strategies were employed. First, gene promoter regulatory regions involved in the cardiac developmental control of MCAD gene expression were mapped in vivo in promoter-reporter transgenic mice (Disch et al. 1996). Second, relevant M-CPT I and MCAD gene promoter elements were defined in rat neonatal cardiac my-ocytes in culture (Disch et al. 1996 Brandt et al. 1998). The latter approach revealed that fatty acid substrate activated the transcription of the FAO enzyme genes. Both strategies demonstrated that DNA sequences containing recognition sites for members of the nuclear hormone receptor...

Forearm Exercise Testing

Muscle fibers develop tension and shorten, thereby producing movement. These processes, including contraction and relaxation, are coordinated by the nervous system and are energy-requiring. Skeletal muscle meets its energy demands by converting chemical energy into mechanical energy. One feature unique to skeletal muscle, compared with other tissues, is the energy requirement difference between its resting and fully active states, a value that can approach two to three orders of magnitude.' When the metabolic energy demands of active muscle cannot be met by the available energy sources, muscle fatigue and dysfunction occur. In such settings, when abnormalities of muscle biochemistry are responsible for the decreased energy supply, the term metabolic myopathies is applied. For diagnostic purposes, these disorders can be divided into two groups (1) exercise-induced (dynamic) myopathies, in which symptoms such as weakness, cramping, myalgias, and stiffness appear during exercise and (2)...

Electroconvulsive Therapy

(high-voltage spikes and waves), and coherence in ictal-EEG between right and left hemisphere are all important factors in ECT's efficacy (Fink et al., 1982 McCall et al., 1995). So are the stimulated compensatory mechanisms for stopping the seizure. A greater suppression of the postictal EEG has been shown to be a key factor. Fink and colleagues demonstrated a relationship between frontal delta activity and response to treatment (Fink, 1984a). Neuroimaging studies have also shed light on this dynamic interplay (Rosenberg et al., 1988 Nobler et al., 1999). Studies have shown an increase in cerebral blood flow (CBF) up to 300 percent of baseline values and in cerebral metabolic rate (CMR) up to 200 percent during the ictal period. In contrast, these measures decrease postictally (Nobler et al., 2001). In imaging studies, it has been found that the degree of prefrontal deactivation following ECT correlated with improvement. Even when imaged 2 months following ECT, the inverse...

Stimulants amphetamine ephedrine cocaine and caffeine

Substances belonging to this group range from the potent amphetamines to the weaker caffeine and ephedrine. The substances are called sympath-omimetics and imitate the effects of the stress hormones epinephrine and norepinephrine. Amphetamines were synthesized first in 1887 and were initially commercially available as a nasal decongestant. They cause the release of excitatory neurotransmitters, such as dopamine, to stimulate the central nervous system (CNS). The main effects on the CNS include wakeful-ness, alertness and a decreased sense of fatigue, mood elevation, increased self-confidence and a decreased appetite. The physical effects include increased heart rate, redirection of blood flow from the gastrointestinal tract to the muscles, and an increased fat metabolism. Amphetamine carries a high potential of tolerance, i.e. dosage has to be increased after prolonged use to induce the same effect. Although several CNS-acting stimulants are suspected to be performance enhancing,...

Intraoperative Management Of Neurosurgical Patients

The anaesthetist needs to aim for a smooth induction of anaesthesia, avoiding coughing, straining or the production of undue hypo- or hypertension. In the adult an intravenous induction of anaesthesia is normal either thiopentone or propofol may be used and will produce a fall in ICP by lowering the cerebral metabolic rate (CMRO2) and the CBF.45 Propofol has been demonstrated to produce a 32 fall in cerebrospinal fluid (CSF) pressure 2 min after the induction of anaesthesia with 1.5 mg kg. The fall in CBF and ICP may be quite short with propofol, the CSF pressure returned to normal values within 3 min. 4. Michenfelder JD. The interdependency of cerebral function and metabolic effects following maximum doses of thiopental in the dog. Anesthesiology 1974 41 231. 17. Harp JR, Wollman H. Cerebral metabolic effects of hyperventilation and deliberate hypotension. Br J Anaesth 1973 45 256. 10. Scheller MS, Teteishi A, Drummond JC, Zornow MH. The effects of sevoflurane on cerebral blood flow,...

Various Transporter Defects Hartnups Disease

Transporter (GLUT1) in brain microvessels at the blood- brain barrier, causing low CSF glucose (hypoglycorrhachia) and therefore decreased cerebral energy metabolism and brain function. GLUT1 is coded by a gene localized to chromosome 1 and is developmentally regulated, with the messenger RNA in brain increasing with increasing cerebral metabolic rate for glucose in infancy and childhood. Symptoms occur when this rate increases in early infancy, doubling or tripling that in the neonatal and fetal periods. This is a very rare condition, probably a spontaneous mutation, with patients being symptomatic heterozygotes. At about age 3 months, a perfectly normal infant develops seizures--myoclonic, atypical absences, or unclassifiable--that are refractory to antiepileptic drugs. Developmental delay occurs the longer seizures are uncontrolled and the diagnosis is undiscovered, which can culminate in mental retardation and secondary microcephaly. The differential diagnosis includes any disease...

The principle of functional and activation studies using positron emission tomography PET

The energy demand of the brain is very high and relies almost entirely on the oxidative metabolism of glucose (see Chapter 1). Mapping of neuronal activity in the brain can be primarily achieved by quantitation of the regional cerebral metabolic rate for glucose (rCMRGlc), as introduced for autoradiographic experimental studies by Sokoloff et al. 7 and adapted for positron emission tomography (PET) in humans by Reivich et al. 8 . The cerebral metabolic rate for glucose (CMRGlc) can be quantified with PET using 2- 18F fluoro-2-deoxyglucose (FDG) and a modification of the three-compartment model equation developed for autoradiography by Sokoloff et al. 7 . Like glucose, FDG is transported across the blood-brain barrier and into brain cells, where it is phosphorylated by hexokinase. However, FDG-6-phosphate cannot be metabolized to its respective fructose-6-phosphate analog, and does not diffuse out of the cells in significant amounts. The distribution of the radioactivity accumulated in...

Physiology of Sporulation of Clostridia

Clostridium Sporulation Pathway

Exposure of Clostridia to conditions of nutrition depletion activates alternate metabolic pathways. Sporulation is the ultimate example of this adaptation response, which begins at the onset of stationary phase. Unlike most adaptive responses, bacterial sporulation involves several metabolic pathways associated with morphological, physiological and biochemical changes and can affect end products associated with energy metabolism. Several changes involve metabolites associated with stationary phase and sporulation. However, not all are sporulation-related or specific. Studies of the sporulation process at the molecular level have just begun in the genus Clostridium but are extensive in the case of aerobic sporeformers, Bacillus subtilis in particular.1'2 This chapter presents some aspects of the current knowledge about how sporulation affects the metabolism of the Clostridia and focuses on the methods that promote in vitro sporulation and the regulation of sporulation-associated...

Efferent Autonomic Pathways

Alpha-adrenergic receptors mediate sympathetically induced pupillary dilatation (mydriasis), vasoconstriction, and contraction of the vas deferens and bladder and rectal internal sphincters. Beta receptors mediate cardiac stimulation, vasodilation, bronchodilatation, relaxation of the bladder, and endocrine-metabolic effects. Muscarinic receptors mediate pupil constriction (miosis), salivary and lacrimal secretion, cardiac inhibition, bronchoconstriction, stimulation of motility and secretion in the gastrointestinal tract, evacuation of the bladder and rectum, and erection.

Temperature Regulation And Maintenance

The metabolic rate at this temperature is minimal. The temperature of such an environment is 34 C for the premature neonate, 32 C for the neonate at term and 28 C for the adult. If neonates are allowed to become hypothermic during anaesthesia, unlike adults they attempt to correct this by non-shivering thermogenesis. Metabolic rate increases and oxygen consumption may double. The increase in metabolic rate puts an additional burden on the cardiorespiratory system and this may be critical in neonates with limited reserve. The release of norepinephrine in response to hypothermia causes vasoconstriction, which in turn causes a lactic acidosis. The acidosis in turn favours an increase in right-to-left shunt, which causes hypoxaemia. As a result, a vicious positive feedback loop of hypoxaemia and acidosis is set up. The protective airway reflexes of a hypothermic neonate are obtunded, thereby increasing the risks of regurgitation and aspiration of gastric contents. The action of most...

Factors affecting drug metabolism

Metabolic systems A key metabolic system found in the liver is known as the mixed function oxidase system. The enzyme involved, cytochrome P450, is induced by the presence of one or more of the drugs it metabolizes. This means that consistent exposure to drugs metabolized by P450 will increase the rate of metabolism and result in ever-increasing doses being required to have a therapeutic effect. An example of this is the drug phenobarbital, used for controlling epileptic seizures. Other drugs affected by P450 would also be metabolized more quickly, so the dose rate of these would also have to be increased.

Energy requirements of brain tissue

The energy demand of the nervous tissue is very high and therefore sufficient blood supply to the brain must be maintained consistently. A normal adult male's brain containing approx. 130 billion neurons (21.5 billion in the neocortex) 49 comprises only 2 of total body mass, yet consumes at rest approximately 20 of the body's total basal oxygen consumption supplied by 16 of the cardiac blood output. The brain's oxygen consumption is almost entirely for the oxidative metabolism of glucose, which in normal physiological conditions is the almost exclusive substrate for the brain's energy metabolism 50 (Table 1.1). It must be kept in mind that the glucose metabolized in neuronal cell bodies is mainly to support cellular vegetative and house-keeping functions, e.g. axonal transport, biosynthesis of nucleic acids, proteins, lipids, as well as other energy-consuming processes not related directly to action potentials. Therefore the rate of glucose consumption of neuronal cell bodies is...

Physiology anatomy and biochemistry of the adrenal gland

Adrenal Glands Anatomy

The zona fasciculata produces the glucocorticoid hormone cortisol. Cortisol is responsible for maintaining homeostasis of carbohydrate, protein, and fat metabolism. Its secretion follows a circadian rhythm, generally beginning to rise at approximately 4 am and peaking around 6 to 8 am. Thereafter, cortisol levels decrease throughout the day, approach 50 of the peak value by 4 pm, and reach their nadir around midnight. The normal rate of cortisol production is approximately 8 to 15 mg day. Cortisol plays a key role in the body's response to stress. Its production increases markedly during physiologic stress such as during acute illness, surgery, or trauma. In addition, certain conditions such as alcoholism, depression, anxiety disorder, obsessive-compulsive disorder, poorly controlled diabetes, morbid obesity, starvation, anorexia nervosa, and chronic renal failure are associated with increased cortisol levels. High total cortisol levels are also observed in the presence of increased...

Acclimatization to cold

Practically no studies exist in which the effects of cold acclimatization on physical performance have been studied. We know from some studies that the unpleasantness of cold sensations becomes reduced or habituated after 1-4 daily cold exposures, and that increased sympathetic activity and shivering is attenuated within a week 12-14 . True cold acclimatization is difficult to induce in humans. Three types of adaptation to cold are described (i) metabolic, where a greater metabolic response to cold stress is developed 15,16 (ii) hypothermic, where core temperature falls (e.g 12 ) and (iii) insulative 17 with a lowering of the skin to environment gradient and heat loss, and with little change in core temperature and metabolic rate during cold exposure. Immersion in cold water 5 days per week over 5 weeks has been found to induce the type of adaptation described as insulative 18 a lowering of resting rectal temperature, a slower rise in metabolic rate (indicating a delay in onset of...

How is a PET scan performed

FDG is currently the most commonly used radiotracer. It is transported and becomes trapped intracellular as a result of phosphorylation by hexokinase. FDG accumulates at sites of neoplasia and inflammation as cells in these regions have an increased metabolic rate. Because FDG competes with nonradioactive glucose, recent eating or diabetes with an elevated blood sugar greater than 150 mL dL will decrease scan sensitivity. 18-F-NaF is a bone-specific tracer that has application in PET imaging of the musculoskeletal system (Fig. 13-6).

Biologic Basis for Hand and Upper Extremity Splinting

Because wounds remain metabolically reactive for long periods of time, surgery or a second injury may further increase scar collagen synthesis and lead to more scarring. It may be many months before a wound is sufficiently healed to allow one to proceed with further reconstructive surgical procedures. The physical characteristics of the injured tissues may provide important clues as to the metabolic state of the wound. This prolonged period of metabolic activity

Central Nervous System Monitoring

Conscious state monitoring is necessary to detect the impact of drugs, metabolic response, and or cardiovascular and respiratory changes. Propofol is frequently used to sedate patients, but methohexital, barbiturates, and other drugs, especially benzodiazepines, are also used. Sometimes fentanyl or remifentanil in variable doses is administered as a rescue analgesic during the operation, because often it is not possible to continue with regional anesthesia. Thus, the regional anesthetic technique is changed to other complex techniques that must also be monitored. An EEG reading is necessary when there is a risk of cerebral hypoxemia, or when the effect of drugs on cerebral function must be evaluated, especially drugs that are capable of depressing the cerebral function. In many neurosurgical centers, use of EEG with carotid endarterectomy is a good example, because during this type of surgery, the patient is kept awake under regional anesthesia (superficial cervical block plus local...

Physiological Determinants of RCBF and RCBV

Increases in local neuronal activity are accompanied by increases in regional cerebral metabolic rate (rCMR). Until recently, the increases in rCBF and oxygen consumption produced during such functional activation were thought to be closely coupled to the cerebral metabolic rate of utilization of O2 (CMRO2) and glucose (CMRglu). However, it has now been clearly shown that increases in rCBF during functional activation tend to track glucose utilization but may be far in excess of the increase in oxygen consumption.19 This results in regional anaerobic glucose utilization and a consequent local decrease in oxygen extraction ratio and increase in local haemoglobin saturation. The resulting local decrease in deoxyhaemoglobin levels is used by functional MRI techniques to image the changes in rCBF produced by functional activation. Despite this revision of the proportionality between increased rCBF and CMRO2 during functional activation in the brain, the relationship between rCBF and...

Morphology and Anatomic Distribution

Astrocyte Morphology

Like processes, which are insinuated between and around the various components of the nervous tissue (12). Microinjection of single hippocampal astrocytes with fluorescent dyes demonstrates that each astrocyte occupies a discrete area that is free of processes from any adjacent astrocytes thus defining its own anatomical domain (Fig. 1b). Only the most peripheral processes interdigi-tate with one another in a narrow interface within which < 5 of the volumes of adjacent astrocytes overlap (13, 14). Glial fibrillary acidic protein (GFAP) labels only the major processes of astrocytes, many of the smaller processes being nonreactive with GFAP. These smaller processes fill a volume that is best defined as a polyhedron (12-14). These fine processes have a significantly higher density of mitochondria as compared with the surrounding neuronal processes, synapses, other glial processes, and endothelial cells, supporting the concept that oxidative metabolism is a major part of the energy...

The Bodys Response to Stress

Figure 9-1 The body's stress response. When someone is stressed, the brain's stress pathways are activated such that the hypothalamus, found in the base of the brain, sends a chemical signal, CRH, to the pituitary gland, which sends another chemical signal, ACTH, to the adrenal glands (found near the kidneys). The adrenals secrete cortisol, which is the well known stress hormone into the blood. Cortisol then stimulates a metabolic response and circulates back to the brain to stop or regulate the release of chemicals from the hypothalamus and pituitary. This regulation is important so that this stress response is not a runaway process. Many addicts are hypersensitive to stress. (From and Roberto Osti, with permission.) Figure 9-1 The body's stress response. When someone is stressed, the brain's stress pathways are activated such that the hypothalamus, found in the base of the brain, sends a chemical signal, CRH, to the pituitary gland, which sends another chemical signal, ACTH, to the...

Creativity Meditation and Hypnosis

There are psychophysiological markers for hypnagogia, hypno-pompia, and napping. In the case of meditation, a number of studies have identified markers such as reduced respiration rate and volume of air breathed, reduced oxygen consumption and carbon dioxide elimination, and reduced blood lactate. In these studies, heart rate and the skin's electrical conductance decreased, but the frequency of alpha (and sometimes that of theta) brain waves increased. All of this suggests reduced energy metabolism, autonomic nervous system arousal, cortical energy metabolism, autonomic nervous system arousal, and cortical arousal. Additional research indicated that reduced arousal during meditation is due to its rest and relaxation aspects rather than to the specific meditation practice employed. However, it is probably more accurate to speak of meditative states of consciousness than to hypothesize a single meditative state, because different practices may emphasize rapid breathing and active...

Diagnosis Of Dementia

Structural neuroimaging using noncontrasted CT or MRI is a mainstay of the dementia evaluation. Structural imaging can reveal reversible and arrestable causes of dementia such as space-occupying lesions (hematomas, tumors, hydrocephalus, etc.). In patients with neurodegenerative diseases, structural imaging can sometimes reveal patterns of atrophy and other changes that can help with diagnosis. Functional neu-roimaging using SPECT or positron emission tomography (PET) scanning measures cerebral blood flow and cerebral metabolic rate, respectively, and can reveal patterns of dysfunction characteristic of certain illnesses.

Combining Antiangiogenic Agents with Metronomic Chemotherapy Enhances Efficacy against Latestage Pancreatic Islet

Translation of preclinical results using animal models to clinical trials have typically proved challenging, both in extrapolating experimental design and in interpreting the predictive value of the animal data. In particular, traditional xenograft mouse models for experimental therapeutic trials of anticancer agents have a spotty history in their predictive value. Much has been attributed to the differences in pharmacokinetics consequent to distinctive mouse and human metabolism. Another profound difference, often unmentioned, is that traditional xenotrans-plant models involve cultured tumor cells that are inoculated into different sites, most frequently subcutaneous, where tumor cells assemble into nodules and grow. In contrast, GEM carrying oncogenes or disruptions in tumor suppressors can develop tumors de novo, much like human cancers, originating out of once-normal cells in their natural tissue microenvironments, typically in multistep pathways. These models are providing new...

Deterioration of Nutritional Status and Need for Support

Even previously healthy patients may lose nutritional ground rapidly once they are hospitalized. Surgery and the stress of disease increase caloric requirements. The amount of these increases can be calculated using one of a number of predictive equations for determining resting metabolic rate (RMR) in kilocalories per day (kcal day), which is the largest component of overall calorie expenditure. One frequently used model is the Harris-Benedict equation (1919), as follows For men (See Web Resources for resting metabolic rate basal metabolic rate and resting energy energy basal energy expenditure calculators.) These equations predict the resting metabolic rate, and caloric requirements increase beyond this figure, based on the patient's illness and other metabolic demands. The resting energy expenditure (REE) is 1.2 to 1.3 multiplied by the RMR. This figure is further altered by the level of stress. An example is to multiply REE by 1.1 To determine total daily calorie needs, multiply...

Effects on Acute Phase Response and Cytokines

In a prospective randomized study of laparoscopic versus small-incision open cholecystectomy, Squirrell et al. (20) demonstrated significantly lower C-reactive protein levels following laparoscopic cholecystectomy. However, they found no differences in serum cortisol levels between the two groups and concluded that the neuro-endocrine component of the metabolic response, i.e., cortisol, was not influenced by the type of surgical access (20). These findings were contradicted by McMahon et al. (16), who found no differences in the levels of C-reactive protein or other acute-phase response proteins such as albumin and transferrin between laparoscopic and minilaparotomy cholecystectomy. Because open cholecystectomy in this study was performed through a much smaller incision than would normally be used for open surgical procedures, these results indicate that the trauma of abdominal access influences immunological function. Other studies of laparoscopic versus small-incision...

Physiologic Effects of Corticosteroids

Cortisol exerts its effect by regulating gene transcription after binding to glucocorticoid receptors within the cell.9 Cortisol has a large number of metabolic effects on several tissues. However, many of the effects of glucocorticoids are based on studies of patients, animals, and cells with non-physiologically high or low levels of glucocorticoids.

Intravenous Local Anesthetics

The effect of intravenously administrated local anesthetics on postoperative pain and endocrine metabolic responses is minimal.13 Figure 23-2 Neural blockade techniques that may influence the response to surgical injury. (From Kehlet H Endocrine-metabolic effects. In Raj PP ed Clinical Practice of Regional Anesthesia. New York, Churchill Livingstone, 1991, p 188.)

Translation of experimental concepts to clinical stroke

Positron emission tomography (PET) is still the only method allowing quantitative determination of various physiological variables in the brain and was applied extensively for studies in patients with acute, subacute or chronic stages of ischemic stroke (review in Heiss 61 ). The introduction of scanners with high resolution (2.5 to 5 mm for human, 1 mm for animal application) made PET a tool for studying animal models and to compare repeat examinations of various variables from experiments to the course of disease in humans. The regional decrease of cerebral blood flow (CBF) can be directly observed in PET as in other studies (SPECT, PW-MRI, PCT). However, even in early PET studies 90 preserved glucose consumption was observed in regions with decreased flow in the first hours after the ictus. In the 1980s, PET with oxygen-15 tracers became the gold standard for the evaluation of pathophysiological changes in early ischemic stroke 91 . The quantitative measurement of CBF, CMRO2, OEF...

Progression of ischemic injury

With the advent of non-invasive imaging evidence has been provided that brain infarcts grow. This growth is not due to the progression of ischemia because the activation of collateral blood supply and spontaneous thrombolysis tend to improve blood flow over time. Infarct progression can be differentiated into three phases. During the acute phase tissue injury is the direct consequence of the ischemia-induced energy failure and the resulting terminal depolarization of cell membranes. At flow values below the threshold of energy metabolism this injury is established within a few minutes after the onset of ischemia. During the subsequent subacute phase, the infarct core expands into the peri-infarct penumbra until, after 4-6 hours, core and penumbra merge. The reasons for this expansion are peri-infarct spreading depressions and a multitude of cell biological disturbances, collectively referred to as molecular cell injury. Finally, a delayed phase of injury evolves which may last for...

Periinfarct spreading depression

A functional disturbance contributing to the growth of the infarct core into the penumbra zone is the generation of peri-infarct spreading depressionlike depolarizations. These depolarizations are initiated at the border of the infarct core and spread over the entire ipsilateral hemisphere. During spreading depression the metabolic rate of the tissue markedly increases in response to the greatly enhanced energy demands of the activated ion-exchange pumps. In the healthy brain the associated increase of glucose and oxygen demands is coupled to a parallel increase of blood flow but in the peri-infarct penumbra this flow response is suppressed or even reversed 67 . As a result, a misrelationship arises between the increased metabolic workload and the low oxygen supply, leading to transient episodes of hypoxia and the stepwise increase in lactate during the passage of each depolarization.

Paravertebral Blockade

The majority of data that demonstrate that regional anesthesia with local anesthetics may modify the surgical stress response come from studies in which epidural local anesthetics were used.12 12 These studies also document that most of the classic endocrine metabolic response is mediated by neural stimuli, whereas other responses (i.e., inflammatory responses) are generally mediated by humoral factors.12 12

Metabolic Strategy of Human Spermatozoa 1011 Introduction

In addition to the biochemical changes that experiment during the process of capacitation, sperm are exposed to significant environmental changes as they move from the testis to the distal portion of the oviduct where fertilization normally takes place. Exposure of epididymal sperm to the seminal plasma during ejaculation reinitiates motility and sharply increases sperm energy metabolism. Further environmental changes occur in the female reproductive tract as sperm move out from the seminal plasma into the uterine and oviductal fluids. Under these conditions, sperm survival is going to depend on the efficient utilization and control of metabolic of nutrients present in the extracellular medium of the female reproductive tract.

Impact of Sperm Metabolic Strategy on Sperm Motility

The energy metabolism of a cell type should be related to its function. This relation has been termed as the metabolic strategy of the cell. In the case of sperm, the question that may be asked is is sperm's metabolic strategy geared to the series of reactions related to the process of fertilization including motility, or does the maintenance of motility dominate the metabolic strategy of the spermatozoon These questions can be clarified by a close look at the kinetic properties of pyruvate kinase in sperm, as compared with that of liver and muscle, as well as by looking at the metabolic coupling of pyruvate kinase with flagellar ATPase. Pyruvate kinase has access to its substrates in permeabilized epididymal sperm while remaining bound to the sperm cytoskeleton and suffering minimal perturbation from the pemeabilization procedure 9 , Epididymal sperm are usually immotile but motility is restored by suspending sperm in KCl medium containing Mg2+ upon addition of 3 mM ATP, according to...

Preoperative Fasting

Morbidity and mortality caused by aspiration of gastric contents are extremely rare in children undergoing elective surgery. What is becoming increasingly clear is that prolonged periods of starvation in children, especially the very young infant, are harmful. These children, who have a rapid turnover of fluids and a high metabolic rate are, at risk of developing hypoglycaemia and hypovolaemia. Research has shown that children allowed unrestricted clear fluids up to 2 h before elective surgery have a gastric residual volume equal to or less than that of children who have been fasted overnight. The essential message is that children should, rather than could, be given clear fluids up to 2 h before induction. Solids (including breast and formula milk) should not be given for at least 4 h before the anticipated start of induction. In the emergency setting, e.g. the child who has sustained trauma shortly after ingesting food, it is probably best (if possible) to wait 4 h before inducing...

Normal Maintenance Needs

Regardless of the disease process, water and electrolyte losses occur in urine and as evaporative losses from skin and lungs. It is evident from Figure 39.3 that a normothermic 70 kg patient with a normal metabolic rate may lose 2500 ml of water per day. Allowing for a gain of 400 ml from water of metabolism, this hypothetical patient needs 2000 ml day-1 of water. As a rule of thumb, a volume of 30-35 ml kg-1 day-1 of water is a useful estimate for daily maintenance needs.

Myocardial preservation

Most surgical techniques on the heart require an immobile heart. On bypass, the aorta is cross-clamped between the aortic cannula and the aortic valve, thus isolating the heart from the flow of oxygenated blood. During aortic cross-clamping, ischaemic damage to the myocardium can be minimized by attempts to reduce myocardial oxygen consumption. Currently, techniques of myocardial preservation include hypothermia to reduce basal metabolic rate and cardiac arrest to reduce oxygen requirements to a minimum, the latter usually achieved by injecting 500-1000 ml of

Central nervous system

Anaesthesia is induced within 20-40 s after i.v. administration in otherwise healthy young adults. Transfer from blood to the sites of action in the brain is slower than with thiopental, and there is a delay in disappearance of the eyelash reflex, normally used as a sign of unconsciousness after administration of barbiturate anaesthetic agents. Overdosage of propofol, with exaggerated side-effects, may result if this clinical sign is used loss of verbal contact is a better end-point. EEG frequency decreases, and amplitude increases. Propofol reduces the duration of seizures induced by ECT in humans. However, there have been reports of convulsions following the use of propofol and it is recommended that caution be exercised in administration of propofol to epileptic patients. Normally cerebral metabolic rate, CBF and intracranial pressure are reduced.

Thyroid hormone physiology and biosynthesis

Thyroid hormones are essential for proper fetal growth and development, particularly of the CNS. After delivery, the primary role of thyroid hormone is in the regulation of energy metabolism. These hormones can affect the function of virtually every organ in the body. The parafollicular C cells of the thyroid gland produce calcitonin. The function of calcitonin and its therapeutic use are discussed in other chapters in this book.

Laparoscopic Pyeloplasty In Children

Both transperitoneal and retroperitoneal routes, and lower insufflation pressures (12 mmHg) were employed. Recently robot-assisted pyeloplasty was performed using the da Vinci Surgical Systema with equally good results in a series of 13 children older than 3.5 years (36). However, longer follow-up and further evaluation of the metabolic effects of CO2 insufflation in children undergoing laparoscopic surgery are awaited before establishing laparoscopic pyeloplasty the standard of care in this population.

Adjunctive Metabolic Intervention at the Time of Coronary Revascularization

In a randomized, placebo-controlled, double-blind trial, the effect of 6 months of pioglitazone treatment on neointima volume measured by IVUS was studied in 50 nondiabetic patients undergoing BMS-based PCI.72 Compared with controls, subjects receiving pioglitazone had significant reductions in both neo-intima volume within the stented segment and binary restenosis rate. Importantly, in this study population of nondiabetic patients, pioglitazone treatment did not significantly change fasting blood glucose, fasting insulin, HbA1c levels, or lipid parameters. These data bolster the hypothesis that TZD, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

Nonenzymatic Epididymal Scavengers

The primary role of l-carnitine is in transferring long-chain fatty acids across mito-chondrial membranes, thus facilitating oxidation within mitochondria during energy production. It is found concentrated in tissues, such as muscles, in which energy demand is high. Intriguingly, l-carnitine was shown to be present at very high concentrations in the mammalian epididymis and spermatozoa (in the mM range) far above circulating levels (in the M range). Epididymal intraluminal carnitine concentration increases gradually along the epididymis, reaching its maximum in the cauda compartment 20 . The prevalent view is that carnitine is not synthesized by the epididymis epithelia but rather is transported from the systemic compartment. Although, it is quite conceivable that, as the energy substrate for spermatozoa carnitine might support sperm respiration and motility, it is however difficult to understand why this should be the case in a compartment where spermatozoa are immotile. Therefore,...

Physiologic responses to cold exposure

Technical developments have changed the situations in which humans are exposed to cold. The number of people working outdoors in cold conditions is presently declining, while that of people participating in recreational activities, e.g. winter sports is evidently increasing. Physical fitness is important for the ther-moregulatory responses to cold. Fit people have a higher metabolic response and a higher skin temperature at the onset of shivering. On the other hand, body fat provides protection against cooling 5 .

Physiologic mechanisms linking physical activity and energy balance

Increased physical activity and less physical inactivity raises total energy expenditure, allowing individuals to consume more calories without gaining weight. There are several lines of evidence to indicate that individuals with 'a low energy output syndrome' are at an increased risk of weight gain and obesity, irrespective of whether this is caused by a genetically determined low resting metabolic rate 9 , by low levels of fidgeting or by an environmentally determined low level of physical activity 10 . Athletes with very high levels of physical activity may have the opposite problem difficulty in ingesting enough calories to replenish and maintain body energy and fat stores.

Performance in cold conditions

As mentioned in the introduction most of the energy liberated during physical exercise is converted to heat. Depending on the metabolic rate, the prescriptive zone and upper and lower critical temperature shifts (see Fig. 2.3.4) and the physiologic mechanisms for heat loss and heat conservation are taxed to varying degrees, depending on how the heat balance is attained. Therefore, some benefits for exercise and performance are obtained in cooler environments. In submaximal cycling at ambient temperatures of 4, 11, 21 and 31 C, the time to exhaustion was longest at 11 C and shortest at 31 C, demonstrating that the effect of ambient temperature on exercise capacity follows an inverted U-shaped relationship 21 . This study demonstrates that exercise capacity is greater in low suprazero ambient temperatures than at higher temperatures, where the physiologic load on the circulatory system is higher. The ambient temperatures in winter sports are usually below the freezing point and...

Energy sources during exercise in the trained state

It is known that increased fat oxidation with training is a local effect since after one-leg training it occurs in the trained leg only 54,55 . Underlying this training response is an increased mitochondrial density and an increased content of mitochondrial enzymes in aerobi-cally trained muscle, accompanied by increases in the enzymes involved in activation, transfer into the mitochondria and b-oxidation of fatty acids 56-58 . Hol-loszy and coworkers have formulated a hypothetical biochemical mechanism whereby a large concentration of mitochondrial oxidative enzymes in trained muscle would lead to a greater reliance on fat metabolism, a lower rate of lactate formation and sparing of muscle glycogen during exercise 57 . These adaptations in trained skeletal muscle would, at a given exercise intensity, permit the rate of fatty acid oxidation to be higher in the trained than in the untrained muscle, even in the presence of a lower intracellular fatty acid concentration in the trained...

Energy sources during exercise in the postabsorptive state

During exercise, the energy consumption may be increased by 20-fold. The primary factor determining whether carbohydrates or fat are preferentially used during exercise is the exercise intensity, the proportion of energy derived from carbohydrates growing progressively larger with increasing intensity. At a moderate exercise level of 100 W, demanding an oxygen uptake of around 1.5 L min, equalling an energy expenditure of 1800 kJ h, the proportions might typically change to 60 carbohydrates and 40 fat. In this situation, the demand for carbohydrates (65 g glucose h, i.e. 1080 kJ) is met by glycogenolysis (around 40-45 g h) and glucose uptake (around 20 g h), whereas the demand for fat is met by lipolysis in adipose tissue and muscle, supplying 18 g fatty acids (i.e. 720 kJ). Under normal circumstances, protein is not an important metabolic fuel during exercise, and it is considered unlikely that, even during prolonged exercise, protein oxidation can cover more than 10 of the energy...

General Signs and Symptoms

Hypoperfusion of skeletal muscles leads to fatigue, weakness, and exercise intolerance. Decreased perfusion of the CNS is related to confusion, hallucinations, insomnia, and lethargy. Peripheral vasoconstriction due to SNS activity causes pallor, cool extremities, and cyanosis of the digits. Tachycardia is also common in these patients and may reflect increased SNS activity. Patients will often exhibit polyuria and nocturia. Polyuria is a result of increased release of natriuretic peptides caused by volume overload. Nocturia occurs due to increased renal perfusion as a consequence of reduced SNS renal vasoconstrictive effects at night. In chronic severe HF, unintentional weight loss can occur which leads to a syndrome of cardiac cachexia. Cardiac cach-exia can be defined as a nonedematous weight loss greater than 6 of the previous normal weight over a period of at least 6 months. HF prognosis worsens considerably once cardiac cachexia has been diagnosed, regardless of HF severity....

Controlling BP in the acute stroke phase

The theory that elevated systemic BP may compensate for the decreased cerebral blood flow in the ischemic region led to attempts to elevate blood pressure as a treatment for acute ischemic stroke. The hemody-namic and metabolic impact of pharmacologically increased systemic blood pressure on the ischemic core and penumbra was evaluated in rats. The mild induced hypertension was found to increase collateral flow and oxygenation and to improve cerebral metabolic rate of oxygen in the core and penumbra 12 . Several small studies in humans have addressed this question and administered vasopressors, including phenylephrine and norepinephrine, to patients with acute stroke 13-15 . Despite a documented improvement in CBF 16 , the concept was abandoned because of the increased risk of hemorrhage and brain edema. In a systemic review of 12 relevant publications including 319 subjects, the small size of the trials and the inconclusive results limit conclusion as to the effects on outcomes, both...

Effects of testosterone on cardiovascular risk factors

Clinical studies indicating that therapeutically-induced changes in HDL-C may not necessarily be accompanied by changes in cardiovascular risk (Hersberger and von Eckardstein 2003). Fifth, testosterone can exert its metabolic effects directly or by its metabolites estradiol and dihydrotestosterone. The effects of testosterone and estradiol, in particular, can be either additive (for example on Lp(a)) or counteractive (for example on HDL-C). Sixth, polymorphisms in the genes of the androgen and estrogen receptors, sex hormone binding globulin (SHBG), 5a-reductase and aromatase, regulate genomic effects and the bioavailability of testosterone, dihy-drotestosterone and estradiol, respectively. Thus, at a given serum concentration the bioactivity and metabolic effects of testosterone can be diverse.

Disorders of Breathing

In addition to symptoms related to loss of sleep or upper airway obstruction, sleep apnea can contribute to other major causes of morbidity and mortality. Bradyarrhythmias are common, and hypoxia can lead to ventricular arrhythmias or even myocardial ischemia or stroke. When episodic hypoventilation becomes frequent or chronic, with resultant hypoxia and hypercapnia, a metabolic response may counteract the respiratory acidosis associated with hypoventilation the kidneys retain bicarbonate to foster a compensatory metabolic alkalosis. Systemic and pulmonary hypertension may be intermediate outcomes that lead to more serious cardiac complications.

Progressive Infantile Poliodystrophy Alpers Disease

Because there is no one pathognomonic clinical sign or laboratory study, Alpers' disease is a diagnosis of exclusion. Therefore, all rapidly progressive infantile encephalopathies need to be excluded by clinical story and or laboratory tests. Measurement of amino acids, organic acids, lactate, and pyruvate should be done in CSF as well as in blood. Mitochondrial biochemical and DNA studies should be performed, looking specifically for the MERRF mutation, as well as functional neuroimaging studies (i.e., MR spectrometry, single photon emission computed tomography SPECT , and PET if available), to garner evidence for defective energy metabolism and oxidative phosphorylation and to determine the biochemical geography. In Alpers' disease electroencephalograms (EEGs) are markedly abnormal, showing a diffuse encephalopathy. A characteristic electroencephalographic pattern consists of high-voltage, very slow delta waves mixed with low-voltage polyspikes. Serial visual evoked...

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